Updated results from MONALEESA-2, a phase 3 trial of first-line ribociclib + letrozole in hormone receptor-positive (HR+), HER2-negative (HER2–) advanced breast cancer (ABC)

Abstract

Background: In MONALEESA-2 (NCT01958021), patients (pts) with HRþ, HER2À ABC who received first-line ribociclib (RIBO; cyclin-dependent kinase 4/6 inhibitor) þ letrozole (LET) had a significant improvement in progression-free survival (PFS) compared with placebo (PBO) þ LET at the first analysis (Hortobagyi G, et al. N Engl J Med. 2016;375(18):1738-1748). Here we report updated efficacy and safety data from MONALEESA-2, with an additional 11 months follow-up (median follow-up duration of 26.4 months). Methods: MONALEESA-2 is a randomized (1:1) phase 3 trial evaluating RIBO (600 mg/day, 3-weeks-on/1-week-off) þ LET (2.5 mg/day, continuous) vs PBO þ LET in postmenopausal women with HRþ, HER2À ABC with no prior therapy for advanced disease. The primary endpoint was locally assessed PFS. Secondary endpoints included overall survival (OS; key), overall response rate (ORR), clinical benefit rate (CBR), and safety. Results: 668 pts were enrolled (RIBO þ LET: 334; PBO þ LET: 334). The updated PFS analysis confirmed treatment benefit from the combination of RIBO þ LET (hazard ratio ¼ 0.568; 95% CI: 0.457-0.704; P ¼ 9.63x10 À8). Median PFS with RIBO þ LET was 25.3 months (95% CI: 23.0-30.3) vs 16.0 months (95% CI: 13.4-18.2) with PBO þ LET. Treatment benefit was consistent across all pt subgroups, including age, prior therapies, de novo ABC, and visceral metastasis. OS results remained immature. Common grade 3/4 adverse events (¼15% of pts; RIBO þ LET vs PBO þ LET) included decreased neu-trophils (62.6% vs 1.5%), decreased leukocytes (36.8% vs 1.5%), and decreased lym-phocytes (16.2% vs 3.9%). Conclusions: Despite a long median PFS with PBO þ LET, the updated analyses confirmed that first-line treatment with RIBO þ LET significantly prolongs PFS in postme-nopausal women with HRþ, HER2À ABC. The safety profile of RIBO þ LET remains manageable.