254P - Matching-adjusted indirect treatment comparison of ribociclib and palbociclib as first-line treatments for HR+, HER2– ABC

Abstract

Background: Ribociclib (RIB) and palbociclib (PAL) combinations with letrozole (LET) vs LET alone have been evaluated in separate Phase 3 randomized controlled trials in patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2–) advanced breast cancer (ABC); however, no head-to-head comparative studies have been conducted. Classic indirect treatment comparison (ITC) can lead to biased results due to differences in patient populations and trial designs. These differences can be corrected by using the matching-adjusted indirect comparisons (MAIC) technique. Here, we compare RIB and PAL in patients with HR+, HER2– ABC using MAIC. Methods: Individual patient data were available for the RIB trial (MONALEESA-2). As only published summary data were available for the PAL trial (PALOMA-2), RIB data were adjusted to closely match the PAL data. Data for RIB-treated patients were assigned weights so that weighted mean baseline characteristics matched those reported for PAL. Overall survival data have not been reported for PALOMA-2, thus only progression-free survival (PFS) data were compared. Adjusted hazard ratios (HRs) for PFS were calculated using weighted Cox regression models and used to calculate indirect HRs with 95% confidence intervals (CIs). Classic frequentist ITC was performed before and after adjustment. ITC of Grade 3/4 adverse events (AEs) was also performed. Results: The unadjusted PFS HR (95% CI) for RIB+LET vs LET was 0.556 (0.429; 0.721) and for PAL+LET vs LET was 0.580 (0.460; 0.720). MAIC adjustment for age, race, region, Eastern Cooperative Oncology Group status, disease stage at diagnoses, sites of metastases, and chemotherapy setting at baseline provided a RIB+LET vs LET HR estimate of 0.501 (0.365; 0.688). The HR for unadjusted ITC of RIB vs PAL was 0.959 (0.681; 1.350) and by MAIC was 0.864 (0.586; 1.274). ITC of Grade 3/4 AEs yielded a risk ratio (RR) of 0.81 (0.61; 1.08) for RIB vs PAL. Conclusions: Using MAIC methodology due to a lack of head-to-head trials, the resulting HRs for PFS were comparable. Similarly, using ITC, AE profiles were also comparable although the RR for AEs slightly favored RIB. Legal entity responsible for the study: Novartis Pharmaceuticals Corporation Funding: Novartis Pharmaceuticals Corporation Disclosure: A. Forsythe: Consultant for Novartis. D. Chandiwana, M. Monaco: Novartis employee and stocks/shares. All other authors have declared no conflicts of interest.