MONARCH 3: Abemaciclib as initial therapy for patients with HR+/HER2- advanced breast cancer

Abstract

Purpose: MONARCH 3 evaluates abemaciclib+non‐steroidal aromatase inhibitors (NSAI) anastrozole (A) or letrozole (L) as initial therapy in HR+/ HER2‐advanced breast cancer (ABC). Methods: MONARCH 3 is a double‐blind, Phase 3 study of abemaciclib+ NSAI (A or L) vs placebo (P)+NSAI in postmenopausal women with HR+/HER2‐ ABC who had no prior systemic therapy in the metastatic setting. Endocrine naive pts or pts with disease relapse >12 months after (neo)adjuvant endocrine therapy (ET) were randomized 2:1 and stratified by metastatic site (visceral/ bone only/other) and prior ET (AI vs no ET vs other). Pts received abemaciclib/P (150 mg, twice daily continuous schedule) + 1 mg A or 2.5 mg L, daily. Primary objective: investigator‐assessed PFS. Secondary objectives included objective response rate (ORR) and safety. Results: 493 women were randomized to abemaciclib+NSAI (n = 328) or P+NSAI (n = 165). Pt characteristics were: visceral disease (52.9%), measurable disease (80.5%), prior (neo)adjuvant AI (27.4%), and de novo ABC (39.8%). At the interim analysis, 194 PFS events were observed. PFS was significantly prolonged with a hazard ratio of 0.543 (95% CI, 0.409 to 0.723, P = 0.000021; median PFS: not reached in abemaciclib arm, 14.7 months in P arm). In pts with measurable disease, the ORR was 59% in the abemaciclib arm and 44% in the P arm (P = 0.004). The most frequent AEs were (abemaciclib vs P arms) diarrhea (81.3% grade 3: 9.5%, no grade 4] vs 29.8% grade 3: 1.2%, no grade 4]), neutropenia (41.3% grade 3/4: 21.1%] vs 1.9% grade 3/4: 1.2%]), and fatigue (40.1% grade 3: 1.8%] vs 31.7% grade 3: 0%]). Conclusions: Abemaciclib+NSAI demonstrated a tolerable safety profile and was an effective initial treatment for pts with HR+/HER2‐ ABC, significantly improving PFS and ORR.