Duration of response and tumor shrinkage with first-line ribociclib + letrozole in postmenopausal women with HR+, HER2– ABC

Abstract

Background: The Phase 3 MONALEESA‐2 study (NCT01958021) demonstrated that addition of ribociclib (RIB; cyclin‐dependent kinase 4/6 inhibitor) to letrozole (LET) significantly improved progression‐free survival (PFS) in patients (pts) with hormone receptor‐positive (HR+), HER2‐negative (HER2‐) advanced breast cancer (ABC). RIB benefit was observed as early as 8 weeks. Here we evaluate duration of response (DoR) and tumor shrinkage. Methods: Postmenopausal women (N=668) with HR+, HER2‐ ABC and no prior systemic therapy for ABC were randomized to RIB (600mg/day; 3 weeks on/1 week off) +LET (2.5mg/day; continuous) or placebo (PBO) + LET. Pts had measurable disease or≥ 1 predominantly lytic bone lesion. Primary endpoint was PFS; DoR was an exploratory endpoint. Tumor assessments were conducted every 8 weeks for the first 18 months. For tumor shrinkage analyses, pts were grouped by quartiles (Q) for best%change in target lesion; pts were excluded from this analysis if best% change was unavailable or contradicted by overall response of unknown/progressive disease. Results: Of 501 pts withmeasurable disease, 135 (53%) vs 91 (37%) pts had a complete response or partial response in the RIB +LET vs PBO + LET arm, respectively. At a median follow‐up of 15.3months, median DoR was not reached in either arm. Tumor shrinkage was evaluable in 443 (66%) pts. Pt characteristics were wellbalanced in both arms and irrespective of tumor shrinkage, apart fromde novo ABC in Q2‐Q3 (RIB + LET vs PBO + LET; 46% vs 30%) and visceral disease in ≤Q1 (64% vs 84%). A higher proportion of pts in the RIB + LET vs PBO + LET armexperienced a best%change of at least 53% (Table). In all evaluable pts, mean%change in tumor size was greater in the RIB + LET vs PBO + LET armat each tumor evaluation over the first 18months. Conclusions: In postmenopausal women with HR+, HER2‐ ABC, first‐line RIB+ LET prolonged PFS and was associated with a greater degree of tumor shrinkage vs PBO +LET. (Table Presented).