Renate Haidinger, Brustkrebs Deutschland e.v. im Interview mit Prof. Dr. med. Michael Untch, Berlin-Buch
Thema: CDK4-6 Inhibitoren beim metastasierten Brustkrebs:
A. Di Leo et al. 236O_PR - MONARCH 3: Abemaciclib as initial therapy for patients with HR+/HER2- advanced breast cancer
Abemaciclib is an oral selective CDK4 & 6 inhibitor dosed on a continuous schedule and has demonstrated efficacy and tolerability as monotherapy and in combination with fulvestrant in patients (pts) with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC). MONARCH 3 evaluates abemaciclib plus the non-steroidal aromatase inhibitors (NSAI) anastrozole (A) or letrozole (L) as initial therapy in HR+/HER2- ABC.
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 have had no prior systemic therapy in the metastatic setting. Endocrine naïve 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, or 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. The primary objective was investigator-assessed progression-free survival (PFS). Secondary objectives included objective response rate (ORR) and safety. The study was powered to 80% at 1-sided α=.025 assuming a hazard ratio (HR) of 0.67 in favor of abemaciclib + NSAI, with analyses at 189 and 240 PFS events.
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. The PFS was significantly prolonged with a HR of 0.543 (95% CI, 0.409 to 0.723, P=.000021; median PFS: not reached in abemaciclib arm, 14.7 months in placebo arm). In pts with measurable disease, the ORR was 59% in the abemaciclib arm and 44% in the P arm (P=.004). The most frequent adverse events 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%]).
Abemaciclib + NSAI demonstrated a tolerable safety profile and was an effective initial treatment for pts with HR+/HER2- ABC, significantly improving PFS and ORR.
Clinical trial identification
Legal entity responsible for the study
Eli Lilly and Company
Eli Lilly and Company