Comparative observational study of real-world outcomes with first-line CDK4/6 inhibitors plus endocrine therapy for HR+/HER2- advanced breast cancer

The real-world observational PALMARES-2 study, at 18 centers in Italy, compared the three CDK4/6 inhibitors palbociclib, ribociclib, and abemaciclib in combination with endocrine therapy as first-line therapy for HR-positive/HER2-negative advanced breast cancer (HR+ HER2- aBC). Among all patients, the median real-world progression-free survival (rwPFS) was 34.1 months, whereas abemaciclib (aHR 0.76; p=0.004) and ribociclib (aHR 0.83; p=0.007) were associated with better rwPFS compared with palbociclib. In patients with endocrine-sensitive disease, only abemaciclib was associated with better rwPFS compared to palbociclib. On the other hand, abemaciclib and ribociclib were more effective than palbociclib in patients who were premenopauzal or had endocrine-resistant or luminal B-like disease, while abemaciclib was more effective than ribociclib and palbociclib in patients with de novo metastatic disease, and more effective than palbociclib in patients with poorer ECOG performance status. The authors conclude that the three CDK4/6 inhibitors have different real-world effectiveness among various subgroups of patients with HR+ HER2-aBC.