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Clinical Trial
. 2021 Jun;21(3):181-190.e2.
doi: 10.1016/j.clbc.2020.09.011. Epub 2020 Sep 30.

nextMONARCH: Abemaciclib Monotherapy or Combined With Tamoxifen for Metastatic Breast Cancer

Erika Hamilton  1 , Javier Cortes  2 , Ozgur Ozyilkan  3 , Shin-Cheh Chen  4 , Katarina Petrakova  5 , Aleksey Manikhas  6 , Guy Jerusalem  7 , Roberto Hegg  8 , Jens Huober  9 , Sonya C Chapman  10 , Yi Lu  10 , Molly C Hardebeck  10 , Melissa M Bear  10 , Erica L Johnston  10 , Miguel Martin  11
Affiliations
Clinical Trial

nextMONARCH: Abemaciclib Monotherapy or Combined With Tamoxifen for Metastatic Breast Cancer

Erika Hamilton et al. Clin Breast Cancer. 2021 Jun.

Abstract

Background: Abemaciclib is a selective cyclin-dependent kinase 4 and 6 inhibitor administered continuously for hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer. Abemaciclib is associated with dose-dependent early-onset diarrhea. nextMONARCH evaluated abemaciclib monotherapy (with or without prophylactic loperamide) and combined with tamoxifen for endocrine refractory metastatic breast cancer (MBC) after chemotherapy.

Patients and methods: nextMONARCH is an open-label, controlled, randomized, phase II study of women with endocrine-refractory HR+, HER2- MBC previously treated with chemotherapy. Patients received abemaciclib 150 mg plus tamoxifen 20 mg (A+T), abemaciclib 150 mg every 12 hours (A-150), or abemaciclib 200 mg plus prophylactic loperamide (A-200). The primary objective was progression-free survival (PFS). PFS analyses tested superiority of A+T to A-200 and informal noninferiority of A-150 to A-200. The secondary objectives included the objective response rate (ORR), safety, and pharmacokinetics.

Results: The median PFS was 9.1 months for A+T versus 7.4 months for A-200 (hazard ratio, 0.815; 95% confidence interval, 0.556-1.193; P = .293). The A-200 PFS was comparable to that with A-150 at 6.5 months (hazard ratio, 1.045; 95% confidence interval, 0.711-1.535; P = .811). The ORR was 34.6%, 24.1%, and 32.5% for A+T, A-150, and A-200, respectively. No new safety signals were identified. The incidence and severity of diarrhea (62.3%; grade 3, 7.8%) with A-200 was similar to that with A-150 (67.1%; grade 3, 3.8%). The pharmacokinetics were comparable to previous observations.

Conclusions: The addition of tamoxifen to abemaciclib did not significantly improve PFS or ORR compared with abemaciclib monotherapy but confirmed the single-agent activity of abemaciclib in heavily pretreated HR+, HER2- MBC. Dose reductions and antidiarrheal medication generally managed diarrhea while maintaining efficacy.

Keywords: Cyclin-dependent kinase 4 and 6; Endocrine therapy; HER2(−); Hormone receptor-positive; MBC.

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