Adjuvant abemaciclib combined with endocrine therapy for high-risk early breast cancer: safety and patient-reported outcomes from the monarchE study

Abstract

Background: In monarchE, abemaciclib plus endocrine therapy (ET) as adjuvant treatment of hormone receptor-positive, human epidermal growth factor 2-negative, high-risk, early breast cancer (EBC) demonstrated a clinically meaningful improvement in invasive disease-free survival versus ET alone. Detailed safety analyses conducted at a median follow-up of 27 months and key patient-reported outcomes (PROs) are presented.

Patients and methods: The safety population included all patients who received at least one dose of study treatment (n = 5591). Safety analyses included incidence, management, and outcomes of common and clinically relevant adverse events (AEs). Patient-reported health-related quality of life, ET symptoms, fatigue, and side-effect burden were assessed.

Results: The addition of abemaciclib to ET resulted in higher incidence of grade ≥3 AEs (49.7% versus 16.3% with ET alone), predominantly laboratory cytopenias [e.g. neutropenia (19.6%)] without clinical complications. Abemaciclib-treated patients experienced more serious AEs (15.2% versus 8.8%). Discontinuation of abemaciclib and/or ET due to AEs occurred in 18.5% of patients, mainly due to grade 1/2 AEs (66.8%). AEs were managed with comedications (e.g. antidiarrheals), abemaciclib dose holds (61.7%), and/or dose reductions (43.4%). Diarrhea was generally low grade (grade 1/2: 76%); grade 2/3 events were highest in the first month (20.5%), most were short-lived (≤7 days) and did not recur. Venous thromboembolic events (VTEs) were higher with abemaciclib + ET (2.5%) versus ET (0.6%); in the abemaciclib arm, increased VTE risk was observed with tamoxifen versus aromatase inhibitors (4.3% versus 1.8%). PROs were similar between arms, including being 'bothered by side-effects of treatment', except for diarrhea. At ≥3 months, most patients reporting diarrhea reported 'a little bit' or 'somewhat'.

Conclusions: In patients with high-risk EBC, adjuvant abemaciclib + ET has an acceptable safety profile and tolerability is supported by PRO findings. Most AEs were reversible and manageable with comedications and/or dose modifications, consistent with the known abemaciclib toxicity profile.

Trial registration: ClinicalTrials.gov NCT03155997.

Keywords: HER2 negative; HR positive; abemaciclib; early breast cancer; monarchE; safety.

Conflict of interest statement

Disclosure HSR reports grants from Pfizer, Novartis, Eli Lilly and Company, Genentech/Roche, Macrogenics, Merck, Boehringer Ingelheim, Polyphor, OBI, Odonate, Daiichi, Astra Zeneca, Seattle Genetics, Immunomedics, Sermonix; personal fees from Mylan, Puma, Samsung outside the submitted work. JO reports personal fees from AbbVie Inc., Agendia, Amgen Biotechnology, Aptitude Health, AstraZeneca, Bayer, Bristol-Myers Squibb, Celgene Corporation, Clovis Oncology, Daiichi Sankyo, Eisai, G1 Therapeutics, Gilead Sciences, GRAIL, Halozyme Therapeutics, Heron Therapeutics, Immunomedics, Ipsen Biopharmaceuticals, Eli Lilly and Company, Merck, Myriad, Nektar Therapeutics, Novartis, Pfizer, Pharmacyclics, Pierre Fabre Pharmaceuticals, Puma Biotechnology, Prime Oncology, Roche/Genentech, Samsung Bioepis, Sanofi, Seagen, Seattle Genentech, Syndax Pharmaceuticals, Taiho Oncology, Takeda, Synthon outside the submitted work. FB reports personal fees for honoraria and advisory role for Roche, Pfizer, Eli Lilly and Company, and Novartis outside the submitted work. MT reports research grants from JBCRG association, Astellas, AFI technologies, Shionogi, and GL Science; research grants and personal fees from Chugai, Takeda, Pfizer, Kyowa-Kirin, Taiho, Eisai, Daiichi-Sankyo, AstraZeneca, Shimadzu, Yakult, and Nippon Kyaku; other fees from Kyowa-Kirin and Daiichi-Sankyo; personal and other fees from Eli Lilly and Company, Konica Minolta, Bristol Myers Squibb, Athenex Oncology, Bertis Terumo, and Kansai Medical Net; personal fees for honoraria from MSD, Exact Science, and Novartis; and serves as a board of director for JBCRG association, Organisation for Oncology and Translational Research, and Kyoto Breast Cancer Research Network, outside the submitted work. IB reports grants and research support to institution: AstraZeneca, Roche and Eli Lilly and Company; personal fees for honoraria and advisory role from AstraZeneca, Roche, Novartis, Eisai, Celgene, Pfizer, Eli Lilly and Company, Pierre Fabre and Bristol-Myers Squibb, Veracyte outside the submitted work. MG reports personal fees from MSD, Novartis, GenDrug, and Amgen, outside the submitted work. TY reports grant and other fees from Chugai, Taiho, Nippon Kayaku, Kyowa Kirin; other fees from Eisai, Novartis Pharma, Astra Zeneca, Eli Lilly and Company, Daiichi Sankyo, and Pfizer Japan outside the submitted work. FZ reports personal fees for honoraria, fees for lectures and advisory role for Astra Zeneca, Daiichi, Eli Lilly and Company, Merck, Novartis, Pfizer, and Roche outside the submitted work. MC reports personal fees from Eli Lilly and Company, Novartis, and GT1; other fees from AstraZeneca, Sanofi, Servier, AbbVie, Accord, Pfizer, Seagen, and Daichii Sankyo, outside of the submitted work. BSA, AS, MH, JB, AZ, RW are full-time employees of Eli Lilly and Company and/or Eli Lilly and Company shareholders. SRDJ reports personal fees from AstraZeneca, Eli Lilly and Company, Novartis, Pfizer, Puma Biotechnology, Eisai, and Roche/Genentech; personal fees and other from AstraZeneca, Eli Lilly and Company, Novartis, Pfizer, Puma Biotechnology, and Roche/Genentech, outside the submitted work. MR reports personal fees from Pfizer, Novartis, Eli Lilly and Company, Roche Pharma AG, AstraZeneca, Daiichi Sankyo, Hexal, Novartis, SOMATEX, Seagen, and Pfizer; other fees from Pfizer, Celgene, and Novartis, outside the submitted work. SMT reports grants and personal fees from Eli Lilly and Company during the conduct of the study; grants and personal fees from AstraZeneca, Eli Lilly and Company, Merck, Nektar, Novartis, Pfizer, Genentech/Roche, Exelixis, Bristol-Myers Squibb, Eisai, Nanostring, Sanofi, Odonate, Immunomedics/Gilead; grants from Cyclacel; personal fees from Puma, Celldex, Seattle Genetics, Silverback Therapeutics, G1 Therapeutics, Athenex, OncoPep, Kyowa Kirin Pharmaceuticals, Daiichi Sankyo, CytomX, Samsung Bioepsis Inc., Certara, Mersana Therapeutics, OncoSec, Ellipses Pharma, 4D Pharma, Chugai Pharma, Infinity Therapeutics, BeyondSpring Pharmaceuticals outside the submitted work. All other authors have declared no conflicts of interest. Data sharing Lilly provides access to all individual participant data collected during the trial, after anonymization, with the exception of pharmacokinetic or genetic data. Data are available to request 6 months after the indication studied has been approved in the United States and European Union or after primary publication acceptance, whichever is later. No expiration date for data requests is set once the data are made available. Access is provided after a proposal has been approved by an independent review committee identified for this purpose and after receipt of a signed data-sharing agreement. Data and documents, including the study protocol, statistical analysis plan, clinical study report, and blank or annotated case report forms, will be provided in a secure data-sharing environment. For details on submitting a request, see the online instructions.

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