MONARCH 3 final PFS: a randomized study of abemaciclib as initial therapy for advanced breast cancer

Stephen Johnston, Miguel Martin, Angelo Di Leo, Seock-Ah Im, Ahmad Awada, Tammy Forrester, Martin Frenzel, Molly C Hardebeck, Joanne Cox, Susana Barriga, Masakazu Toi, Hiroji Iwata, Matthew P Goetz, Stephen Johnston, Miguel Martin, Angelo Di Leo, Seock-Ah Im, Ahmad Awada, Tammy Forrester, Martin Frenzel, Molly C Hardebeck, Joanne Cox, Susana Barriga, Masakazu Toi, Hiroji Iwata, Matthew P Goetz

Abstract

At the MONARCH 3 interim analysis, abemaciclib plus a nonsteroidal aromatase inhibitor (AI) significantly improved progression-free survival (PFS) and objective response rate (ORR) with a tolerable safety profile as initial treatment for hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC). MONARCH 3 is a randomized, phase III, double-blind study of abemaciclib/placebo (150 mg twice daily, continuous) plus nonsteroidal AI (1 mg anastrozole or 2.5 mg letrozole, daily). A total of 493 postmenopausal women with HR+, HER2- ABC with no prior systemic therapy in this setting were enrolled. The primary endpoint was investigator-assessed PFS (final analysis after 240 events); other endpoints included response and safety evaluations. Here we analyze the final PFS data and update secondary endpoints. The abemaciclib arm had a significantly longer median PFS than the placebo arm (28.18 versus 14.76 months; hazard ratio [95% confidence interval], 0.540 [0.418-0.698]; p = .000002). The ORR was 61.0% in the abemaciclib arm versus 45.5% in the placebo arm (measurable disease, p = .003). The median duration of response was longer in the abemaciclib arm (27.39 months) compared to the placebo arm (17.46 months). The safety profile was consistent with previous reports. The most frequent grade ≥ 3 adverse events in the abemaciclib versus placebo arms were neutropenia (23.9% versus 1.2%), diarrhea (9.5% versus 1.2%), and leukopenia (8.6% versus 0.6%). Abemaciclib plus a nonsteroidal AI was an effective initial treatment with an acceptable safety profile for HR+, HER2- ABC.

Conflict of interest statement

S.J. is a consultant/independent contractor for AstraZeneca, Novartis, Pfizer, OBI, and Eli Lilly and Company; receives grants/research support from Pfizer; and is on the Speaker’s Bureau for OBI and Puma. M.M. is a consultant/independent contractor AstraZeneca, Novartis, Roche-Genentech, Pfizer, Glaxo, Pharmamar, Taiho Oncology and Eli Lilly and Company; and have received research grants from Novartis and Roche. D.L. has been a consultant/independent contractor for Amgen, Roche, Novartis, Pfizer, AstraZeneca, Eli Lilly and Company, Pierre Fabre, Bayer, Celgene, Puma Biotechnology, and Daichii-Sankyo; has received grant/research support from Novartis, Pfizer, and AstraZeneca; honorarium from Roche, Novartis, Pfizer, AstraZeneca, Genomic Health, Eisai, Eli Lilly and Company, Pierre Fabre, Bayer, Celgene, and Daichii-Sankyo; and received travel/accommodations/expenses from Roche, Novartis, Pfizer, AstraZeneca, Eisai, Eli Lilly and Company, Pierre Fabre, Bayer, Celgene, Puma Biotechnology, and Daichii-Sankyo. S.I. receives grants/research support from AstraZeneca and is an advisory/board member for AstraZeneca, Eisai, Hanmi, Novartis, Pfizer and Roche. A.A. is an advisor/board member for Roche, Pfizer, Eli Lilly and Company, Eisai, Novartis, MSD, and BMS. T.F. is a full-time employee and stock shareholder of Eli Lilly and Company. M.F. is a full-time employee and stock shareholder of Eli Lilly and Company. M.C.H. is a full-time employee and stock shareholder of Eli Lilly and Company. J.C. is a full-time employee of Eli Lilly and Company. S.B. is a full-time employee of Eli Lilly and Company. M.T. is a consultant/independent contractor for Kyowa-Hakko Kirin; received grant/research support from Novartis, AstraZeneca, Taiho Pharma, Chugai Pharmaceutical Co. Ltd., Pfizer, and Eli Lilly and Company; served on an advisory board for Genomic Health Inst; received honorarium from Novartis, MSD, Takeda, AstraZeneca, Taiho Pharma, Chugai Pharmaceutical Co. Ltd., Pfizer, Eisai, Eli Lilly and Company, Kyowa-Hakko Kirin, and Genomic Health Inst.; and received travel funds/accommodations/expenses from Genomic Health Inst. and Eli Lilly and Company. H.I. is a consultant/independent contractor for Pfizer, Daiichi-Sankyo, and AstraZeneca; received grants/research support from Eli Lilly and Company, Chugai, Pfizer, Daiichi-Sankyo, AstraZeneca, Novartis, Bayer, and MSD; is an advisor/board member for Eli Lilly and Company, Chugai, and Daiichi-Sankyo; and received honorarium from Chugai, Pfizer, Eisai, Daiichi-Sankyo, and AstraZeneca. M.P.G. has been a consultant for Eli Lilly and Company, bioTheranostics, Novartis, Genomic Health, Eisai, Biovica, and Sermonix; and received research funding from Eli Lilly and Company, and Pfizer.

Figures

Fig. 1
Fig. 1
Progression-free survival. a Investigator-assessed and b Independent central review in the intent-to-treat population. NR, not reached
Fig. 2
Fig. 2
Subgroup analysis of progression-free survival. ECOG PS, Eastern Cooperative Oncology Group Performance Status
Fig. 3
Fig. 3
Tumor response for patients with measurable disease. a Best percent change in tumor size. b Mean: percentage change in tumor size from baseline by cycle
Fig. 4
Fig. 4
Patient response to treatment. a Median time to response for patients with measurable disease (investigator assessment). b Duration of response. c Probability of response in patients with measurable disease

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