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.
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