Printed by Isobel Webster on 10/21/2021 3:08:02 PM. For personal use only. Not approved for distribution.

Copyright © 2021 National Comprehensive Cancer Network, Inc., All Rights Reserved.
Chemotherapy Order Template BRS187b
Page 1 of 2
Breast Cancer
Pembrolizumab + PACLitaxel/CARBOplatin followed by Pembrolizumab +
Cyclophosphamide/[DOXOrubicin or EpiRUBicin] followed by Pembrolizumab
Pembrolizumab + Cyclophosphamide/[DOXOrubicin or EpiRUBicin](Neoadjuvant Course 2)

INDICATION: REFERENCES: NCCN SUPPORTIVE CARE:

HER2 negative and Hormone receptor negative: 1. NCCN Guidelines® for Breast Cancer 1. Emetic risk: Day 1 High
Neoadjuvant - High-risk V.7.2021. 2. Febrile Neutropenia Risk: Refer to Myeloid
2. Schmid P , et al. N Engl J Med. Growth Factor algorithms in the NCCN
2020;382(9):810-821.a Guidelines for Hematopoietic Growth Factors

CHEMOTHERAPY REGIMEN
Early and late-onset immune-related adverse events affecting multiple organ systems can occur in patients receiving immune checkpoint inhibitors.
Patients with neurologic or life-threatening autoimmune disorders as well as those receiving high levels of immunosuppression for their underlying
disease should be approached with caution when considering immunotherapy. All patients will require extensive resources including ongoing
intensive monitoring and supportive care. See Other Supportive Therapy, Monitoring and Hold Parameters, and Safety Parameters and Special
Instructions for recommendations. Refer to the Management of Immunotherapy-Related Toxicities guideline for more information.
21-day cycle for 4 cycles
Pembrolizumab 200 mg IV over 30 minutes on Day 1
followed by
Cyclophosphamide 600 mg/m² IV over 30 minutes on Day 1
Oral hydration is strongly encouraged with cyclophosphamide; poorly hydrated patients may need supplemental IV hydration. Patients
should attain combined oral and IV hydration of 2,000 – 3,000 mL/day on day of chemotherapy.
See Other Supportive Therapy for example of IV hydration.
DOXOrubicin 60 mg/m² IV push on Day 1
See Safety Parameters and Special Instructions for information on slow IV Push administration.
or
EpiRUBicin 90 mg/m² IV push on Day 1
See Safety Parameters and Special Instructions for information on slow IV Push administration.
This course is Pembrolizumab + Cyclophosphamide/[DOXOrubicin or EpiRUBicin] (Neoadjuvant Course 2) every 21 days for 4 cycles. This course is
initiated following completion of Pembrolizumab + PACLitaxel/CARBOplatin (Neoadjuvant Course 1). Pembrolizumab (Adjuvant) course is initiated
following completion of this course. Please see order templates BRS187a for the Pembrolizumab + PACLitaxel/CARBOplatin (Neoadjuvant Course 1)
and BRS187c for the Pembrolizumab (Adjuvant) course.
SUPPORTIVE CARE
Antiemetic Therapy
Scheduled prophylactic antiemetic therapy should be given for prevention of acute and delayed nausea and vomiting based on the emetic risk of
the chemotherapy regimen. This may include antiemetic therapy given on the days following chemotherapy. For more information on emetic
prophylaxis, refer to the NCCN Guidelines for Antiemesis and Appendix D to the NCCN Chemotherapy Order Templates.
PRN for breakthrough: All patients should be provided with at least one medication for breakthrough emesis. Please consult the NCCN
Guidelines for Antiemesis for appropriate antiemetic therapy.
Other Supportive Therapy
For pembrolizumab:
This agent may cause severe, life-threatening immune-mediated adverse reactions. These immune-mediated reactions may involve
one or more organ system; however, the most common severe immune-mediated reactions are pneumonitis, colitis, hepatitis,
myocarditis, endocrinopathies, exfoliative dermatologic conditions, renal failure and nephritis, and ocular toxicities. Please refer
to NCCN Guidelines for Management of Immunotherapy-Related Toxicities and specific drug package insert. While most of these
reactions occur during treatment, some occur weeks to months after discontinuation of therapy. In the setting of immune-mediated
reactions, this agent may be held, and for severe reactions, this agent should be permanently discontinued. High-dose systemic
corticosteroid therapy should be initiated for immune-mediated reactions according to specific recommendations in the drug package
insert.
This agent may cause severe life-threatening diarrhea. Episodes of diarrhea should be monitored prior to each dose and as clinically
indicated. Modification or discontinuation of therapy may be warranted. Review drug package insert for specific recommendations on
antidiarrheal medication and/or systemic corticosteroids. Patients may require IV hydration and electrolyte replacement.
This agent may cause severe, life-threatening endocrinopathies. Systemic corticosteroids and appropriate hormone replacement
therapy should be initiated in symptomatic patients.
This agent may cause new onset type 1 diabetes mellitus with ketoacidosis. Blood glucose should be monitored prior to each dose and
as clinically indicated. Modification or discontinuation of therapy may be warranted. Patients may require insulin replacement therapy
according to specific recommendations in the drug package insert.
For cyclophosphamide: Example of recommended hydration: Sodium chloride 0.9% infused IV at a rate of 1.5 – 3 mL/kg/hour for a total of
500 mL on day of chemotherapy.

Template continued on page 2

NCCN Chemotherapy Order Templates (NCCN Templates®) are peer-reviewed statements of the consensus of its authors derived from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®)
regarding their views of currently accepted approaches to treatment. An NCCN Template does not constitute an order. Any clinician seeking to treat a patient using the NCCN Templates® is expected to use
independent medical judgment in the context of individual clinical circumstances of a specific patient's care or treatment. NCCN disclaims all warranties, express or implied including, without limitation, the
implied warranties of merchantability and fitness for a particular purpose. NCCN does not warrant the accuracy, currency, or completeness of the NCCN Templates or make any representation regarding the
use or the results of the use of the NCCN Templates in treatment. In no event shall NCCN or its members be liable for any damages including, without limitation, incidental, indirect, special, punitive, or
consequential damages arising out of or in connection with the use of the NCCN Templates including, without limitation, loss of life, loss of data, loss of income or profit, losses sustained as a result of any
injury to any person, or loss or damage to property or claims of third parties.
National Comprehensive Cancer Network, Inc. © 2021. All rights reserved. 09/29/2021
 Printed by Isobel Webster on 10/21/2021 3:08:02 PM. For personal use only. Not approved for distribution. Copyright © 2021 National Comprehensive Cancer Network, Inc., All Rights Reserved.
Chemotherapy Order Template BRS187b
Page 2 of 2
Breast Cancer
Pembrolizumab + PACLitaxel/CARBOplatin followed by Pembrolizumab +
Cyclophosphamide/[DOXOrubicin or EpiRUBicin] followed by Pembrolizumab
Pembrolizumab + Cyclophosphamide/[DOXOrubicin or EpiRUBicin](Neoadjuvant Course 2)

MONITORING AND HOLD PARAMETERS

CBC with differential should be monitored as clinically indicated for potential dose modification.
For pembrolizumab:
Infusion reactions may occur with administration. Monitor for and treat infusion reactions (e.g. fever, chills, flushing, itching and/or
muscle pain) per institutional standard. Initiation and/or adjustment of premedications should be considered. Infusion rate changes may
be warranted. Refer to the "Infusion-Related Reactions" algorithm in the NCCN Guidelines for Management of Immunotherapy-Related
Toxicities for additional information and recommendations.
This agent may cause pneumonitis. Signs and symptoms of pneumonitis should be monitored prior to each dose for potential dose
modification or discontinuation.
This agent may cause colitis. Signs and symptoms should be monitored prior to each dose for potential dose modification or
discontinuation.
Monitor for signs and symptoms of hypophysitis, adrenal insufficiency, and hyper- or hypothyroidism. Thyroid function tests should be
monitored prior to initiation of therapy and as clinically indicated. Endocrine toxicities may develop during treatment or weeks to months
following completion of treatment.
Serum glucose should be monitored prior to each dose and as clinically indicated.
Renal function should be monitored prior to each dose for potential dose modification or discontinuation.
Liver function should be monitored prior to each dose for potential dose modification or discontinuation.
Dermatologic toxicity should be monitored prior to each dose for potential dose modification or discontinuation.
For cyclophosphamide: Renal function should be monitored as clinically indicated for potential dose modification or discontinuation.
For DOXOrubicin:
This agent is an anthracycline. Cumulative anthracycline dosage should be monitored.
Ejection fraction should be monitored prior to initiation of treatment and as clinically indicated.
Liver function should be monitored prior to each cycle and as clinically indicated for potential dose modification or discontinuation.
For epiRUBicin:
This agent is an anthracycline. Cumulative anthracycline dosage should be monitored.
Ejection fraction should be monitored prior to initiation of treatment and as clinically indicated.
Liver function should be monitored prior to each cycle for potential dose modification or discontinuation.
SAFETY PARAMETERS AND SPECIAL INSTRUCTIONS
For pembrolizumab: This agent should be administered through a low protein binding 0.2 – 5 micron in-line filter.
For cyclophosphamide: Secondary malignancies have been associated with this drug. Review drug package insert for additional information.
For DOXOrubicin:
This agent is a vesicant OR an irritant with vesicant properties.
This agent is administered IV push. The preferred IV push method for a vesicant is administration through the side port of a freely
flowing IV.
Central venous access is recommended for administration of this agent.
Secondary malignancies have been associated with this drug. Review drug package insert for additional information.
For epiRUBicin:
This agent is a vesicant OR an irritant with vesicant properties.
This agent is administered IV push. The preferred IV push method for a vesicant is administration through the side port of a freely
flowing IV.
Central venous access is recommended for administration of this agent.
Secondary malignancies have been associated with this drug. Review drug package insert for additional information.

NCCN Chemotherapy Order Templates (NCCN Templates®) are peer-reviewed statements of the consensus of its authors derived from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®)
regarding their views of currently accepted approaches to treatment. An NCCN Template does not constitute an order. Any clinician seeking to treat a patient using the NCCN Templates® is expected to use
independent medical judgment in the context of individual clinical circumstances of a specific patient's care or treatment. NCCN disclaims all warranties, express or implied including, without limitation, the
implied warranties of merchantability and fitness for a particular purpose. NCCN does not warrant the accuracy, currency, or completeness of the NCCN Templates or make any representation regarding the
use or the results of the use of the NCCN Templates in treatment. In no event shall NCCN or its members be liable for any damages including, without limitation, incidental, indirect, special, punitive, or
consequential damages arising out of or in connection with the use of the NCCN Templates including, without limitation, loss of life, loss of data, loss of income or profit, losses sustained as a result of any
injury to any person, or loss or damage to property or claims of third parties.
National Comprehensive Cancer Network, Inc. © 2021. All rights reserved. 09/29/2021