Lung-Metastatic-Patient Information

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Non-Small Cell
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Metastatic
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Metastatic Non-Small Cell Lung Cancer
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Metastatic Non-Small Cell Lung Cancer, 2021 1
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Metastatic Non-Small Cell Lung Cancer
Contents
6 Lung cancer basics
11 Tests for metastatic lung cancer
20 Treatment of driver mutations
30 Treatment by PD-L1 level
37 Treatment by cell type
46 Making treatment decisions
54 Words to know
58 NCCN Contributors
59 NCCN Cancer Centers
60 Index

1
Lung cancer basics
7 Types of lung cancer
8 Lung cancer stages
8 Metastatic lung cancer
10 Review

1 Lung cancer basics Types of lung cancer
Lung cancer starts in the cells of the Lung cancer is a cancer of lung cells. Other
lungs. Non-small cell lung cancer is cancers that have spread to the lung are not
the more common type of lung cancer. lung cancers. For example, breast cancer that
Read this chapter to learn more about has spread to the lungs is still breast cancer.
lung cancer, including metastatic lung
cancer. Lung carcinomas
Almost all lung cancers are carcinomas.
Carcinomas are cancers of cells that line
the inner or outer surfaces of the body. Lung
Types of lung cancer carcinomas form from cells that line the
airways of the lungs. The airways of the lungs
The lungs are the main organs of the are called the bronchus, bronchioli, and alveoli.
respiratory system. They deliver oxygen to Lung carcinomas are divided into 2 groups
the blood and remove carbon dioxide from the based on how the cells look.
blood. The transfer of these gases in and out
of the body is called respiration. Small cell lung cancer (SCLC)
Non-small cell lung cancer (NSCLC)
Airways of the lungs
Air moves through your body

in a series of airways. It travels
down your throat and through the
windpipe (trachea). The windpipe
splits into 2 airways called bronchi.
Inside the lung, each bronchus
branches off into the parts of
the lung, called lobes. The right
lung has 3 lobes, and the left
lung has 2 lobes. The bronchi
divide into smaller airways called
the bronchioli. At the end of the
bronchioli are sacs called alveoli.
Oxygen is transferred from air into
the blood in the alveoli.

1 Lung cancer basics Lung cancer
cancer stages
stages| Metastatic lung cancer
Non-small cell lung cancer of cancer cells in mucus and no detection of a

NSCLC is much more common than SCLC. lung tumor.
There are 3 main types of NSCLC.
Stage 0
Adenocarcinoma
Stage 0 is rare. Abnormal or cancer cells
Squamous cell carcinoma have formed in the airways but haven’t grown
into the lung tissue. Stage 0 is also called
Large cell carcinoma
carcinoma in situ.
Adenocarcinoma is the most common lung
cancer. It often forms from cells that line the Stages 1 through 3
alveoli and make mucus. Squamous cells line Stage 1, stage 2, and stage 3 cancers have
the bronchi. Large cell carcinoma forms from grown into lung tissue. Some have spread to
any of the large cells that are throughout the nearby disease-fighting tissue called lymph
airways. nodes. These cancers have not spread to body
parts far from the lung tumor.
Stage 4
Lung cancer stages To be stage 4, lung cancer must have already
spread far by the time of diagnosis. Lung
The stage of the cancer describes the extent of
cancer tends to travel to the brain and adrenal
the cancer in the body. Doctors use it for many
gland and from one lung to the other lung.
things. It is used to assess the outlook of your
Most lung cancers are stage 4.
cancer called the prognosis. It is used to plan
the right treatment. It is also used for research.
For some people, cancer staging is done

twice. The staging assigned before any tissue
Metastatic lung cancer
(biopsy) testing is called the clinical stage. The
The spread of cancer is called metastasis.
second staging is called the pathologic stage
When lung cancer has spread far from the first
and is based on tissue tests. Cancer that is
lung tumor, it is called metastatic lung cancer.
outside of the lungs may not be found until
after surgery.
After diagnosis, stage 1, stage 2, or stage 3
lung cancer may metastasize to body parts
Staging system far from the lung tumor. Stage 4 lung cancer
The American Joint Committee on Cancer is metastatic lung cancer at diagnosis. This
(AJCC) staging manual is used to stage lung book discusses treatment for metastatic lung
cancer. The stages of NSCLC range from cancers.
stage 0 to stage 4. Often, the stages are
written with Roman numerals—stages 0, I, II, Learn more about stage 1 through 3 lung
III, and IV. Occult carcinoma is a rare finding cancers that have not spread far in NCCN
Guidelines for Patients: Early and Locally

1 Lung cancer basics Metastatic lung cancer
Advanced Non-Small Cell Lung Cancer, Symptoms

available at NCCN.org/patientguidelines. Symptoms caused by metastatic NSCLC
depend on where it is. Some signs and
symptoms of metastatic lung cancer are:
Trouble breathing, chronic cough, and

chest pain
Pain in bone or spine
Yellowing of the skin or eyes called
jaundice
Constant feeling of a full stomach
Headaches, dizziness, or seizures
Weakness or numbness of arms or legs
Fatigue and unexplained weight loss
Metastatic lung
cancer
Lung cancer that has spread

far from the main lung tumor
is called metastatic lung
cancer. All lung cancers that
have spread outside the
chest are metastatic lung
cancers. Within the chest,
distant sites include the
tissue lining or fluid around
a lung or heart. Lung cancer
that has spread from one
lung to the other lung is also
metastatic lung cancer.

1 Lung cancer basics Review
Treatment Review
Metastatic lung cancer is not often treated
with local treatment. Local treatment includes The lungs help the body get the air it
surgery, radiation therapy, and chemoradiation. needs to live.
It may be an option if metastases are limited.
The lungs are made of many small
An example is cancer spread to only the brain
airways and sacs.
or adrenal gland. Local treatments may also be
used to reduce (palliate) symptoms caused by Lung cancer often starts in the cells that
a metastasis. line the airways. These cancers are called
carcinomas.
Most often, systemic therapy is used to treat
Lung cancer more often affects the
metastatic lung cancer. Systemic therapy
larger cells of the lungs. These cancers
affects all cancer in the body. It can treat
are called non-small cell lung cancer
widespread metastases. Medical oncologists
(NSCLC).
are cancer doctors trained to use systemic
therapy. The focus of this book is systemic The cancer stage is a rating of the extent
therapy for metastatic lung cancer. of the cancer. Stages of lung cancer
range from stage 0 to stage 4.
At this time, metastatic lung cancer is unlikely
Metastatic lung cancer has spread far
to be cured. The aim of treatment is to reduce
from where it started. It includes stage 1
symptoms, control the cancer, and extend
through 3 lung cancers that have spread
life. Newer treatments are better at controlling
far after diagnosis. It also includes all
the cancer and improving quality of life. Your
stage 4 lung cancers.
doctor will tailor treatment to you based on
tests described in Chapter 2. Most often, systemic therapy is used to
treat metastatic lung cancer. Systemic
therapy affects all cancer in the body.
Treatment team
A team of health care providers is involved in There are newer treatments for metastatic
diagnosing and treating lung cancers. Your lung cancer that better control the cancer
primary doctor may be the first to suspect you and improve quality of life.
have lung cancer and refer you to specialists.
A team of experts will work together with
The diagnostic, treatment, and supportive
you to diagnose and treat the cancer as
care experts are explained throughout this
well as support you.
book. These experts are supported by nurses,
technicians, and assistants, who are often on
the frontline of cancer care. Patient navigators
can help you through the maze of cancer care.

2
Tests for metastatic lung
cancer
12 Health history and exam 18 Supportive care
14 Blood tests 19 Review
14 Imaging
15 Biopsy vs. surgery
16 Cancer cell tests
17 Biomarker tests
18 Lung function tests

2 Tests for metastatic lung cancer Health history and exam
Not all metastatic lung cancers are the Health history and exam
same. It is important to get the right
tests to learn about the cancer and your Your cancer doctors need to have all of your
health. Read this chapter to learn what health information. A complete report of your
tests and other health care are needed health is called a medical history. Your doctor
before treatment. will also perform a physical exam of your body.
An exam is done to find signs of disease and
decide which treatments may be options. See
Guide 1 for a list of tests used for metastatic
lung cancer.
Guide 1
Health tests and services for metastatic lung cancer
• Medical history
• Current or past smoking
Health history and exam • Weight loss
• Physical exam
• Performance status
• CBC with differential

Blood tests
• Chemistry profile
• Diagnostic CT of the chest and upper abdomen

Imaging • FDG PET/CT
• Brain MRI
• Biopsy to remove tissue sample

Cancer cell tests • Pathology review to assess for cancer and learn cancer cell type
• Biomarker testing
• Spirometry
Lung function tests • Gas diffusion test
• Body plethysmograph
• Smoking treatment
Services
• Supportive care

2 Tests for metastatic lung cancer Health history and exam
Medical history Family history

Your doctor will ask about any health problems Be prepared to discuss the health problems
and treatments during your lifetime. When you of your close blood relatives. Such family
meet with your cancer doctors, be ready to talk members include brothers, sisters, parents,
about: and grandparents. Some cancers and other
health conditions can run in families.
Illnesses
Injuries Physical exam
Cancer can spread to lymph nodes and cause
Health conditions
them to swell. Your doctor will gently press
Symptoms on your body to assess their size. There are
lymph nodes all over your body. Lung cancer
Medications
often spreads to nodes in the chest and neck.
Your doctor will ask about symptoms that may
During this exam, also expect the following to
be related to lung cancer. Such symptoms
be checked:
include cough, trouble breathing, chest pain,
and weight loss. Early stages of lung cancer
Your body temperature
may not cause symptoms. Symptoms in late
stages depend where the cancer is. Your blood pressure
Your pulse and breathing rate
Smoking
Your weight
You can get lung cancer even if you never
smoked. If you have lungs, you can get lung How your lungs, heart, and gut sound
cancer. Your doctors will ask about current and
How your eyes, skin, nose, ears, and
past smoking to plan treatment.
mouth look
Tell your doctors if you smoke or have smoked The size of your organs
in the past. Smoking is often measured by
Level of pain when you are touched
packs per day and the number of years that
you have smoked.
Performance status
If you do smoke, it is important to quit. Based on your history and exam, your doctor
Smoking can limit how well cancer treatment will rate your performance status. Performance
works. Nicotine addiction is one of the hardest status is your ability to do day-to-day activities.
addictions to stop. The stress of having cancer Doctors use it to assess if you can undergo
may make it harder to quit. There is help. Ask certain treatments.
your health care providers about counseling
and drugs to help you quit.

2 Tests for metastatic lung cancer Blood tests
Blood tests assesses if the chemicals in your blood are too

low or high. Abnormal levels can be caused by
Blood tests measure blood cells, proteins, and spread of cancer or by other health problems.
chemicals in the bloodstream. A blood draw
removes a sample of blood for testing. It is
done with a needle inserted into a vein. You
may need to fast from food and most liquids for Imaging
hours before the draw.
Imaging makes pictures of the insides of your
body. It can show cancer in deep tissue, lymph
CBC with differential
nodes, or distant body parts. A radiologist is a
If not done recently, a complete blood count
doctor who’s an expert in reading images. This
(CBC) with differential is needed. A CBC
doctor will convey the test results to your other
measures parts of the blood including counts
doctors.
of white blood cells, red blood cells, and
platelets. A differential measures the counts of
Your doctors will use imaging results to plan
each type of white blood cell and checks the
where to biopsy and which treatment is best.
balance of the counts. Cancer and other health
Scans that were done more than 60 days ago
problems can cause low or high blood counts.
should not be used to decide your treatment.
Chemistry profile
Chemicals in your blood come from your liver,
bone, and other organs. A chemistry profile
Imaging
Pictures of the insides of

your body can be made with
imaging. During the scan, you
will lie on a table that will move
into the tunnel of the machine.
The pictures will be viewed
by a doctor who will look for
signs of cancer.

2 Tests for metastatic lung cancer Biopsy vs.
Diagnostic CT Biopsy vs. surgery

Computed tomography (CT) makes a more
detailed image than a plain x-ray. It takes many To diagnose lung cancer, a biopsy or surgery is
pictures of your body from different angles used to remove bits of tissue for testing. Often,
using x-rays. A computer then combines the tissue from the metastasis is removed rather
pictures to make a 3-D image. than from the lung tumor. The tissue must be
large enough to run several special lab tests.
A diagnostic CT involves a higher dose of
radiation and contrast. Contrast is a substance Your doctor may try to diagnose and stage the
that is often injected into the bloodstream. It cancer at the same time. The body part that
makes the images easier to read. For cancer likely has cancer and is farthest from the lung
staging, images of your chest and upper tumor will be sampled and tested. By doing
abdomen are needed. this, you’ll have fewer procedures.
Your doctor will use imaging results to select

FDG PET/CT
the biopsy site. This site is often the adrenal
You will also need a PET/CT scan. PET is
gland, liver, or bone. The type of biopsy that
short for positron emission tomography. A
will be done depends on the site.
PET/CT scan may detect cancer that was not
found by CT alone.
External needle biopsies involve guiding
a thin needle through your skin and
PET detects cancer with a radioactive sugar
into the tumor. These biopsies include
and special camera. The radioactive sugar,
transthoracic needle aspiration (TTNA),
called fluorodeoxyglucose (FDG), will be
core needle biopsies, pericardiocentesis,
injected into your vein.
and thoracentesis.
Cancer quickly uses sugar so it appears Down-the-throat biopsies involve
“hot” in images. Other health problems can guiding tools down your throat into your
also cause hot spots, too. Cancer detected windpipe or esophagus. These biopsies
by PET/CT often needs to be confirmed with include radial endobronchial ultrasound
biopsy or other imaging. (EBUS) bronchoscopy and endoscopic
ultrasound (EUS)-guided biopsies.
Brain MRI Portal surgeries involve making small
Magnetic resonance imaging (MRI) uses openings (ports) into your chest. Small
a magnetic field and radio waves to make tools are inserted through the ports to
pictures. Contrast should be used. If you have remove tissue. These surgeries include
or may have metastatic lung cancer, brain MRI thoracoscopy.
is very important. It will show if the cancer has
Open surgery involves making a larger
spread to your brain.
cut through your chest wall to remove
tissue. You may have open surgery when
other methods won’t work or a larger
piece of tissue is needed.

2 Tests for metastatic lung cancer Cancer cell tests
Cancer cell tests

Diagnosis
Tissue removed during biopsy or surgery
is sent to a doctor called a pathologist.
Pathologists are experts in tissue and cells It takes a team to decide the best steps to
and diagnosing cancer. In a lab, a pathologist
diagnose lung cancer. Removing tissue for
will look at the tissue with a microscope. If
cancer testing is not always easy. Your team
lung cancer is found, more tests will be done
may include the following experts:
because not all lung cancers are alike. Lung
cancer differs by cell type and how the cells
are abnormal. • Thoracic radiologist
• Interventional radiologist
Lab results used for diagnosis are included in
a pathology report. This report will be sent to • Thoracic surgeon
your cancer doctor. Ask for a copy. It is used to • Interventional pulmonologist
plan your treatment. Your doctor will review the
results with you. Take notes and ask questions.
When planning, doctors think about the size
and location of tumors, your health history,
The pathologist will study the tumor to classify
and their experience. They rely on the results
the disease. This is called histologic typing.
The pathology report will state if the cancer of the physical exam and imaging.
started in the lung or elsewhere. If the cancer
started in the lung, the report will also list the Test results will determine your treatment
type of lung cancer. Cell (histologic) types of plan. Ask questions about and keep copies of
lung cancer include: all your test results.
Adenocarcinoma
Large-cell lung carcinoma
Squamous cell carcinoma
Small cell carcinoma
Mixed and rare types

2 Tests for metastatic lung cancer Biomarker tests
Biomarker tests become cancer cells and support cancer

growth. Typically, cancer cells do not have
Lung cancer differs between people by cell more than one driver mutation.
type but also by abnormal cell changes.
Changes in cancer cells affect treatment PD-L1 is a protein on the surface of cells.
options and are called biomarkers. Because of PD-L1 on cancer cells stops T cells from killing
biomarkers, a treatment that helps one person them. The cancer cells survive and make more
might not help you. See Guide 2 for a list cancer cells.
of biomarkers and which cancers should be
tested for them. Most lung cancers do not have a known
biomarker for which there is treatment.
For lung cancer, there are 2 groups of Treatment options for these cancers are based
biomarkers. on the lung cell type. Very few squamous cell
carcinomas have a driver mutation. Biomarker
Driver mutations testing may be done if you’ve never smoked
or the cancer is a mix of cell types. All lung
PD-L1
cancers should be tested for PD-L1.
Driver mutations are also called driver
Most often, biomarker testing is performed on
oncogenes. They cause normal cells to
tissue from the tumor. It is not the same as
Guide 2
Biomarker testing
Adenocarcinoma, large
Squamous cell lung cancer
cell, and rare lung cancers
Driver mutation
Sensitizing EGFR mutations ● ●
ALK rearrangement ● ●
ROS1 rearrangement ● ●
BRAF V600E mutation ● ●
NTRK gene fusion ● ●
MET exon 14 skipping ● ●
RET rearrangement ● ●
Cell protein
PD-L1 ● ●
● Testing is recommended ● Testing if needed

2 Tests for metastatic lung cancer Lung function tests | Supportive care
genetic testing, which assesses what a person Supportive care

inherited from their parents.
Supportive care aims to improve your quality of
A second biopsy may be needed if the first life. It is also sometimes called palliative care.
tissue sample is too small. Sometimes, a Supportive care is important for everyone,
sample of blood may be used for biomarker not just people at the end of life. In fact, it has
testing. A blood sample is referred to as a been shown to extend and enhance life for
“liquid biopsy.” people with metastatic lung cancer.
Broad molecular profiling of all biomarkers is Supportive care can address many needs. It
advised. There are other known biomarkers includes care for health problems caused by
linked with lung cancer. However, they are rare cancer or cancer treatment. You can get help
and related treatments are still being tested in with making treatment decisions. You can get
clinical trials. help with coordination of care between health
providers.
Your palliative care doctor will work with your

Lung function tests oncologists to provide you the best care. Other
specialists who may be involved in your care
Surgery or radiation therapy may be treatment include:
options for some metastatic cancers. First,
your doctors will need to know how well your Respiratory therapists
lungs work. There are 3 pulmonary tests that
Rehabilitation specialists
may be used to assess your lungs:
Registered dieticians
Spirometry involves blowing into a tube to
Social workers
measure how much air and how fast you
breathe.
A gas diffusion test involves breathing in
a harmless gas and measuring how much
you breathe out. It tells how much oxygen
travels from your lungs into your blood.
Body plethysmograph involves sitting in a
small room and breathing into a tube. This
test measures how much air your lungs
can hold and how much air is left in your
lungs after you exhale.

2 Tests for metastatic lung cancer Review
Review Pulmonary function tests are needed if

surgery or radiation therapy will be used
To plan treatment, your doctors need to for treatment.
learn about the cancer and your health.
Start supportive care early. It has been
Be ready to tell your doctors about any shown to extend and enhance life for
health problems and treatments you’ve people with metastatic lung cancer.
had in your lifetime.
Ask your doctor for help to quit smoking.
Quitting may improve treatment results.
Your doctors will examine your body for
signs of disease. The exam will include
touching parts of your body to see if
anything feels abnormal.
Your doctors will rate your ability to do
day-to-day activities in order to decide
your treatment options.
Your doctors will order blood tests. Blood
tests are used to look for signs of cancer.
Diagnostic CT can help show where the
cancer has spread. PET/CT may detect
cancer that CT did not. MRI is used to see
if the cancer has spread to your brain.
A biopsy is needed to confirm that there
is cancer. Doctors use imaging to decide
what tissue should be removed and how
best to remove it. Often, samples from the
adrenal gland, liver, or bone are removed.
A pathologist will study your tissue
samples with a microscope. If there is
cancer, the pathologist will identify the
type of cell from which the cancer formed.
Metastatic lung cancer should be tested
for biomarkers to identify what is the best
treatment for you. A treatment that helps
one person might not help you. Most lung
cancers do not have a known biomarker.

3
Treatment of driver mutations
21 Driver mutations
22 Targeted therapy
22 Sensitizing EGFR mutations
24 ALK rearrangement
26 ROS1 rearrangement
26 BRAF V600E mutation
27 MET exon 14 skipping
28 Side effects
29 Review

3 Treatment of driver mutations Driver mutations
Driver mutations promote the growth of parts. Abnormal changes in genes are called
cancer. They are most often found in mutations.
adenocarcinomas and mixed cell types
of lung cancer. Targeted therapy of A driver mutation causes normal cells to
lung cancer stops the effects of driver become cancer cells. It enables the cancer
mutations. cells to quickly duplicate, survive, and spread
in the body. There are different types of driver
mutations. Driver mutations are detected
by biomarker testing of cancer cells and not
Driver mutations genetic testing, which assesses inherited
changes from parent to child.
Genetic information tells your cells what to do.
In lung cancer, a common driver mutation is a
It is located in the nucleus of a cell and stored
gene rearrangement. A gene rearrangement
in 46 long strands of DNA. A gene is a small
is also called a gene fusion. This term refers
segment of DNA. DNA strands are carried and
to one part of a gene switching places (fusing)
protected in 23 chromosomes.
with a part from another gene. The gene fusion
produces an abnormal protein that promotes
Abnormal changes in genetic information
cancer growth.
often occur in cancer cells. The DNA can be
broken, missing, rearranged, or have extra
Genetic information
The nucleus is the control

center or “brain” of cells.
Within the nucleus is genetic
information that tells the cells
what to do. The information is
stored in DNA. DNA looks like
a twisted ladder when uncoiled
from a chromosome. Genes are
segments of DNA that contain
“instructions” for the cell.
Abnormal changes in genes
that promote cancer growth are
called driver mutations.

3 Treatment of driver mutations Targeted therapy | EGFR mutations
Targeted therapy biomarker test results. If a driver mutation is

found, you have two options:
Targeted therapy is used to treat driver
mutations of lung cancer. It treats cancer by You may stop your current treatment early
stopping the specific ways by which cancer and start targeted therapy.
cells live, survive, and die. It harms fewer
The other option is to finish your current
types of normal cells than chemotherapy,
treatment (including the last phase called
which destroys any type of fast-growing cell.
maintenance treatment), and then start
targeted therapy.
Kinase inhibitors
The most common type of targeted therapy for
lung cancer is kinase inhibitors. They are pills
that can be taken at home. Sensitizing EGFR mutations
Kinases are a type of cell protein. They are A surface receptor called EGFR can be
part of many chemical pathways, some of overactive causing lung cells to quickly grow.
which start cell growth. They are often part of Mutations in the gene that controls EGFR
a structure called a surface receptor. Surface are common. Sensitizing mutations are the
receptors are on the outer membrane of a cell. ones that cause overactive EGFR. First-
They start changes within the cell when turned line treatment options for sensitizing EGFR
on. mutations are listed in Guide 3.
Kinases change the action of other proteins

by attaching phosphates to them. Kinase
inhibitors stop cell growth signals by blocking Guide 3
the transfer of phosphates. This lowers the First-line treatment of sensitizing
number of new cancer cells being made. EGFR mutations
Preferred options
VEGF antibodies
• Osimertinib
Cancer cells need blood to grow, so they
release a protein called VEGF. VEGF triggers
endothelial cells to form new blood vessels Other options
on tumors. VEGF antibodies stop VEGF, • Erlotinib
and the cancer cells die from a lack of blood. • Afatinib
You will need to go to a health care center to • Gefitinib
receive VEGF antibodies through a slow drip • Dacomitinib
(infusion). • Erlotinib and ramucirumab
• Erlotinib and bevacizumab
Switching to targeted therapy
You may have started a treatment different
than targeted therapy before getting

3 Treatment of driver mutations Sensitizing EGFR mutations
First-line treatment After first-line treatment

Erlotinib (Tarceva ) and gefitinib (Iressa ) were
® ®
Within a few years on first-line treatment, lung
the first EGFR inhibitors used to treat lung cancer starts to grow again in most people.
cancer. The second group of EGFR inhibitors You may get a biopsy:
to be developed were afatinib (Gilotrif®) and
dacomitinib (Vizimpro®). The newest EGFR If the cancer grows while on erlotinib,
inhibitor is osimertinib (Tagrisso®). afatinib, gefitinib, or dacomitinib, testing
for a T790M mutation is advised. The
All EGFR inhibitors have been found to work T790M mutation in the EGFR gene often
well in well-designed clinical trials. Osimertinib occurs after taking these drugs. It stops
is preferred because it stops cancer growth for the cancer drugs from working. A liquid
a longer period of time. If your first treatment biopsy should be tried before a tumor
was immunotherapy, a short delay in starting biopsy is done.
osimertinib may be needed to prevent health
To rule out transformation to small cell
problems.
lung cancer, you may get a biopsy.
Erlotinib is sometimes combined with a
Treatment options depend on how the cancer
VEGF antibody. VEGF antibodies include
worsens. Your doctor will check for symptoms
bevacizumab (Avastin®) and ramucirumab
and if the cancer has spread to more places.
(Cyramza®). It is not safe to receive
Options are listed in Guide 4.
bevacizumab if you are coughing up blood
(hemoptysis).
Guide 4
Options after first-line treatment for sensitizing EGFR mutations
Local treatment of limited tumors may be helpful for some people
Stay on first-line treatment if it has some benefit

• Stay on erlotinib, afatinib, gefitinib, or osimertinib unless the cancer is widespread
• Stay on dacomitinib unless the cancer is in the brain or widespread
Switch to a different targeted therapy

• Switch to osimertinib if the lung cancer cells have a T790M mutation
• Switch to afatinib with cetuximab if cancer worsens while taking osimertinib
Start treatment for cell type as listed in Chapter 5

3 Treatment of driver mutations ALK rearrangement
If the cancer is not widespread, your doctor ALK rearrangement

may recommend local treatment. It is used to
treat cancer in a specific place like the brain A surface receptor called ALK can be
or adrenal gland. In addition, EGFR inhibitors overactive causing lung cells to quickly
will be used to control cancer growth. The type grow. The cause of ALK overactivity is a
of local treatment received differs between rearrangement of the ALK gene. First-line
people: treatment options for ALK rearrangements are
listed in Guide 5.
Stereotactic radiosurgery (SRS) for brain
tumors There are 5 ALK inhibitors used to treat lung
cancer. Crizotinib (Xalkori®) was the first ALK
Surgery
inhibitor used to treat lung cancer. The second
Stereotactic ablative radiotherapy (SABR) group of ALK inhibitors to be developed were
ceritinib (Zykadia®), alectinib (Alecensa®), and
Image-guided thermal ablation therapy if
brigatinib (Alunbrig®). The newest ALK inhibitor
radiation therapy is not safe
is lorlatinib (Lorbrena®).
Despite the cancer worsening, first-line
treatment may be slowing down cancer After first-line treatment
growth. If this treatment is stopped, the cancer Within a few years of starting first-line
may worsen quicker. Staying on first-line treatment, lung cancer starts to grow again
treatment may be an option if the cancer isn’t in most people. Treatment options depend
widespread. Your doctor may not keep you on on how the cancer worsens. Your doctor will
dacomitinib if the cancer has spread to your
brain. There is no research on dacomitinib for
brain metastases. Guide 5
First-line treatment of ALK
If first-line treatment stops working, switching rearrangement
to a different targeted therapy may be an
option. Your doctor may switch your treatment Preferred options
to osimertinib if the lung cancer cells have a
• Alectinib
T790M mutation.
• Brigatinib
• Lorlatinib
Your doctor may switch treatment to afatinib
and cetuximab if you were taking osimertinib.
Cetuximab stops growth signals from EGFR by Other options
attaching to EGFR on the outside of cells. It is • Ceritinib
received by infusion.
Sometimes useful
If targeted therapy is not likely to help, your • Crizotinib
doctor may recommend other treatment.
Treatment used for cell type may be an option.
See Chapter 5.

3 Treatment of driver mutations ALK rearrangement
check for symptoms and order tests to see may worsen quicker. Staying on first-line
if the cancer has spread to more places. treatment may be an option if the cancer isn’t
Treatment options are listed in Guide 6. widespread. Crizotinib doesn’t work if the
cancer has spread to your brain. The other
If the cancer is not widespread, your doctor ALK inhibitors work better in the brain.
may recommend local treatment. Local
treatment is used to treat cancer in a specific If first-line treatment stops working, your
place like the brain or adrenal gland. In treatment may be switched to a newer ALK
addition, ALK inhibitors will be used to control inhibitor. Treatment may be switched to
cancer growth. The type of local treatment lorlatinib if you’re on alectinib, brigatinib, or
received differs between people: ceritinib. If on crizotinib, treatment may be
switched to alectinib, brigatinib, ceritinib, or
SRS for brain tumors lorlatinib.
surgery
If ALK inhibitors are not likely to help, your
SABR doctor may advise other treatment. Treatment
used for cell type may be an option. See
image-guided thermal ablation therapy if
Chapter 5.
radiation therapy is not safe
Despite the cancer worsening, first-line

treatment may be slowing down cancer
growth. If this treatment is stopped, the cancer
Guide 6
Options after first-line treatment of ALK rearrangement
Local treatment of limited tumors may be helpful for some people
Stay on first-line treatment if it has some benefit

• Stay on alectinib, brigatinib, ceritinib, or lorlatinib unless the cancer is widespread
• Stay on crizotinib unless the cancer is in the brain or widespread
Switch to a newer ALK inhibitor

• Switch to lorlatinib if on alectinib, brigatinib, or ceritinib
• Switch to alectinib, brigatinib, ceritinib, or lorlatinib if on crizotinib
Start treatment for cell type as listed in Chapter 5

3 Treatment of driver mutations ROS1 rearrangement | BRAF V600E
ROS1 rearrangement BRAF V600E mutation

A surface receptor called ROS can be A signaling protein inside of cells called BRAF
overactive causing lung cells to quickly can be overactive causing lung cells to quickly
grow. The cause of the overactivity is a gene grow. It is overactive due to a BRAF V600E
rearrangement. Treatment options for ROS1 mutation. Treatment options for BRAF V600E
rearrangements are listed in Guide 7. mutation are listed in Guide 8.
Entrectinib (Rozlytrek®) and crizotinib (Xalkori®) Preferred treatment is dabrafenib plus

are preferred options. Entrectinib may work trametinib. Dabrafenib (Tafinlar®) stops growth
better for lung cancer in the brain. The other signals from BRAF. MEK is a protein within the
option is ceritinib (Zykadia®). same signaling pathway as BRAF. Trametinib
(Mekinist®) stops growth signals from MEK.
In time, the cancer will worsen after first-line
treatment. Lorlatinib (Lorbrena®) may be an If dabrafenib plus trametinib makes you too
option after first-line treatment. Entrectinib may sick, you may receive vemurafenib (Zelboraf®).
be an option after crizotinib if the cancer has Vemurafenib also stops growth signals from
spread to the spinal cord or brain. Treatment BRAF. If not received before, treatment used
used for cell type may be an option. See for cell type may be an option. See Chapter 5.
Chapter 5.
In time, the cancer will worsen after first-line
treatment. After targeted therapy, treatment
used for cell type may be used to treat lung
cancer. If not used before, dabrafenib plus
Guide 7 trametinib may be started if the cancer
Treatment of ROS1 rearrangement worsens on first-line treatment.
Preferred options
• Entrectinib
First-line • Crizotinib Guide 8
treatment Treatment of BRAF V600E mutation
Other options
• Ceritinib
Preferred options
• Dabrafenib plus trametinib
• Lorlatinib
Options after
• Entrectinib Sometimes useful
first-line
treatment • Treatment for cell type as • Vemurafenib
listed in Chapter 5 • Treatment for cell type as listed in Chapter 5

3 Treatment of driver mutations NTRK gene fusion | MET exon 14 skipping
NTRK gene fusion MET exon 14 skipping

Lung cells have a family of 3 surface receptors Some lung cancers have too much of a
called TRK. NTRK genes contain instructions surface receptor called MET. Too much MET
for making TRK. Some lung cancers have too causes fast cell growth. The cause of excess
much TRK, which causes fast cell growth. The MET is a deleted (skipped) part of the MET
cause of excess TRK is a joining (fusion) of gene called exon 14. Treatment options for
NTRK with another gene. Treatment options MET exon 14 skipping are listed in Guide 10.
for NTRK gene fusion are listed in Guide 9.
MET inhibitors are preferred for first-line
TRK inhibitors are preferred for first-line treatment. These treatments include capmatinib
treatment of people with an NTRK mutation. (Tabrecta™) and tepotinib (Tepmetko®).
These treatments include larotrectinib Crizotinib (Xalkori®) is useful for some people. It
(Vitrakvi®) and entrectinib (Rozlytrek®). These inhibits MET and other kinases. If not received
treatments have not been compared in before, treatment used for cell type may be
research, but entrectinib may work better for an option. Treatment regimens are listed in
lung cancer in the brain. If not received before, Chapter 5.
treatment used for cell type may be an option.
See Chapter 5. In time, the cancer will worsen after first-line
treatment. After targeted therapy, treatment
In time, the cancer will worsen after first-line for cell type may be used to treat lung cancer.
treatment. After targeted therapy, treatment If not used before, targeted therapy may be
used for cell type may be used to treat lung started if the cancer worsens on first-line
cancer. If not used before, a TRK inhibitor may treatment.
be started if the cancer worsens on first-line
treatment.
Guide 9 Guide 10
Treatment of NTRK gene fusion Treatment of MET exon 14 skipping
Preferred options Preferred options

• Larotrectinib • Capmatinib
• Entrectinib • Tepotinib
Sometimes useful
Sometimes useful
• Crizotinib
• Treatment for cell type as listed in Chapter 5
• Treatment for cell type as listed in Chapter 5

3 Treatment of driver mutations Side rearrangement
RET effects | Side effects
RET rearrangement Side effects

A surface receptor called RET can be All cancer treatments can cause unwanted
overactive causing lung cells to quickly health issues. Such health issues are called
grow. The cause of the overactivity is a gene side effects. Some side effects may be harmful
rearrangement. Treatment options for RET to your health. Others may just be unpleasant.
rearrangements are listed in Guide 11.
Side effects depend on many factors. These
RET inhibitors are preferred for first- factors include the treatment type, length or
line treatment. These treatments include dose of treatment, and the person.
selpercatinib (Retevmo™) and pralsetinib
(Gavreto™). Cabozantinib (Cometriq®, Many effects of treatment quickly resolve after
Cabometyx®) and vandetanib (Caprelsa®) treatment ends. Long-term effects start during
are useful for some people. They inhibit RET treatment and persist after treatment is done.
and other kinases but don’t work as well as Less often, effects start long after treatment
preferred treatments. If not received before, has ended.
treatment used for cell type is another option.
See Chapter 5. Ask your treatment team for a complete list
of side effects of your treatments. Also, tell
In time, the cancer will worsen after first-line your treatment team about any new or worse
treatment. After targeted therapy, treatment symptoms you get. There may be ways to help
used for cell type may be an option. If not used you feel better. There are also ways to prevent
before, targeted therapy may be started if the some side effects.
cancer worsens on first-line treatment.
NCCN has a patient guide on late and long-
term effects of cancer and treatment. Such
effects include fatigue, poor sleep, and heart
disease.
Guide 11
Treatment of RET rearrangement Read about
common effects in
Preferred options
NCCN Guidelines
• Selpercatinib
for Patients:
• Pralsetinib
Survivorship
Sometimes useful Care for Cancer-
• Cabozantinib Related Late
• Vandetanib and Long-Term
Effects, available
Other at NCCN.org/
• Treatment for cell type as listed in Chapter 5 patientguidelines.

3 Treatment of driver mutations Review
Review
A driver mutation causes normal cells
to become cancer cells. It enables the
cancer cells to quickly duplicate, survive,
and spread in the body.
Targeted therapy is used to treat driver
mutations of lung cancer. Kinase
inhibitors are the most common type of
targeted therapy of lung cancer.
Some people start treatment before We want your
getting the results of biomarker testing. feedback!
You could stay on your current treatment
then take targeted therapy. A second Our goal is to provide helpful
option is to switch from your current
and easy-to-understand
treatment to targeted therapy.
information on cancer.
For each type of driver mutation there is
at least one preferred targeted therapy Take our survey to let us
and often other regimens. know what we got right and
When targeted therapy is not likely to what we could do better:
help, you may start treatment for cell type.
NCCN.org/patients/feedback
Ask your treatment team for a complete
list of side effects of your treatments.
Also, tell your treatment team about any
new or worse symptoms you get.

4
Treatment by PD-L1 level
31 Immune checkpoints
31 Immunotherapy
32 Treatment options
35 Side effects
36 Review

4 Treatment by PD-L1 level Immune checkpoints | Immunotherapy
Some people have lung cancer cells CTLA-4 and PD-1 are two types of brake
that evade death by T cells. Read this pedals on T cells.
chapter to learn more about this survival
skill of cancer cells. Immunotherapy In people with lung cancer, the brake pedals
restores the killing ability of T cells. on T cells may be overused. CTLA-4 is
activated when attached to B7 on immune
cells called dendritic cells. PD-1 is activated
when attached to PD-L1 on lung cancer cells.
Immune checkpoints With the brakes on, T cells are not able to kill
cancer cells.
The body’s defense against disease is called
the immune system. T cells are a key part of
this system. T cells that kill infected and cancer
cells are called cytotoxic or killer T cells.
Immunotherapy
Immunotherapy is a treatment that uses
The immune system has “brakes” that prevent
the immune system to kill cancer cells.
or slow down an immune response. The
Immune checkpoint inhibitors are a type of
brakes are called immune checkpoints. They
immunotherapy. They work by releasing the
protect the body’s healthy cells. Proteins called
brake pedals on T cells.
Immunotherapy
Some lung cancers consist of cells

that have PD-L1 on their surface.
PD-L1 can attach to PD-1 on T
cells and stop T cells from killing
cancer cells. Immunotherapy
stops PD-L1 from attaching. As
a result, T cells are able to attack PD-1 inhibitor
cancer cells. There are two types
of immunotherapy. PD-1 inhibitors
attach to T cells. PD-L1 inhibitors
attach to cancer cells. PD-L1 inhibitor

4 Treatment by PD-L1 level Treatment options
There are 5 checkpoint inhibitors used to treat take it. For some people, immunotherapy may
metastatic lung cancer: impair their immune system. Tell your doctor
if you have an autoimmune disease, such as
Pembrolizumab (Keytruda®) Crohn’s disease, ulcerative colitis, or lupus.
Bring a list of your medications to your health
Nivolumab (Opdivo®)
care appointments.
Cemiplimab (Libtayo®)
Atezolizumab (Tecentriq®)
Ipilimumab (Yervoy®) Treatment options
These checkpoint inhibitors block proteins Immunotherapy options are partly based
to keep the immune checkpoint turned off. on PD-L1. A pathologist will assess the
Pembrolizumab, nivolumab, and cemiplimab percentage of cancer cells with PD-L1. A
are PD-1 inhibitors. They attach to PD-1 on sample of a lung tumor is needed for testing.
T cells and block PD-L1. Atezolizumab is
a PD-L1 inhibitor. It attaches to PD-L1 on High PD-L1 means that at least half of the
cancer cells so PD-L1 can’t attach to T cells. cancer cells have PD-L1 (50% or more)
Ipilimumab is a CTLA-4 inhibitor. It attaches to
Low PD-L1 means that less than half of
CTLA-4 on T cells and blocks attachment to
cancer cells have PD-L1 (1% to 49%)
B7.
No PD-L1 means that fewer than 1 out of
Checkpoint inhibitors are slowly injected into a 100 cells have PD-L1 (less than 1%)
vein (infusion). It may take 30 or 60 minutes to
get the full dose. Infusions are received every For lung cancer with PD-L1, see Guide 12 for
few weeks. The number of weeks between a list of treatment options for adenocarcinoma,
treatments depends on the inhibitor used. large cell, and rare lung cancer. Treatment
Often, people get infusions until they stop options for squamous cell lung cancer are
working and the cancer worsens. listed in Guide 13. Treatment of lung cancer
with no PD-L1 is discussed in Chapter 5.
Not all lung cancers should be treated with
immunotherapy. Immunotherapy should
First-line treatment
not be the first treatment if the cancer cells
Used alone, PD-1 inhibitors have good results
have cancer-promoting (driver) mutations.
for lung cancer with high PD-L1. Combining
Cancers with driver mutations should first be
PD-1 or PD-L1 inhibitors with chemotherapy
treated with targeted therapy as described
also has good results. It is standard treatment
in Chapter 3. First-line targeted therapy has
when PD-L1 is high or low.
better results and causes less serious health
problems.
Platinum-doublet chemotherapy is used with
checkpoint inhibitors. It consists of cisplatin
Immunotherapy may also not be given if it may
or carboplatin—drugs made with platinum—
be unsafe. Some people may be too sick to
and another type of chemotherapy. Choice of

Guide 12
First-line treatment options by PD-L1 level
Adenocarcinoma, large cell, and rare types of lung cancer
Preferred regimens Low PD-L1 High PD-L1
Pembrolizumab ●
Atezolizumab ●
Cemiplimab ●
Pembrolizumab, carboplatin, and pemetrexed ● ●
Pembrolizumab, cisplatin, and pemetrexed ● ●
Other regimens
Nivolumab, ipilimumab, carboplatin, and pemetrexed ● ●
Nivolumab, ipilimumab, cisplatin, and pemetrexed ● ●
Atezolizumab, carboplatin, paclitaxel, and bevacizumab ● ●
Atezolizumab, carboplatin, and albumin-bound paclitaxel ● ●
Sometimes useful
Nivolumab with ipilimumab ● ●
Pembrolizumab ●
Guide 13
First-line treatment options by PD-L1 level
Preferred regimens Low PD-L1 High PD-L1
Pembrolizumab ●
Atezolizumab ●
Cemiplimab ●
Pembrolizumab, carboplatin, and paclitaxel ● ●
Pembrolizumab, carboplatin, and albumin-bound paclitaxel ● ●
Other regimens
Nivolumab, ipilimumab, carboplatin, and paclitaxel ● ●
Sometimes useful
Nivolumab with ipilimumab ● ●
Pembrolizumab ●

chemotherapy partly depends on the type of Maintenance treatment

cancer cell. Platinum-doublet chemotherapy If treatment results are good, you may shift
can cause health problems called side effects. to maintenance treatment, which includes
You must be healthy enough to get this some of your first-line treatments. This is
chemotherapy. called continuation maintenance. The goal
of maintenance treatment is to prolong the
Two checkpoint inhibitors, nivolumab and time until the cancer worsens. Options for
ipilimumab, are used together to treat lung maintenance treatment are listed in Guide 14.
cancer. They are given with platinum-doublet
chemotherapy. Within a few years on first-line treatment, lung
cancer starts to grow again in most people.
Atezolizumab with platinum-doublet Options after first-line treatment are listed in
chemotherapy is an option for non-squamous Chapter 5.
cell cancers. Bevacizumab is a part of one
atezolizumab regimen. It is a targeted therapy
called a VEGF antibody. It stops the growth
of blood vessels on tumors. Without blood,
cancer cells die.
Guide 14
Maintenance treatment options by PD-L1 level
Adenocarcinoma, large cell, and rare lung cancers Low PD-L1 High PD-L1
Pembrolizumab ● ●
Nivolumab and ipilimumab ● ●
Atezolizumab ● ●
Pembrolizumab and pemetrexed ● ●
Atezolizumab and bevacizumab ● ●
Cemiplimab ●
Pembrolizumab ● ●
Nivolumab and ipilimumab ● ●
Atezolizumab ●
Cemiplimab ●

4 Treatment by PD-L1 level Side effects
“
Side effects
Immunotherapy can cause your immune
cells to attack healthy cells in your body. This
results in health problems called side effects. Learning to manage side effects is
Immune-related side effects range from mild to well worth the effort!
life-threatening. They can occur during or after
treatment. Some side effects may worsen over
the course of treatment, with each treatment – Jon
dose. Most side effects can be managed if Lung cancer survivor
found and treated early.
NCCN has a two-part book series on

immunotherapy side effects. One book
focuses on side effects of immune checkpoint
inhibitors. It includes care options for many
side effects, such as:
Rash, itching, or blisters

Fatigue
Diarrhea
Low or high hormone levels
Lung inflammation
Joint and muscle pain
Heart inflammation
Dry eyes
Read about managing side effects in NCCN

Guidelines for Patients: Immunotherapy
Side Effects, Immune Checkpoint Inhibitors,
available at NCCN.org/patientguidelines.

4 Treatment by PD-L1 level Review
Review
The body’s defense against disease is
called the immune system. T cells are part
of this system. They kill cancer cells.
Immune checkpoints keep immune
responses in check. PD-1 and CTLA-4
are two types of immune checkpoints on
T cells.
In people with lung cancer, PD-1 and Let us know what
CTLA-4 are often activated and stop
T cells from killing cancer cells. you think!
Immune checkpoint inhibitors are a type of
Please take a moment to
immunotherapy. They prevent PD-1 and
CTLA-4 from being activated. complete an online survey
about the NCCN Guidelines
Immunotherapy options for lung cancer for Patients.
are based on the level of PD-L1. PD-L1 is
a protein on lung cancer cells that turns on
PD-1. When PD-1 is activated, T cells do NCCN.org/patients/response
not kill cancer cells.
When PD-L1 is high, immunotherapy
by itself can be used for treatment.
Immunotherapy combined with
chemotherapy is also standard treatment
for low and high PD-L1.
If treatment results are good, you may
stay on some of them to increase the time
until the cancer worsens. This is called
maintenance treatment.
Immunotherapy can cause your immune
cells to attack healthy cells in the body.
The immune-related health problems
range from mild to life-threatening. Most of
these health problems can be managed if
found and treated early.

5
Treatment by cell type
38 Cell type
39 Performance status
40 Systemic therapy
44 Clinical trials
45 Review

5 Treatment by cell type Cell type
Lung cancer differs between people There are 3 main types of lung cancer. They
based on the type of cell affected. are named after the normal cell from which the
Read this chapter to learn the best cancer formed:
treatment options based on cell type.
Treatment can be further improved Lung adenocarcinoma
with clinical trials. Large cell carcinoma
Squamous cell carcinoma
Cell type
Rare types of lung cancer are sometimes
described as “not otherwise specified (NOS).”
Most lung cancers do not have a known
biomarker for which there is treatment. When
there is no biomarker, treatment is based on
other factors, such as:
Type of cancer cell

Performance status
Health conditions and medications
Types of non-small
cell lung cancer
There are 3 main

types of lung cancer.
Adenocarcinoma is the most
common type. It is a cancer
of mucus-making cells. Large
cell carcinoma starts in large
cells of the lung. Squamous
cell carcinoma starts in
squamous cells.
Credit: https://commons.wikimedia.org/wiki/
File:Mucinous_lung_adenocarcinoma_--_high_
mag.jpg
https://commons.wikimedia.org/wiki/File:Large_
cell_carcinoma_of_the_lung_.jpg
https://commons.wikimedia.org/wiki/File:Lung_
squamous_carcinoma_--_high_mag.jpg

5 Treatment by cell type Performance status
Performance status that is in many places and in hard-to-reach

places. It is given in cycles of treatment days
Performance status is your ability to do day- followed by days of rest. The cycles vary in
to-day activities. Disease can limit what you length depending on which drugs are used.
can do. Your doctors will use your performance
status to decide what treatments are options A performance score of 3 or 4 suggests that
for you. cancer drugs will be too harmful. NCCN
experts advise receiving supportive care if
The Eastern Cooperative Oncology Group the cancer does not have a driver mutation.
(ECOG) Performance Status is a common Treatment of driver mutations is discussed in
scoring system. It consists of five scores Chapter 3.
ranging from 0 to 4. Lower scores represent a
better ability to do self-care. See Guide 15 for Supportive care aims to improve your quality of
treatment based on performance scores. life. It is sometimes called palliative care. One
of its aims is to treat the symptoms caused
Performance scores of 0 to 2 mean that by the cancer. Talk with your doctor about
you are fairly healthy. NCCN experts advise supportive care to get the best care plan for
receiving systemic therapy. Systemic therapy you.
is a term for cancer drugs that travel in the
bloodstream to the cancer. It can treat cancer
Guide 15
Performance status and treatment
Score Abilities Treatment
0 You are fully active. Systemic therapy
You are able to do self-care activities but unable to

1 Systemic therapy
do hard physical work.
You are able to do self-care activities and spend

2 most of waking time out of bed. You are unable to do Systemic therapy
any work.
You are unable to do self-care activities and any Supportive care if there is
3
work. You spend most of waking time in bed. no driver mutation
Supportive care if there is

4 You are fully disabled.
no driver mutation

5 Treatment by cell type Systemic therapy
Systemic therapy treatment. Another option is gemcitabine with

either docetaxel or vinorelbine.
The classic treatment of widespread metastatic
lung cancer is chemotherapy. Chemotherapy Bevacizumab is a part of some systemic
is a term for drugs that kill rapidly dividing regimens. It is a targeted therapy called a
cells. Newer treatments are sometimes used VEGF antibody. It stops the growth of blood
with chemotherapy to improve control of the vessels on tumors. Without blood, cancer cells
cancer. Treatment options for lung cancer die.
without biomarkers are listed in Guide 16 and
Guide 17. Sometimes, regimens with 2 chemotherapy
drugs are not options. Instead, a single-agent
chemotherapy may be given. There are
First-line treatments
several drugs that may be used:
For performance scores of 0 or 1,
chemotherapy with immunotherapy is standard
Albumin-bound paclitaxel
treatment. The type of immunotherapy used
is called immune checkpoint inhibitors. Docetaxel
Checkpoint inhibitors are used to treat lung
Gemcitabine
cancer with PD-L1 as discussed in Chapter 4.
They also extend life when lung cancer does Paclitaxel
not have PD-L1. There are 4 inhibitors used to
Pemetrexed (only for non-squamous cell
treat lung cancer based on cell type:
types)
Pembrolizumab (Keytruda®)
Side effects
Nivolumab (Opdivo®)
All cancer treatments cause health problems
Atezolizumab (Tecentriq )®
called side effects. Side effects from
chemotherapy are caused by the death of
Ipilimumab (Yervoy®)
fast-growing normal cells. Immune checkpoint
inhibitors can cause your immune cells to
Platinum-doublet chemotherapy is used with
attack healthy cells in your body.
checkpoint inhibitors for treatment. It consists
of cisplatin or carboplatin—drugs made with
Ask your treatment team for a complete list
platinum—and another type of chemotherapy.
of side effects of your treatments. Also, tell
Choice of chemotherapy partly depends on the
your treatment team about any new or worse
type of cancer cell.
symptoms you get. There may be ways to help
you feel better. There are also ways to prevent
Some people are not able to receive immune
some side effects.
checkpoint inhibitors. Checkpoint inhibitors may
not be an option because of an autoimmune
Read about immune-related side effects in
disease, certain medicines, or higher
NCCN Guidelines for Patients: Immunotherapy
performance scores. In these cases, platinum-
Side Effects, Immune Checkpoint Inhibitors.
doublet chemotherapy is most often used for
Fatigue, pain, and other side effects are

Guide 16
First-line systemic therapy by performance status (PS)
Adenocarcinoma, large cell, and rare types of lung cancer
Chemotherapy with immunotherapy PS 0 or 1 PS 2
(Carboplatin or cisplatin), pemetrexed, and pembrolizumab (preferred) ●
Carboplatin, paclitaxel, bevacizumab, and atezolizumab ●
Carboplatin, albumin-bound paclitaxel, and atezolizumab ●
Nivolumab and ipilimumab ●
(Carboplatin or cisplatin), pemetrexed, nivolumab, and ipilimumab ●
Chemotherapy without immunotherapy
Carboplatin, paclitaxel, and bevacizumab ●
(Carboplatin or cisplatin), pemetrexed, and bevacizumab ●
Cisplatin and another chemotherapy ●
Carboplatin and another chemotherapy ● ●
Gemcitabine and (docetaxel or vinorelbine) ● ●
Single-agent chemotherapy ●
Guide 17
First-line systemic therapy by performance status (PS)
Chemotherapy with immunotherapy PS 0 or 1 PS 2
Carboplatin, paclitaxel, and pembrolizumab (preferred) ●
Carboplatin, albumin-bound paclitaxel, and pembrolizumab (preferred) ●
Nivolumab and ipilimumab ●
Carboplatin, paclitaxel, nivolumab, and ipilimumab ●
Chemotherapy without immunotherapy
Cisplatin and another chemotherapy ●
Carboplatin and another chemotherapy ● ●
Gemcitabine and (docetaxel or vinorelbine) ● ●
Single-agent chemotherapy ●

addressed in NCCN Guidelines for Patients: The goal of maintenance treatment is to

Survivorship Care for Cancer-Related Late and increase the time until the cancer worsens.
Long-Term Effects. Both patient guides are You may stay on maintenance treatment for
available at NCCN.org/patientguidelines. 2 years if your first-line treatment included
immunotherapy. If immunotherapy was part of
second-line treatment, stay on maintenance
treatment until the cancer worsens.
Options after first-line treatment

In time, lung cancer often starts to grow again
after first-line treatment. Preferred treatments
include immune checkpoint inhibitors if not
received before. If the cancer worsened while
taking a checkpoint inhibitor, switching to
another checkpoint inhibitor is not advised.
Options after first-line treatment are listed in
Guide 19.
Other options include docetaxel with

Monitoring and maintenance
ramucirumab. Ramucirumab is a targeted
Systemic therapy is given in cyles of treatment
therapy called a VEGF antibody. Single-agent
days followed by days of rest. After 2 cycles,
chemotherapy is another option.
your doctor will assess the results. The extent
of the cancer can be seen on computed
Your doctor will monitor treatment results.
tomography (CT) scans. Contrast may be
You will get a CT scan every 6 to 12 weeks.
used. CT will be repeated after another 2 to 4
Contrast may be used.
cycles. In general, systemic therapy is given
for 4 cycles. If treatment isn’t making you too
sick, a total of 6 cycles may be completed.
If results are good at the end of treatment, you

may stay on at least one of the medicines. This
is called continuation maintenance. Another
option is changing to a medicine that you didn’t
take as a first-line treatment. This is called
switch maintenance. Options for maintenance
treatment are listed in Guide 18.

Guide 18
Maintenance treatment by lung cell type
Continuation maintenance
• Bevacizumab
• Pemetrexed
• Bevacizumab and pemetrexed
• Pembrolizumab and pemetrexed
Adenocarcinoma, large cell, and
• Atezolizumab and bevacizumab
rare types of lung cancer
• Atezolizumab
• Nivolumab and ipilimumab
• Gemcitabine
Switch maintenance
• Docetaxel
Continuation maintenance
• Nivolumab and ipilimumab
• Gemcitabine
• Pembrolizumab
Switch maintenance
• Pemetrexed
Guide 19
Options after you’ve had chemotherapy with or without immunotherapy
• Nivolumab
Preferred options • Pembrolizumab
• Atezolizumab
• Docetaxel
• Gemcitabine
Other options
• Ramucirumab and docetaxel
• Pemetrexed (non-squamous only)

5 Treatment by cell type Clinical trials
Clinical trials Who can enroll?

Every clinical trial has rules for joining, called
Despite advances in treatment, more research eligibility criteria. The rules may be about age,
is needed. There still is no cure for metastatic cancer type and stage, treatment history, or
lung cancer. Improving treatment is made general health. These requirements ensure
possible with clinical trials. that participants are alike in specific ways
and that the trial is as safe as possible for the
A clinical trial is a type of medical research participants.
study. After being developed and tested in
a laboratory, potential new ways of fighting
Informed consent
cancer need to be studied in people. If found
Clinical trials are managed by a group of
to be safe and effective in a clinical trial, a
experts called a research team. The research
drug, device, or treatment approach may
team will review the study with you in detail,
be approved by the U.S. Food and Drug
including its purpose and the risks and
Administration (FDA).
benefits of joining. All of this information is also
provided in an informed consent form. Read
Everyone with cancer should carefully consider
the form carefully and ask questions before
all of the treatment options available for their
signing it. Take time to discuss with family,
cancer type, including standard treatments and
friends, or others you trust. Keep in mind that
clinical trials. Talk to your doctor about whether
you can leave and seek treatment outside of
a clinical trial may make sense for you.
the clinical trial at any time.
Phases
Start the conversation
Most cancer clinical trials focus on treatment.
Don’t wait for your doctor to bring up clinical
Treatment trials are done in phases.
trials. Start the conversation and learn about
all of your treatment options. If you find a study
Phase I trials study the dose and safety
that you may be eligible for, ask your treatment
of an investigational drug or treatment
team if you meet the requirements. Try not to
approach.
be discouraged if you cannot join. New clinical
Phase II trials study how well the drug or trials are always becoming available.
approach works against a specific type of
cancer.
Frequently asked questions
Phase III trials test the drug or approach There are many myths and misconceptions
against a standard treatment. If the surrounding clinical trials. The possible
results are good, it may be approved by benefits and risks are not well understood by
the FDA. many with cancer.
Phase IV trials study the long-term
What if I get the placebo?
safety and benefit of an FDA-approved
A placebo is an inactive version of a real
treatment.
medicine. Placebos are almost never used
alone in cancer clinical trials. All participants

5 Treatment by cell type Review
receive cancer treatment. You may receive a Review

commonly used treatment, the investigational
drug(s), or both. Treatment for lung cancer without
biomarkers is partly based on the cell
Do I have to pay to be in a clinical trial? type.
Rarely. It depends on the study, your health
Performance status is your ability to do
insurance, and the state in which you live. Your
day-to-day activities. Doctors use this
treatment team and the research team can
status to decide which treatments are
help determine if you are responsible for any
safe options.
costs.
Systemic therapy consists of cancer
drugs. It is recommended for a
performance score of 0 through 2.
Supportive care is recommended for
scores 3 and 4.
Chemotherapy with immunotherapy
is standard treatment for fairly healthy
people. Other options are chemotherapy
Finding a clinical trial by itself or chemotherapy with
bevacizumab. The cancer drugs selected
for treatment are based on the cell type.
In the United States Learn about the side effects of your
NCCN Cancer Centers treatments. Let your treatment team know
NCCN.org/cancercenters about any new or worsening symptoms.
Your doctor will monitor the results of
The National Cancer Institute (NCI)
treatment. You may receive between 4
cancer.gov/about-cancer/treatment/clinical-trials/
and 6 cycles of treatment.
search
Maintenance treatment slows down the
Worldwide growth of the cancer. It consists of one or
more drugs from your first treatment.
The U.S. National Library of Medicine (NLM)
clinicaltrials.gov/ The next treatment options for lung
cancer are immunotherapy if not received
Need help finding a clinical trial? before, chemotherapy with ramucirumab,
and single-agent chemotherapy.
NCI’s Cancer Information Service (CIS)
1.800.4.CANCER (1.800.422.6237) Clinical trials are a type of research.
cancer.gov/contact New ways of fighting cancer are studied
among people in clinical trials. A clinical
trial may be an option in addition to
standard treatment.

6
Making treatment decisions
47 It’s your choice
47 Questions to ask your doctors
52 Resources

6 Making treatment decisions It’s your choice
It’s important to be comfortable with when considering options and making

the cancer treatment you choose. This treatment decisions.
choice starts with having an open and
honest conversation with your doctors. Second opinion
It is normal to want to start treatment as soon
as possible. While cancer can’t be ignored,
It’s your choice there is time to have another doctor review
your test results and suggest a treatment plan.
This is called getting a second opinion, and it’s
In shared decision-making, you and your
a normal part of cancer care. Even doctors get
doctors share information, discuss the options,
second opinions!
and agree on a treatment plan. It starts with an
open and honest conversation between you
Things you can do to prepare:
and your doctor.
Check with your insurance company
Treatment decisions are very personal. What
about its rules on second opinions. There
is important to you may not be important to
may be out-of-pocket costs to see doctors
someone else. Some things that may play a
who are not part of your insurance plan.
role in your decision-making:
Make plans to have copies of all your
What you want and how that might differ records sent to the doctor you will see for
from what others want your second opinion.
Your religious and spiritual beliefs
Support groups
Your feelings about certain treatments like
Many people diagnosed with cancer find
surgery or chemotherapy
support groups to be helpful. Support groups
Your feelings about pain or side effects often include people at different stages
such as nausea and vomiting of treatment. Some people may be newly
diagnosed, while others may be finished with
Cost of treatment, travel to treatment
treatment. If your hospital or community doesn’t
centers, and time away from work
have support groups for people with cancer,
Quality of life and length of life check out the websites listed on page 52.
How active you are and the activities that
are important to you
Questions to ask your doctors
Think about what you want from treatment.
Possible questions to ask your doctors are
Discuss openly the risks and benefits of
listed on the following pages. Feel free to use
specific treatments and procedures. Weigh
these questions or come up with your own. Be
options and share concerns with your doctor.
clear about your goals for treatment and find
If you take the time to build a relationship with
out what to expect from treatment.
your doctor, it will help you feel supported

6 Making treatment decisions Questions to ask your doctors
Questions to ask about testing and staging

1. What tests will I have? Is biomarker testing needed?
2. Do I need a biopsy? What kind of biopsy do I need? Will enough tissue be removed for
biomarker testing? What are the risks?
3. How do I prepare for testing?
4. What if I am pregnant?
5. Where do I go to get tested? How long will the tests take and will any test hurt?
6. Should I bring someone with me? Should I bring a list of my medications?
7. How soon will I know the results and who will explain them to me?
8. Would you give me a copy of the pathology report and other test results?
9. What type of lung cancer do I have? What is the stage? Has the cancer spread far?
10. Can this cancer be cured? If not, how well can treatment stop the cancer from growing?
11. Who will talk with me about the next steps? When?

Questions to ask about treatment options

1. What are my treatment options? Are you suggesting options other than what NCCN
recommends? If yes, why?
2. Do your suggested options include clinical trials? Please explain why.
3. What will happen if I do nothing?
4. How do my age, overall health, and other factors affect my options? What if I am
pregnant or planning to get pregnant?
5. Does any option offer a cure or long-term cancer control? Are my chances any better for
one option than another? Less time-consuming? Less expensive?
6. How do you know if treatment is working? How will I know if treatment is working?
7. What are my options if treatment stops working?
8. What are the possible complications? What are the short- and long-term side effects of
treatment?
9. What can be done to prevent or relieve the side effects of treatment?
10. What supportive care services are available to me during and after treatment?
11. Can I stop treatment at any time? What will happen if I stop treatment?

Questions to ask about clinical trials

1. Are there clinical trials for my type of cancer?
2. What are the treatments used in the clinical trial?
3. What does the treatment do?
4. Has the treatment been used before? Has it been used for other types of cancer?
5. What are the risks and benefits of this treatment?
6. What side effects should I expect? How will the side effects be controlled?
7. How long will I be in the clinical trial?
8. Will I be able to get other treatment if this doesn’t work?
9. How will you know the treatment is working?
10. Will the clinical trial cost me anything? If so, how much?

Questions to ask about getting treated

1. Will I have to go to the hospital or elsewhere? How often? How long is each visit?
2. What do I need to think about if I will travel for treatment?
3. Do I have a choice of when to begin treatment? Can I choose the days and times of
treatment?
4. How do I prepare for treatment? Do I have to stop taking any of my medicines? Are
there foods I will have to avoid?
5. Should I bring someone with me when I get treated?
6. Will the treatment hurt?
7. What should I do if a side effect gets bad when my cancer center is closed?
8. How much will the treatment cost me? What does my insurance cover?
9. Will I miss work or school? Will I be able to drive?
10. Is home care after treatment needed? If yes, what type?
11. How soon will I be able to manage my own health?
12. When will I be able to return to my normal activities?

6 Making treatment decisions Resources
Resources National Coalition for Cancer

Survivorship
canceradvocacy.org/toolbox
American Cancer Society
cancer.org/cancer/lung-cancer.html
NCCN Patient Resources
NCCN.org/patients
American Lung Association
lung.org
American Lung Cancer Screening

Initiative
alcsi.org
Caring Ambassadors Program, Inc.

lungcancercap.org
share with us.
Free ME from Lung Cancer
freeMEfromLungCancer.org
GO2 Foundation for Lung Cancer

go2foundation.org Take our survey
And help make the
Lung Cancer Alliance NCCN Guidelines for Patients
lungcanceralliance.org better for everyone!
NCCN.org/patients/comments
Lung Cancer Research Foundation
lcrf.org
LUNGevity Foundation
LUNGevity.org
National Cancer Institute (NCI)

cancer.gov/types/lung

Ü
Words to know
Words to know bronchioli

Small airways within the lungs.
bronchus
adenocarcinoma One of the two main airways that extends into
A cancer of cells that line organs and make the lungs.
fluids or hormones.
cancer stage
adrenal gland A rating of the outlook of a cancer based on its
A small organ on top of each kidney that growth and spread.
makes hormones.
carcinoma
AJCC A cancer of cells that line the inner or outer
American Joint Committee on Cancer surfaces of the body.
alveoli chemoradiation
The tiny sacs in the lungs where gases are A cancer treatment with both cell-killing drugs
transferred in and out of the blood. and high-energy rays.
anaplastic lymphoma kinase (ALK) chemistry profile
A type of protein on the edge of a cell that A lab test of the amount of 8 chemicals in a
sends signals for cell growth. sample of blood. Also called metabolic panel.
biomarker chemotherapy
Any molecule in your body that can be Cancer drugs that stop the cell life cycle so
measured to assess your health. cells don’t increase in number.
biomarker testing clinical stage
Tests of any molecule in your body that can be The rating of the extent of cancer before
measured to assess your health. Also called treatment is started.
molecular testing.
clinical trial
biopsy A type of research that assesses how well
A procedure that removes fluid or tissue health tests or treatments work in people.
samples to be tested for a disease.
complete blood count (CBC)
board certified A lab test that measures the parts of the blood.
A status for doctors who finished training in a
computed tomography (CT)
specialized field of medicine.
A test that uses x-rays from many angles to
body plethysmograph make a picture of the insides of the body.
A test of how much air is in your lungs after
continuation maintenance
inhaling or exhaling.
A treatment phase using one or more first-line
bronchi drugs to prolong good treatment results.
The two airways extending from the windpipe
contrast
into the lungs.
A dye put into your body to make clearer
pictures during imaging.

Words to know
core needle biopsy lymph node

A procedure that removes tissue samples with A small, bean-shaped, disease-fighting
a hollow needle. Also called core biopsy. structure.
diagnosis magnetic resonance imaging (MRI)
An identification of an illness based on tests. A test that uses radio waves and powerful
magnets to make pictures of the insides of the
DNA
body.
deoxyribonucleic acid
maintenance treatment
ECOG
A treatment phase that is given to prolong
Eastern Cooperative Oncology Group
good treatment results.
endobronchial ultrasound–guided
medical history
transbronchial needle aspiration (EBUS-
A report of all your health events and
TBNA)
medications.
A procedure that removes lung tissue with a
needle on an imaging device guided down the metastasis
windpipe. The spread of cancer from the first tumor to a
new site.
epidermal growth factor receptor (EGFR)
A protein on the edge of a cell that sends mutation
signals to the cell to grow. Abnormal changes in coded instructions within
cells (genes).
FDG
fluorodeoxyglucose NCCN
National Comprehensive Cancer Network
gas diffusion
A test that uses harmless gas to measure how non-small cell lung cancer (NSCLC)
much you can breathe out. A cancer that starts in lung cells that are not
small.
gene
Coded instructions in cells for making new NOS
cells and controlling how cells behave. Not otherwise specified
gene rearrangement pathologic stage
A coded instruction within a cell that is made A rating of the extent of cancer based on tests
from parts of other coded instructions. given after treatment.
immunotherapy pathologist
A treatment with drugs that help the body find A doctor who’s an expert in testing cells and
and destroy cancer cells. tissue to find disease.
large-cell lung carcinoma performance status
A cancer of lung cells that lack features to A rating of one’s ability to do daily activities.
classify as another type of lung cancer.
pericardiocentesis
lobe A procedure that removes fluid from around
A clearly seen division in an organ. the heart with a needle.

Words to know
physical exam side effect

A review of the body by a health expert for An unhealthy or unpleasant physical or
signs of disease. emotional response to treatment.
platinum-doublet chemotherapy small cell lung cancer (SCLC)
A treatment with two cell-killing drugs, one of A cancer of small, round lung cells.
which contains the chemical platinum.
spirometry
positron emission tomography (PET) A test that uses a tube to measure how fast
A test that uses radioactive material to see the you breathe.
shape and function of body parts.
squamous cell carcinoma
positron emission tomography/computed A type of cancer of thin and flat cells that line
tomography (PET/CT) the surface of organs.
A test that uses two picture-making methods to
stereotactic radiosurgery (SRS)
show the shape and function of tissue.
Treatment of a brain tumor with high-dose
prognosis radiation within one or a few sessions.
The likely course and outcome of a disease
supportive care
based on tests.
Health care that includes symptom relief but
pulmonary function tests not cancer treatment. Also sometimes called
A set of breathing tests to test the strength of palliative care.
the lungs.
surgery
radiation oncologist An operation to remove or repair a part of the
A doctor who’s an expert in treating cancer body.
with radiation.
switch maintenance
radiation therapy A treatment phase with a new drug that is
A treatment that uses intense energy to kill given to prolong good treatment results.
cancer cells.
targeted therapy
respiratory system A drug treatment that impedes the growth
The group of organs that transfers gases in process specific to cancer cells.
and out of the body.
thoracic radiologist
ROS1 A doctor who’s an expert in reading imaging
A type of protein on the edge of a cell that tests of the chest.
sends signals for cell growth.
thoracoscopy
stereotactic ablative radiotherapy (SABR) A procedure to do work in the chest with a
Treatment with high-dose radiation within one device passed through a small cut in the skin.
or a few sessions. Also called stereotactic Also called VATS.
body radiation therapy (SBRT).
trachea
The airway between the throat and airway into
the lungs. Also called the windpipe.

Words to know
transthoracic needle aspiration (TTNA)

A procedure that removes tissue samples with
a thin needle guided through the ribs.
ultrasound
A test that uses sound waves to take pictures of
the inside of the body.
vascular endothelial growth factor (VEGF)
A molecule that triggers the growth of blood
vessels.

NCCN Contributors
NCCN Contributors
This patient guide is based on the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung
Cancer, Version 4.2021. It was adapted, reviewed, and published with help from the following people:
Dorothy A. Shead, MS Laura J. Hanisch, PsyD John Murphy

Senior Director Medical Writer/Patient Information Specialist Medical Writer
Patient Information Operations
Stephanie Helbling, MPH, CHES ®
Erin Vidic, MA
Rachael Clarke Medical Writer Medical Writer
Senior Medical Copyeditor
Susan Kidney Kim Williams
Tanya Fischer, MEd, MSLIS Graphic Design Specialist Creative Services Manager
Medical Writer
The NCCN Guidelines® for Non-Small Cell Lung Cancer, Version 4.2021 were developed by the following NCCN Panel Members:
David S. Ettinger, MD/Chair Matthew A. Gubens, MD, MS Jose M. Pacheco, MD
The Sidney Kimmel Comprehensive UCSF Helen Diller Family University of Colorado Cancer Center
Cancer Center at Johns Hopkins Comprehensive Cancer Center
*Sandip P. Patel, MD
Douglas E. Wood, MD/Vice Chair Aparna Hegde, MD UC San Diego Moores Cancer Center
Fred Hutchinson Cancer Research Center/ O’Neal Comprehensive
Seattle Cancer Care Alliance Cancer Center at UAB Gregory J. Riely, MD, PhD
Memorial Sloan Kettering Cancer Center
Dara L. Aisner, MD, PhD Mark Hennon, MD
University of Colorado Cancer Center Roswell Park Comprehensive Cancer Center Steven E. Schild, MD
Mayo Clinic Cancer Center
Wallace Akerley, MD Rudy P. Lackner, MD
Huntsman Cancer Institute Fred & Pamela Buffett Cancer Center *Theresa A. Shapiro, MD, PhD
at the University of Utah The Sidney Kimmel Comprehensive
Michael Lanuti, MD Cancer Center at Johns Hopkins
Jessica R. Bauman, MD Massachusetts General Hospital
Fox Chase Cancer Center Cancer Center Aditi P. Singh, MD
Abramson Cancer Center at the
Ankit Bharat, MD Ticiana A. Leal, MD University of Pennsylvania
Robert H. Lurie Comprehensive Cancer University of Wisconsin
Center of Northwestern University Carbone Cancer Center James Stevenson, MD
Case Comprehensive Cancer Center/
Debora S. Bruno, MD, MS Jules Lin, MD University Hospitals Seidman Cancer
Case Comprehensive Cancer Center/ University of Michigan Rogel Cancer Center Center and Cleveland Clinic Taussig
University Hospitals Seidman Cancer Cancer Institute
Center and Cleveland Clinic Taussig Billy W. Loo, Jr., MD, PhD
Cancer Institute Stanford Cancer Institute Alda Tam, MD
The University of Texas
Joe Y. Chang, MD, PhD Christine M. Lovly, MD, PhD MD Anderson Cancer Center
The University of Texas Vanderbilt-Ingram Cancer Center
MD Anderson Cancer Center Tawee Tanvetyanon, MD, MPH
Renato G. Martins, MD, MPH Moffitt Cancer Center
Lucian R. Chirieac, MD Fred Hutchinson Cancer Research Center/
Dana-Farber/Brigham and Women’s Seattle Cancer Care Alliance Jane Yanagawa, MD
Cancer Center UCLA Jonsson
Erminia Massarelli, MD Comprehensive Cancer Center
Thomas A. D’Amico, MD City of Hope National Medical Center
Duke Cancer Institute Stephen C. Yang, MD
Daniel Morgensztern, MD The Sidney Kimmel Comprehensive
Thomas J. Dilling, MD, MS Siteman Cancer Center at Barnes- Cancer Center at Johns Hopkins
Moffitt Cancer Center Jewish Hospital and Washington
University School of Medicine
Jonathan Dowell, MD
UT Southwestern Simmons Thomas Ng, MD NCCN Staff
Comprehensive Cancer Center The University of Tennessee
Health Science Center Kristina Gregory, RN, MSN, OCN
Scott Gettinger, MD Vice President, Clinical Information Programs
Yale Cancer Center/Smilow Cancer Hospital *Gregory A. Otterson, MD
The Ohio State University Comprehensive
Travis E. Grotz, MD Cancer Center - James Cancer Hospital Miranda Hughes, PhD
Mayo Clinic Cancer Center and Solove Research Institute Oncology Scientist,/Seniior Medical Writer
* Reviewed this patient guide. For disclosures, visit NCCN.org/about/disclosure.aspx.

NCCN Cancer Centers
NCCN Cancer Centers

Abramson Cancer Center The Sidney Kimmel Comprehensive Stanford Cancer Institute
at the University of Pennsylvania Cancer Center at Johns Hopkins Stanford, California
Philadelphia, Pennsylvania Baltimore, Maryland 877.668.7535 • cancer.stanford.edu
800.789.7366 • pennmedicine.org/cancer 410.955.8964
www.hopkinskimmelcancercenter.org UC Davis
Fred & Pamela Buffett Cancer Center Comprehensive Cancer Center
Omaha, Nebraska Robert H. Lurie Comprehensive Sacramento, California
402.559.5600 • unmc.edu/cancercenter Cancer Center of Northwestern 916.734.5959 | 800.770.9261
University health.ucdavis.edu/cancer
Case Comprehensive Cancer Center/ Chicago, Illinois
University Hospitals Seidman Cancer 866.587.4322 • cancer.northwestern.edu UC San Diego Moores Cancer Center
Center and Cleveland Clinic Taussig La Jolla, California
Cancer Institute Mayo Clinic Cancer Center 858.822.6100 • cancer.ucsd.edu
Cleveland, Ohio Phoenix/Scottsdale, Arizona
800.641.2422 • UH Seidman Cancer Center Jacksonville, Florida UCLA Jonsson
uhhospitals.org/services/cancer-services Rochester, Minnesota Comprehensive Cancer Center
866.223.8100 • CC Taussig Cancer Institute 480.301.8000 • Arizona Los Angeles, California
my.clevelandclinic.org/departments/cancer 904.953.0853 • Florida 310.825.5268 • cancer.ucla.edu
216.844.8797 • Case CCC 507.538.3270 • Minnesota
case.edu/cancer mayoclinic.org/cancercenter UCSF Helen Diller Family
Comprehensive Cancer Center
City of Hope National Medical Center Memorial Sloan Kettering San Francisco, California
Los Angeles, California Cancer Center 800.689.8273 • cancer.ucsf.edu
800.826.4673 • cityofhope.org New York, New York
800.525.2225 • mskcc.org University of Colorado Cancer Center
Dana-Farber/Brigham and Aurora, Colorado
Women’s Cancer Center | Moffitt Cancer Center 720.848.0300 • coloradocancercenter.org
Massachusetts General Hospital Tampa, Florida
Cancer Center 888.663.3488 • moffitt.org University of Michigan
Boston, Massachusetts Rogel Cancer Center
617.732.5500 The Ohio State University Ann Arbor, Michigan
youhaveus.org Comprehensive Cancer Center - 800.865.1125 • rogelcancercenter.org
617.726.5130 James Cancer Hospital and
massgeneral.org/cancer-center Solove Research Institute The University of Texas
Columbus, Ohio MD Anderson Cancer Center
Duke Cancer Institute 800.293.5066 • cancer.osu.edu Houston, Texas
Durham, North Carolina 844.269.5922 • mdanderson.org
888.275.3853 • dukecancerinstitute.org O’Neal Comprehensive
Cancer Center at UAB University of Wisconsin
Fox Chase Cancer Center Birmingham, Alabama Carbone Cancer Center
Philadelphia, Pennsylvania 800.822.0933 • uab.edu/onealcancercenter Madison, Wisconsin
888.369.2427 • foxchase.org 608.265.1700 • uwhealth.org/cancer
Roswell Park Comprehensive
Huntsman Cancer Institute Cancer Center UT Southwestern Simmons
at the University of Utah Buffalo, New York Comprehensive Cancer Center
Salt Lake City, Utah 877.275.7724 • roswellpark.org Dallas, Texas
800.824.2073 214.648.3111 • utsouthwestern.edu/simmons
huntsmancancer.org Siteman Cancer Center at Barnes-
Jewish Hospital and Washington Vanderbilt-Ingram Cancer Center
Fred Hutchinson Cancer University School of Medicine Nashville, Tennessee
Research Center/Seattle St. Louis, Missouri 877.936.8422 • vicc.org
Cancer Care Alliance 800.600.3606 • siteman.wustl.edu
Seattle, Washington Yale Cancer Center/
206.606.7222 • seattlecca.org St. Jude Children’s Research Hospital/ Smilow Cancer Hospital
206.667.5000 • fredhutch.org
The University of Tennessee New Haven, Connecticut
Health Science Center 855.4.SMILOW • yalecancercenter.org
Memphis, Tennessee
866.278.5833 • stjude.org
901.448.5500 • uthsc.edu

Index
Index
ablation 24–25
blood test 12, 14
biomarker testing 12
biopsy 12, 15, 23
cancer stage 8
chemoradiation 10
chemotherapy 32–34, 40–42
clinical trial 44–45
driver mutation 21
imaging 12, 14–15, 42
immunotherapy 31–35, 40–42
lung function test 12, 18
medical history 12–13
NCCN Cancer Centers 59
NCCN Contributors 58
pathology report 16
performance status 12–13, 39
physical exam 12–13
radiation therapy 10, 24–25
second opinion 47
side effect 28, 35, 40
smoking 12–13
surgery 10, 24–25
supportive care 12, 18
targeted therapy 22–28

Ü
NCCN
GUIDELINES
FOR PATIENTS
®
Non-Small Cell
Lung Cancer
Metastatic
2021
NCCN Foundation gratefully acknowledges the following corporate supporters for helping to make available these NCCN Guidelines
for Patients: Astellas; AstraZeneca; Blueprint Medicines; Bristol Myers Squibb; Novartis Pharmaceutical Corporation; Pfizer Inc, and
Takeda Oncology. These NCCN Guidelines for Patients were also supported by a grant from Genentech, a member of the Roche Group.
NCCN independently adapts, updates and hosts the NCCN Guidelines for Patients. Our corporate supporters do not participate in the
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9 Based on treatment guidelines used by health care providers worldwide

9 Designed to help you discuss cancer treatment with your doctors

NCCN Guidelines for Patients®:

NCCN Guidelines for Patients® are developed by

NCCN Clinical Practice NCCN Guidelines

and supported by funding from NCCN Foundation®

NCCN Guidelines for Patients®:

With generous support from

To make a gift or learn more, please visit NCCNFoundation.org/donate

NCCN Guidelines for Patients®:

11 Tests for metastatic lung cancer

20 Treatment of driver mutations

30 Treatment by PD-L1 level

37 Treatment by cell type

46 Making treatment decisions

59 NCCN Cancer Centers

NCCN Guidelines for Patients®:

NCCN Guidelines for Patients®:

Airways of the lungs

Air moves through your body

NCCN Guidelines for Patients®:

Non-small cell lung cancer of cancer cells in mucus and no detection of a

For some people, cancer staging is done

NCCN Guidelines for Patients®:

Advanced Non-Small Cell Lung Cancer, Symptoms

 Trouble breathing, chronic cough, and

Lung cancer that has spread

NCCN Guidelines for Patients®:

NCCN Guidelines for Patients®:

NCCN Guidelines for Patients®:

• CBC with differential

• Diagnostic CT of the chest and upper abdomen

• Biopsy to remove tissue sample

NCCN Guidelines for Patients®:

Medical history Family history

NCCN Guidelines for Patients®:

Blood tests assesses if the chemicals in your blood are too

Pictures of the insides of

NCCN Guidelines for Patients®:

Diagnostic CT Biopsy vs. surgery

Your doctor will use imaging results to select

NCCN Guidelines for Patients®:

Cancer cell tests

NCCN Guidelines for Patients®:

Biomarker tests become cancer cells and support cancer

NCCN Guidelines for Patients®:

genetic testing, which assesses what a person Supportive care

Your palliative care doctor will work with your

NCCN Guidelines for Patients®:

Review  Pulmonary function tests are needed if

NCCN Guidelines for Patients®:

NCCN Guidelines for Patients®:

The nucleus is the control

NCCN Guidelines for Patients®:

Targeted therapy biomarker test results. If a driver mutation is

Kinases change the action of other proteins

NCCN Guidelines for Patients®:

First-line treatment After first-line treatment

Local treatment of limited tumors may be helpful for some people

Stay on first-line treatment if it has some benefit

Switch to a different targeted therapy

Trouble breathing, chronic cough, and

Review Pulmonary function tests are needed if

Rash, itching, or blisters

Type of cancer cell