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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

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.
   
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