Dieras V, et al. - Researchers performed a longitudinal analysis of pooled, longer-term PALOMA data regarding the safety of palbociclib administered with endocrine therapy for HR+/HER2- advanced breast cancer. Palbociclib in combination with endocrine therapy was tolerable when the overall incidence of toxicities was analyzed separately in three PALOMA studies. The long-term safety analyses did not provide any evidence of specific cumulative or delayed toxicities with palbociclib plus endocrine therapy. This finding supports the ongoing study of palbociclib plus endocrine therapy in early breast cancer.

Methods

• Researchers pooled data from three randomized phase II and III studies of hormone receptor–positive/human epidermal growth factor receptor 2–negative advanced breast cancer patients.
• Random assignment of front-line patients to receive letrozole with/without palbociclib (PALOMA-1) or letrozole plus palbociclib/placebo (PALOMA-2) was carried out.
• In PALOMA-3, fulvestrant plus palbociclib/placebo was administered to patients with prior endocrine resistance.
• Assessment of the cumulative event rates of adverse events (AEs), up to 50 months of treatment, was carried out over time.

Results

• This pooled analysis included patients treated with endocrine therapy (n=1,343) (872 were also treated with palbociclib, and 471 were not).
• Neutropenia and infections (any grade, 80.6% and 54.7%, respectively) were documented as the most commonly detected AEs with palbociclib plus endocrine therapy; these AEs were higher than in the endocrine monotherapy arm (any grade, 5.3% and 36.9%).
• In the initial months of the study, reporting of the most common hematologic AEs (≥ 15.0% in the palbociclib arm) was more likely; after this time period the cumulative event rate did not substantially increase.
• Any grade AEs that led to permanent discontinuation of palbociclib plus endocrine therapy over three years was reported in only 8.3% of patients.