Head-to-head comparison of palbociclib and ribociclib in first-line treatment of HR-positive/HER2-negative metastatic breast cancer with real-world data from the OPAL registry.

Cyclin-dependent kinase 4/6 inhibitors (CDKIs) in combination with endocrine therapy (ET) are the standard-of-care in the first-line treatment of HR-positive, HER2-negative metastatic breast cancer. In the absence of direct head-to-head trials comparing the efficacy and safety of the different CDKIs, the individual choice of treatment in everyday practice is complex. Inverse probability of treatment weighting was used to emulate a head-to-head comparison of palbociclib +ET (PALBO) and ribociclib +ET (RIBO) in patients recruited into the prospective, observational, multicenter registry platform OPAL (NCT03417115). Progression-free survival (PFS), overall survival (OS) and quality of life surveys were analyzed, also for subgroups stratified by treatment-free interval (TFI). A total of 623 patients with HR-positive, HER2-negative metastatic breast cancer received PALBO (n = 388) or RIBO (n = 235) in their first line of treatment. No difference between PALBO and RIBO was found for PFS (median 26.7 months [23.6, 30.7] vs. 27.0 months [21.1, 30.4], HR 1.01 [0.80, 1.27]) and OS (median 42.4 months [38.8, 50.3] vs. 49.3 months [36.9, NA], HR 0.96 [0.71, 1.28]). There was a trend for longer PFS and OS in patients with TFI <12 months receiving RIBO. Patients reported comparable side effects for both CDKIs. This head-to-head comparison revealed no difference in PFS and OS between PALBO and RIBO, however, a trend to longer PFS and OS with RIBO was observed in the subgroup of patients with TFI <12 months. Side effects experienced with PALBO and RIBO highlight the important toxicities to be addressed during treatment decision.