Kantonsspital St.Gallen

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

Erika Hamilton, Javier Cortes, Ozgur Ozyilkan, Shin-Cheh Chen, Katarina Petrakova, Aleksey Manikhas, Guy Jerusalem, Roberto Hegg, Jens Huober, Sonya C Chapman, Yi Lu, Molly C Hardebeck, Melissa M Bear, Erica L Johnston & Miguel Martín


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.

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.

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.

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.
citation Hamilton E, Cortes J, Ozyilkan O, Chen S C, Petrakova K, Manikhas A, Jerusalem G, Hegg R, Huober J, Chapman S C, Lu Y, Hardebeck M C, Bear M M, Johnston E L, Martín M. nextMONARCH: Abemaciclib Monotherapy or Combined With Tamoxifen for Metastatic Breast Cancer. Clin Breast Cancer 2020;.
type journal paper/review (English)
date of publishing 30-09-2020
journal title Clin Breast Cancer
ISSN electronic 1938-0666
PubMed 33148479
DOI 10.1016/j.clbc.2020.09.011