nextMONARCH Phase 2 randomized clinical trial: overall survival analysis of abemaciclib monotherapy or in combination with tamoxifen in patients with endocrine-refractory HR + , HER2- metastatic breast cancer

Abstract

Purpose: Resistance to endocrine therapy poses a major clinical challenge for patients with hormone receptor-positive (HR +), human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (MBC). We present the preplanned 24-month final overall survival (OS) results, alongside updated progression-free survival (PFS), and objective response rate (ORR) results.

Methods: nextMONARCH is an open-label, controlled, randomized, Phase 2 study of abemaciclib alone or in combination with tamoxifen in women with endocrine-refractory HR + , HER2- MBC previously treated with chemotherapy. Patients were randomized 1:1:1 to: abemaciclib 150 mg and tamoxifen 20 mg (A + T), abemaciclib 150 mg (A-150), or abemaciclib 200 mg and prophylactic loperamide (A-200). OS was the main prespecified secondary endpoint. PFS, ORR, and safety at 24 months were compared to previously reported primary analysis results.

Results: Of the 234 patients enrolled, 12 were receiving study treatment at data cutoff (28Jun2019). Median follow-up was 27.2 months. Median OS was 24.2 months in the A + T arm, 20.8 months in A-150, and 17.0 months in A-200 (A + T versus A-200: HR 0.62; 95%CI [0.40, 0.97], P = 0.03 and A-150 versus A-200: HR 0.96; 95%CI [0.64, 1.44], P = 0.83). PFS and ORR results at 24 months were consistent with the primary analysis. The safety profile corresponded with previous reports.

Conclusion: The addition of tamoxifen to abemaciclib demonstrated greater OS benefit than monotherapy. This study confirmed the single-agent activity of abemaciclib in heavily pretreated women with endocrine-refractory HR + , HER2- MBC, as well as the previously reported primary PFS and ORR results, with no new safety signals observed. Trial Registration ClinicalTrials.gov Identifier: NCT02747004.

Keywords: Cyclin-dependent kinase 4 and 6; Endocrine therapy; HER2-negative; Hormone receptor-positive; MBC; Overall survival.

Conflict of interest statement

E.H. is a full-time employee of Sarah Cannon Research Institute. J.C. declares Consulting/Advisor: Roche, Celgene, Cellestia, AstraZeneca, Seattle Genetics, Daiichi Sankyo, Erytech, Athenex, Polyphor, Lilly, Merck Sharp&Dohme, GSK, Leuko, Bioasis, Clovis Oncology, Boehringer Ingelheim, Ellipses, Hibercell, BioInvent, Gemoab, Gilead, Menarini, Zymeworks, Reveal Genomics; Honoraria: Roche, Novartis, Celgene, Eisai, Pfizer, Samsung Bioepis, Lilly, Merck Sharp&Dohme, Daiichi Sankyo; Stock, patents and intellectual property: MedSIR, Nektar Pharmaceuticals; and Travel, accommodation, expenses: Roche, Novartis, Eisai, pfizer, Daiichi Sankyo, Astrazeneca. O.O. has nothing to declare. S-C.C. has nothing to declare. K.P. has nothing to declare. A.M. has nothing to declare. G.J. declares Non-Financial Support from Eli Lilly and company during the conduct of the study; Grants, Personal Fees and Non-Financial Support: Novartis, Roche, Pfizer; Personal Fees and Non-Financial Support: Eli Lilly and company, Amgen, BMS, Astra-Zeneca; Personal Fees: Abbvie, Seagen, Daiichi-Sankyo; Non-Financial Support: Medimmune, MerckKGaA outside the submitted work. R.H. has nothing to declare. J.H. declares Research Funding: Celgene, Novartis, Hexal, Lilly; Honoraria: Lilly, Novartis, Roche, Pfizer, AstraZeneca, MSD, Celgene; Eisai, Abbvie, Seagen, Gilead; Consulting, advisory relationship: Lilly, Novartis, Roche, Pfizer, Hexal, AstraZeneca, MSD, Celgene, Abbvie, Seagen, Gilead; and Travel expenses: Roche, Pfizer, Novartis, Celgene, Daiichi. W.Z. was a full-time employee of Eli Lilly and Company at the time of the study and is an Eli Lilly and Company shareholders. Y.C.is a full-time employee of Eli Lilly and Company and Eli Lilly and Company shareholders. M.M. declares Research Grants: Roche, PUMA and Novartis; Consulting/Advisory fees: AstraZeneca, Amgen, Taiho Oncology, Roche/Genentech, Novartis, PharmaMar, Eli Lilly and Company, PUMA, Taiho Oncology, Daiichi Sankyo and Pfizer; and Speakers’ honoraria: AstraZeneca, Eli Lilly and Company, Amgen, Roche/Genentech, Novartis, and Pfizer.

© 2022. The Author(s).

Figures

Fig. 1

Kaplan–Meier curves of survival in the intent-to-treat population, a overall survival at 24 months and b progression free survival at 183 events

Fig. 2

Sub-group analysis of overall survival in the intent-to-treat population. Overall survival unstratified hazard ratios (HR) and 95% confidence intervals are shown with diamond size proportional to the number of patients in each sub-group. Factor levels with ABC advanced breast cancer, A + T abemaciclib 150 mg plus tamoxifen, A-150 abemaciclib 150 mg, A-200 abemaciclib 200 mg plus prophylactic loperamide, CI confidence internal, HR hazard ratio, n number of subjects in the subgroup, PS performance status, T tamoxifen

Fig. 3

Best percentage change in tumor size from baseline, each bar representing individual patients with measureable disease. A + T abemaciclib 150 mg plus tamoxifen, A-150 abemaciclib 150 mg, A-200 abemaciclib 200 mg plus prophylactic loperamide, CBR clinical benefit rate, N total number of patients randomized, ORR objective response rate