Assessment of ECG Monitoring and

QTc Interval Prolongation in Patients

Receiving Ribociclib
Sarah Abu-Salih, PharmD | PGY1 Pharmacy Resident
Chelsea Gustafson, PharmD, BCOP | Clinical Pharmacy Specialist
Lindsey Koch, PharmD, BCOP| Clinical Pharmacy Specialist
Community Health Network | Indianapolis, IN
Disclosures
Chelsea Gustafson, PharmD, BCOP: Novartis
(Served on the Advisory Board Honorarium)
No other disclosures.
Abbreviations
• CDK4/6: Cyclin-Dependent Kinase 4 and 6
• CHN MDA: Community Health Network MD Anderson
• CTCAE: Common Terminology Criteria for Adverse Events
• ECG: Electrocardiogram
• ER/PR: Estrogen Receptor/Progesterone Receptor
• ET: Endocrine Therapy
• HER2: Human Epidermal Growth Factor Receptor 2
• Ms: Milliseconds
• NCCN: National Comprehensive Cancer Network
• QTc: Corrected QT
• QTcF: Corrected QT by Fridericia’s Formula
• SPSS: Statistical Package for the Social Sciences
Community Health Network
CHN MDA Centers
• Anderson
• East
• Kokomo
• North
• South

4
Background
 Breast Cancer
ET was
ER/PR+, HER2-
previously used
is currently the Resistance to
alone in
most ET develops in
metastatic or
diagnosed many patients
recurrent
subtype
disease

Hortobagyi GN, et al. N Engl J Med. 2022;386(10):942-950.

National Cancer institute. Tripathy D, et al. Clin Cancer Res. 2017;23(13):3251-3262.
 Ribociclib
CDK4/6 inhibitors
Overcomes ET- and ET are Among the CDK4/6
resistance by recommended first- inhibitors available,
targeting the line for ER/PR+, possesses unique
CDK4/6 pathway HER2- metastatic cardiotoxicity
breast cancer

Tripathy D, et al. Clin Cancer Res. 2017;23(13):3251-3262. Im S, et al. N Engl J Med. 2019;381:307-316.
National Comprehensive Cancer Network. 2024. Slamon DJ, et al. N Engl J Med. 2020;382:514-524.
 Ribociclib’s Cardiotoxicity
Recommended
QTc interval QTc interval
QTc intervals
prolongation monitoring:
changed by
to >500 ms
>60 ms in 6% • Prior to therapy
occurred in • 2 weeks after
of patients
1.4% patients initiation
• Start of cycle 2

Tripathy D, et al. Clin Cancer Res. 2017;23(13):3251-3262. Slamon DJ, et al. N Engl J Med. 2020;382:514-524.
Im S, et al. N Engl J Med. 2019;381:307-316. Novartis. 2023.
Need for Study
Adherence to ribociclib’s ECG monitoring requirements may be
difficult for providers and patients

Published research on adherence rates is lacking

Study results may guide quality improvement initiatives to

improve adherence

9
In patients starting ribociclib therapy, what is
the recommended frequency for ECG
monitoring to evaluate QTc interval changes?
A. 1 week after the initiation of therapy
B. Prior to starting and 2 weeks after initiation
C. Every month after initiation
D. Prior to therapy, 2 weeks after the initiation, at the start
of cycle 2, and as clinically indicated

10
When do the 2024 NCCN Breast Cancer
guidelines recommend the use of a CDK4/6
inhibitor?
A. First-line in combination with adjuvant chemotherapy for
stage II ER/PR-, HER2+ breast cancer
B. First-line in combination with ET for metastatic ER/PR+, HER2-
breast cancer
C. As adjuvant therapy for risk reduction in stage I ER/PR+, HER2-
breast cancer
D. First line for recurrent, unresectable ER/PR-, HER2+ breast
cancer

11
Methods & Objectives
Methods
Design
• A retrospective chart review of all patients initiated on ribociclib at CHN MDA Cancer
Centers between 03/13/2017 and 08/31/2023
Inclusion Criteria
• Adults ≥18 years of age
• Initial ribociclib prescription written by a CHN MDA provider
• Received ribociclib for ≥14 days
Exclusion Criteria
• Pregnancy
• Incarceration
• Adults >89 years of age when ribociclib was initiated
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Primary Outcome
-6 weeks to day 0
for day 0
Proportion of patients
who received ECG
monitoring for ribociclib ±1 week for day 14
at all recommended time
intervals
-1 week/+4 weeks
for cycle 2 start

14
Secondary Outcomes
Percentage of patients Proportion of patients
who received appropriate Mean increase in QTc with CTCAE v5.0 grade 2
ECG monitoring for each interval or higher QTc interval
recommended time point prolongation

Proportion of patients
Mean number of days to
who had a dose
first incidence of CTCAE
interruption/adjustment
v5.0 grade 2 or higher
of ribociclib based on QTc
QTc interval changes
interval changes

15
FDA Recommendations
If QTcF >480 ms:
• Interrupt ribociclib therapy
• Once QTcF prolongation resolves to <481 ms,
In this study, QT intervals were resume treatment at the next lower dose
corrected by Fridericia’s
formula (QTcF)
If QTcF >500 ms or changes by >60 ms from
baseline:
• Permanently stop ribociclib therapy if
correlated with Torsades de Pointes

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CTCAE v5.0 Grading
Grade Investigations
1 Average QTc 450-480 ms

2 Average QTc 481-500 ms

3 Average QTc ≥501 ms; >60 ms change from baseline

4 Torsade de Pointes

17
Results
Statistical Analysis

SPSS was utilized to perform

statistical analysis

19
Study Enrollment
82 patient charts were reviewed

24 patients were excluded due

to ribociclib being started by a
provider outside of CHN MDA
4 patients were excluded for not
continuing ribociclib for ≥2
weeks

54 patients were included

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Treatment Location
6% 6%

33%

35%

20%

Anderson East Kokomo North South

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Baseline Characteristics
Mean (SD)

Age (n=54) 65 (13.4)

Weight, kg (n=54) 78 (21.4)

Height, cm (n=54) 163 (8)

Baseline eGFR, mL/min (n=50) 77 (22.1)

22
Baseline Characteristics

Sex %
Female 94.4 (n=51)
Male 5.6 (n=3) Cancer Stage %
I-III 5.6 (n=3)
IV 94.4 (n=51)

23
Baseline Characteristics
Comorbidities %
Concurrent ET % Chronic Kidney
9.3 (n=5)
Letrozole 44.4 (n=24) Disease
History of
Fulvestrant 37 (n=20) Myocardial 1.9 (n=1)
Anastrozole 14.8 (n=8) Infarction
Exemestane 1.9 (n=1) Atrial Fibrillation 1.9 (n=1)
Tamoxifen 1.9 (n=1) Heart Failure N/A (n=0)
Liver Disease N/A (n=0)

24
Primary Outcome
Percentage of Patients with ECGs Obtained at All
Recommended Time Intervals

29.6%
(n=16)
70.4%
(n=38)

Yes No
25
Secondary Outcomes
Percentage of Patients Who Received Appropriate ECG Monitoring for
Each Recommended Time Point

83.3% (n=45)
Day 0
16.6% (n=9)

53.7% (n=29)
Day 14
46.3% (n=25)

51.9% (n=28)
Cycle 2
48.1% (n=26)

0 10 20 30 40 50 60 70 80 90

Yes No
26
Secondary Outcomes
Mean, days
Mean, ms (SD) %
(SD)

Patients with
Increase in QTc Days to ≥CTCAE
≥CTCAE v5.0
Interval after v5.0 Grade 2
Grade 2 QTc
Initiation of 17 (13.5) 3.7 QTc Interval 19 (9.2)
Interval
Ribociclib Prolongation
Prolongation
(n=39) (n=2)
(n=2)

27
Secondary Outcomes
%
Discontinuation of
Ribociclib Therapy due
to QTc Interval 2.6
Prolongation >480 ms
(n=1)

%
Dose Adjustment of
Ribociclib Therapy due
to QTc Interval 2.6
Prolongation >480 ms
(n=1)
28
Strengths
Duration of study Multi-site

Identified need to
Extensive access to optimize compliance
prescribing data to ECG monitoring
with ribociclib

29
Limitations
Small patient population

Retrospective design

Confounding variables

Descriptive nature of data

30
Conclusion
Of the total 54 patients included in this study,
16 patients had ECGs obtained at all
recommended time intervals.
An opportunity exists to improve adherence to
the ECG monitoring recommendations provided
by the FDA.

31
Future Considerations
What obstacles impede adherence to the FDA-
recommended ECG monitoring for patients and providers?

What initiatives can be implemented to improve compliance

to the FDA-recommended ECG monitoring?

Is ribociclib’s use limited by its ability to cause QTc interval

prolongation in larger patient populations or longer
durations of follow-up?

32
Acknowledgements
• Co-investigators:
• Chelsea Gustafson, PharmD, BCOP | Clinical Pharmacy Specialist
• Lindsey Koch, PharmD, BCOP| Clinical Pharmacy Specialist

• Research Mentor:
• Tina Keller, PharmD | Drug Information Pharmacist

• Statistician:
• Jaclyn Myers, PharmD, PhD | Informatics Pharmacist

33
References
• National Cancer Institute. Cancer Stat Facts: Female Breast Cancer Subtypes. https://seer.cancer.gov/statfacts/html/breast-subtypes.html
(accessed 2023 Aug 10).

• Hortobagyi GN, Stemmer SM, Burris HA, et al. Overall survival with ribociclib plus letrozole in advanced breast cancer. N Engl J Med.
2022;386(10):942-950.

• Tripathy D, Bardia A, Sellers WR. Ribociclib (LEE011): Mechanism of action and clinical impact of this selective cyclin-dependent kinase 4/6
inhibitor in various solid tumors. Clin Cancer Res. 2017;23(13):3251-3262.

• National Comprehensive Cancer Network. Breast Cancer (Version 2.2024). https://www.nccn.org/professionals/physician_gls/pdf/breast.pdf

(accessed 2024 Mar 19).

• Im S, Lu Y, Bardia A, et al. Overall survival with ribociclib plus endocrine therapy in breast cancer. N Engl J Med. 2019;381:307-316.

• Slamon DJ, Neven P, Chia S, et al. Overall survival with ribociclib plus fulvestrant in advanced breast cancer. N Engl J Med. 2020;382:514-524.

• Kisqali (ribociclib) [package insert]. East Hanover, NJ: Novartis; 2023.

34
Assessment of ECG Monitoring and
QTc Interval Prolongation in Patients
Receiving Ribociclib
Sarah Abu-Salih, PharmD | PGY1 Pharmacy Resident
Chelsea Gustafson, PharmD, BCOP | Clinical Pharmacy Specialist
Lindsey Koch, PharmD, BCOP| Clinical Pharmacy Specialist
Community Health Network | Indianapolis, IN