Pooled analysis of addition of palbociclib to endocrine therapy for HR+/HER2-0 and HR+/HER2-low metastatic breast cancer

The combination of CDK4/6 inhibitors with endocrine therapy (ET) is the recommended first-line treatment for HR-positive/HER2-negative metastatic breast cancer (mBC). Pooled analysis of the PALOMA-2 and PALOMA-3 trials investigated the benefit of adding a CDK4/6 inhibitor to ET in the HER2-negative (0) and HER2-low-positive mBC subgroups. In the HER2-0 population, no significant difference in PFS was observed between palbociclib-letrozole and placebo-letrozole in PALOMA-2 (p=0.34), while in the HER2-low-positive population, palbociclib-letrozole was associated with a significantly lower risk of PFS-events than placebo-letrozole (HR 0.52; p<0.001) in PALOMA-2. In PALOMA-3, including patients who had progressed on previous ET, in the HER2-0 population, palbociclib-fulvestrant showed a significantly longer PFS than placebo-fulvestrant (HR 0.54; p=0.034), while in the HER2-low-positive subgroup, palbociclib-fulvestrant also improved PFS compared to placebo-fulvestrant (HR 0.39; p<0.0001). The authors conclude that addition of palbociclib to ET significantly improved PFS in HER2-low-positive patients, while HER2-0 patients only derived benefit from this addition after progression on previous ET.