RESUMO
INTRODUCTION: Palbociclib is a widely used treatment for advanced breast cancer in older adults. However, the existing evidence regarding its safety and tolerability in this age group is inconsistent and limited to retrospective subgroup or pooled analyses. MATERIALS AND METHODS: We conducted a prospective single-arm multicenter phase 2 study to evaluate the safety and tolerability of palbociclib in participants aged 70 years or older with advanced hormone receptor-positive breast cancer. Participants were given palbociclib in combination with their physician's choice of endocrine therapy (letrozole or fulvestrant). The primary endpoint was the incidence of grade 3+ adverse events (AEs) by six months. Secondary endpoints included AE-related dose delays, dose reductions, early discontinuations, and hospitalizations. Additionally, we compared these endpoints by age groups (70-74 and ≥ 75 years). RESULTS: Of the 90 participants (median age 74 years [70-87]) enrolled, 75.6% (95% confidence interval [CI], 65.4-84.0) had grade 3+ AEs by six months. The most frequent grade 3+ AEs were neutropenia (61%), fatigue (4%), and nausea (3%). Febrile neutropenia was uncommon (1.1%). Due to AEs, 36% had dose delays, 34% had dose reductions, 10% had early discontinuations, and 10% had hospitalizations. Compared to those aged 70-74 years, participants aged ≥75 years had higher rates of early discontinuations (5.9% vs 15.9%, a difference of 9.5% [95% CI 3.5%-22.5%]). DISCUSSION: Palbociclib has an overall favorable safety profile in adults aged ≥70 with advanced breast cancer. However, adults ≥75 years had a trend toward higher rates of AE-related early discontinuations compared to those 70-74 years. Further research is needed to evaluate tolerability and improve the delivery of palbociclib in older adults. CLINICALTRIALS: gov:NCT03633331.