Verzenios ® ▼ (abemaciclib)

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What were the most frequent adverse events with Verzenios® ▼ (abemaciclib) in early breast cancer?

The most common treatment-emergent adverse events in the abemaciclib treatment arm at the AFU1 analysis of monarchE were diarrhea (83.5%), neutropenia (45.8%), and fatigue (40.6%).

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Abemaciclib: most frequent adverse events in early breast cancer (EBC)

Clinically Relevant Adverse Events in Abemaciclib-Treated Patients in monarchE

Information on the adverse events (AEs) that are considered clinically relevant to abemaciclib at the AFU1 analysis are summarized in Clinically Relevant AEs Observed in At Least 10% of Patients in Abemaciclib + ET Arm in monarchE at AFU1 Analysis . Data on the ET only arm are included for comparison.1

In monarchE, the most frequent clinically relevant AEs of any grade occurring in ≥10% patients in the abemaciclib arm were diarrhea, infections, neutropenia, fatigue, nausea, anemia, headache, vomiting, stomatitis, thrombocytopenia, decreased appetite, alopecia, increased alanine aminotransferase or aspartate aminotransferase, and rash.1

Grade ≥3 AEs occurred more frequently in patients treated with abemaciclib (49.7% vs 16.3%) and were predominantly laboratory cytopenias without clinical complications.1

Clinically Relevant AEs Observed in At Least 10% of Patients in Abemaciclib + ET Arm in monarchE at AFU1 Analysis 1

 

Abemaciclib + ET

(N=2791)

ET Alone

(N=2800)

Event Term, %

Any Grade

Grade 1

Grade 2

Grade 3

Any Grade

Grade 1

Grade 2

Grade 3

Patients with 1 AEa

98.4

5.9

42.7

49.7

88.8

22.6

49.9

16.3

Diarrhea

83.5

45.0

30.7

7.8b

8.6

6.6

1.9

0.2

Infectionsc

51.2

8.8

36.9

5.6

39.4

8.2

28.2

3.0d

Neutropenia

45.8

6.4

19.8

19.6

5.6

2.4

2.4

0.8

Fatigue

40.6

22.6

15.1

2.9

17.8

13.5

4.2

0.1

Nausea

29.5

22.3

6.7

0.5

9.0

7.1

1.9

0.1

Anemia

24.4

13.7

8.6

2.0

3.7

2.7

0.7

0.4

Headache

19.6

14.9

4.4

0.3

15.0

11.5

3.4

0.2

Vomiting

17.6

13.4

3.6

0.5

4.6

3.5

1.0

0.1

Stomatitise

13.8

11.1

2.6

0.1

5.4

4.8

0.6

0.0

Thrombocytopenia

13.4

9.9

2.2

1.3

1.9

1.4

0.3

0.1

Decreased appetite

11.8

8.7

2.5

0.6

2.4

1.9

0.5

0.1

Alopecia

11.2

10.1

1.1

NA

2.7

2.4

0.3

0.0

ALT increase

12.3

6.6

2.9

2.8

5.6

4.0

0.9

0.7

AST increase

11.8

7.9

2.1

1.9

4.9

3.7

0.7

0.5

Rash

11.2

8.6

2.2

0.4

4.5

3.7

0.8

0.0

Abbreviations: AE = adverse event; AFU1 = additional follow-up 1; ALT = alanine aminotransferase; AST = aspartate aminotransferase; CTCAE = Common Terminology Criteria for Adverse Events; ET = endocrine therapy; NCI = National Cancer Institute.

aThe severity of AEs were recorded by investigators and graded by the NCI-CTCAE v4.

bNo G4 events, one G5 event.

cInfection is a composite term that includes all reported preferred terms that are part of the infections and infestations system organ class.

dFour G5 events.

eStomatitis is a consolidated term that includes mouth ulceration, mucosal inflammation, oropharyngeal pain, and stomatitis.

Common Treatment-Emergent Adverse Events in monarchE

The most common treatment-emergent adverse events (TEAEs) in the abemaciclib treatment arm at the AFU1 analysis were diarrhea, neutropenia, and fatigue as seen in Most Common TEAEs in the Abemaciclib Arm or ET Alone Arm at the AFU1 Analysis of monarchE. The most common TEAEs in the ET alone arm were arthralgia, hot flush, and fatigue. Other TEAEs are listed in Most Common TEAEs in the Abemaciclib Arm or ET Alone Arm at the AFU1 Analysis of monarchE.2

Most Common TEAEs in the Abemaciclib Arm or ET Alone Arm at the AFU1 Analysis of monarchE2

 

Abemaciclib + ET
(N=2791)

ET Alone
(N=2800)

    TEAE, %

Any Grade

Grade 3

Grade 4

Any Grade

Grade 3

Grade 4

Diarrhea

83.5

7.8 

0a

8.6

0.2 

0 

Neutropenia 

45.8

18.9 

0.7 

5.6 

0.7 

0.1 

Fatigue  

40.6

2.9 

NAb 

17.8

0.1 

NAb

Leukopenia 

37.6

11.2

0.1 

6.6 

0.4 

NA b

Abdominal pain 

35.5

1.4 

NAb

9.8

0.3 

NAb  

Nausea 

29.5

0.5 

NA b 

9.0

0.1 

NAb

Arthralgia 

26.6

0.3

NAb

37.9

1.0

NAb

Anemia 

24.4

2.0

0.0

3.7 

0.3 

0.0

Headache

19.6

0.3

NAb 

15.0

0.2

NAb

Vomiting

17.6

0.5

0

4.6

0.1

0

Hot flush 

15.3

0.1 

NAb

23.0

0.4 

NA b

Lymphopenia

14.2

5.3

0.1

3.4

0.5

0

Cough

14.0

0.0

NA b

7.9

0

NA b

Thrombocytopenia

13.4

1.0

0.3

1.9

0.1

0.1

Lymphedema

12.4

0.2

NA b

8.9

0.0

NA b

Alanine aminotransferase increase

12.3

2.6

0.2

5.6

0.7

0

Urinary tract infection

12.0

0.6

0

7.5

0.2

0

Constipation

11.9

0.1

0

6.0

0.0

0

Aspartate aminotransferase increased

11.8

1.8

0.1

4.9

0.5

0

Decreased appetite

11.8

0.6

0

2.4

0.1

0

Alopecia

11.2

NAc 

NAc 

2.7

NAc

NAc

Rash

11.2

0.4

0

4.5

0

0

Blood creatinine increased

11.1

0.1

0

0.8

0

0

Dizziness

10.9

0.1

NAb 

6.7

0.0

NAb 

Upper respiratory tract infection

10.8

0.2

0

8.5

0

0

Pain in extremity

10.2

0.1

NAb 

11.6

0.1

NAb 

Back pain

10.1

0.4

NAb 

12.4

0.3

NAb 

Pyrexia

10.0

0.1

00

4.5

0

0

VTEd

   PE

2.5

1.0

1.1

0.9

0.2

0.1

0.6

0.1

0.3

0.1

0a

0a

ILDe

3.2

0.4

0b

1.3

0.0

0

Abbreviations: AFU1 = additional follow-up 1; CTCAE = Common Terminology Criteria for Adverse Events; ET = endocrine therapy; ILD = interstitial lung disease; MedDRA = Medical Dictionary for Regulatory Activities; NA = not applicable; PE = pulmonary embolism; SMQ =Standardised MedDRA Queries; TEAE = treatment-emergent adverse event; VTE = venous thromboembolism.

aOne Grade 5 event occurred.

bMax Grade 3 event (according to CTCAE v4).

cMax Grade 2 event (according to CTCAE v4).

dIdentified by selected terms in Embolic and thrombotic events SMQ.

eIdentified by Interstitial lung disease SMQ.

Adverse Events of Interest in monarchE

Adverse events of interest occurring in the abemaciclib + ET arm of monarchE are summarized below:

  • Diarrhea was mostly low grade (grade 1/2: 76%); grade 2/3 events were highest in the first month (20.5%), and most were short-lived (≤7 days) and did not recur.
  • Neutropenia was the most frequently reported grade ≥3 AE (19.6%), with a median time to onset of 1 month, and was not associated with severe infections.
  • Fatigue was predominantly grade 1 (22.6%).
  • Grade ≥3 increased transaminases was reported at 3.5% (median time to onset: 3 months) and was managed with a dose hold or reduction and mostly did not recur.
  • Increased serum creatinine was the most common laboratory abnormality reported with 99% of patients having a grade 1 or 2 event.
  • Most VTEs were grade ≥3 and primarily PE events (1.0%) leading to hospitalization in only 0.7% of those with a PE.
    • Increased VTE risk was observed with tamoxifen as the initial ET compared to aromatase inhibitors (4.3% vs 1.8%).
  • Most ILD events were grade 1 and primarily pneumonitis, with 0.4% experiencing grade ≥3 events and 1 fatal event.
  • Any grade alopecia occurred in 11.2% of the abemaciclib-treated patients.
  • The safety profile across the age subgroups was generally consistent with the overall safety profile.1,3

    Serious Adverse Events and Deaths in monarchE

    Serious adverse events occurred more frequently in patients treated with abemaciclib (15.2% vs 8.8%). There were 15 (0.5%) and 10 (0.4%) deaths due to AEs on study treatment or ≤30 days from discontinuation in the abemaciclib + ET arm and ET alone arm, respectively.1

    Conclusion

    Abemaciclib + ET demonstrated an acceptable safety profile in patients with high-risk EBC at the AFU1 analysis in monarchE (median follow-up, 27 months). Most AEs were reversible and manageable with comedications and/or dose modifications, consistent with the established safety profile of abemaciclib.1

    monarchE Trial

    monarchE is an open-label, randomized, phase 3 trial comparing adjuvant abemaciclib 150 mg twice daily plus endocrine therapy (ET) vs ET alone for a 2-year duration in 5637 patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-), node-positive, early breast cancer (EBC) at high risk of recurrence.

    At the end of the study treatment, patients entered physician-directed ET follow-up for 5-10 years, as clinically indicated. At the preplanned interim analysis in June 2020, this event-driven trial met its primary objective of superior invasive disease-free survival (IDFS) when abemaciclib was combined with ET compared to ET alone.4 The trial is active but not recruiting.5

    The safety data presented in this response are based on the most recent additional follow-up 1 (AFU1) analysis of monarchE (median follow-up, 27 months; data cutoff date: April 1, 2021). The median duration of abemaciclib treatment was 24 months, and the median exposure to ET was 24 months in both arms. Safety data from the AFU1 analysis are considered to be mature as 90% of patients were off study drug.1

    References

    1Rugo HS, O’Shaughnessy J, Boyle F, et al; monarchE Committee Members. Adjuvant abemaciclib combined with endocrine therapy for high-risk early breast cancer: safety and patient-reported outcomes from the monarchE study. Ann Oncol. 2022;33(6):616-627. https://doi.org/10.1016/j.annonc.2022.03.006

    2Harbeck N, Rastogi P, Martin M, et al; monarchE Committee Members. Adjuvant abemaciclib combined with endocrine therapy for high-risk early breast cancer: updated efficacy and Ki-67 analysis from the monarchE study. Ann Oncol. 2021;32(12):1571-1581. https://doi.org/10.1016/j.annonc.2021.09.015

    3Data on file, Eli Lilly and Company and/or one of its subsidiaries.

    4Johnston SRD, Harbeck N, Hegg R, et al; monarchE Committee Members and Investigators. Abemaciclib combined with endocrine therapy for the adjuvant treatment of HR+, HER2−, node-positive, high-risk, early breast cancer (monarchE). J Clin Oncol. 2020;38(34):3987-3998. https://doi.org/10.1200/JCO.20.02514

    5Endocrine therapy with or without abemaciclib (LY2835219) following surgery in participants with breast cancer (monarchE). ClinicalTrials.gov identifier: NCT03155997. Updated January 24, 2022. Accessed October 1, 2021. https://clinicaltrials.gov/show/NCT03155997

    This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions.

    Date of Last Review: 08 August 2022


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