Duration of Response and Tumor Shrinkage with First-Line Ribociclib + Letrozole in Postmenopausal Women with HR+, HER2– ABC

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 (600 mg/day; 3 weeks on/1 week off) + LET (2.5 mg/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 with measurable 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 15.3 months, median DoR was not reached in either arm. Tumor shrinkage was evaluable in 443 (66%) pts. Pt characteristics were well-balanced in both arms and irrespective of tumor shrinkage, apart from de 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 arm experienced 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 arm at each tumor evaluation over the first 18 months.Table245PDQCut-offCorresponding best % change in tumor sizeRIB + LET n=231PBO + LET n = 212≤Q1≤25%At least –53%73 (32%)38 (18%)Q1–Q2>25% to ≤ 50%Between –53% and –33%64 (28%)52 (25%)Q2–Q3>50% to ≤ 75%Between –33% and –12%52 (23%)54 (25%)>Q3>75%Less than –12%42 (18%)68 (32%) Open table in a new tab 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. Clinical trial identification: NCT01958021 Legal entity responsible for the study: Novartis Pharmaceuticals Corporation Funding: Novartis Pharmaceuticals Corporation Disclosure: W. Janni: Research grants and/or honoraria from Sanofi-Aventis, Novartis, Roche, Pfizer, AstraZeneca, Chugai, GSK, Eisai, Cellgene, Johnson & Johnson. T. Bachelot: Research funding from Roche and Novartis; Consultant for AstraZeneca, Roche, Novartis, and Pfizer; travel from AstraZeneca, Roche, Novartis, Pfizer. F.J. Esteva: Research funds and consultancy/honoraria from Novartis. T.J. Pluard: Advisor for Novartis. S. Sutradhar: Novartis employee. M. Miller: Novartis employee and Novartis stocks/shares. M. Campone: Consultant/advisory role for Novartis, Pfizer, AstraZeneca, Roche, and Lilly. All other authors have declared no conflicts of interest.