Long-Term Pooled Safety Analysis of Palbociclib in Combination With Endocrine Therapy for Hormone Receptor–Positive/Human Epidermal Growth Factor Receptor 2–Negative Advanced Breast Cancer: Updated Analysis With Up to 5 Years of Follow-Up
Menée à partir des données de 3 essais cliniques portant sur des patientes atteintes d'un cancer du sein HR+ HER2- de stade avancé, cette étude évalue la toxicité à long terme du palbociclib en combinaison avec un traitement endocrinien (durée de suivi : 5 ans)
Background : Previous studies demonstrated the tolerability of palbociclib plus endocrine therapy (ET). This analysis evaluated safety based on more recent cutoff dates and a longer palbociclib treatment exposure. Patients and Methods : Data were pooled from 3 randomized studies of patients with hormone receptor–positive/human epidermal growth factor receptor 2–negative (HR+/HER2–) advanced breast cancer (ABC), including postmenopausal women who had not received prior systemic treatment for advanced disease (PALOMA‐1/‐2) and pre/postmenopausal women who had progressed on prior ET (PALOMA‐3). Results : Updated cutoff dates were December 21, 2017 (PALOMA‐1), May 31, 2017 (PALOMA‐2), and April 13, 2018 (PALOMA‐3). Total person‐years of treatment exposure were 1421.6 with palbociclib plus ET (n=872) and 528.4 with ET (n=471). Any‐grade neutropenia and infections were more frequent with palbociclib plus ET (82.1% and 59.2%, respectively) than ET (5.1% and 39.5%). The hazard ratios were 1.6 (P=0.0995) for grade 3/4 infections, 1.8 (P=0.4358) for grade 3/4 viral infections, 1.4 (P=0.0001) for infections, and 30.8 (P<0.0001) for neutropenia. Febrile neutropenia was reported in 1.4% of patients receiving palbociclib plus ET. Cumulative incidence of all‐grade hematologic adverse events in both arms peaked during the first year of treatment and plateaued over the 5 subsequent years. Interstitial lung disease was reported in 13 patients receiving palbociclib plus ET and 3 receiving ET. Conclusions : This 5‐year, long‐term analysis demonstrated that palbociclib plus ET has a consistent and stable safety profile and is a safe treatment for patients with HR+/HER2– ABC. Implications for Practice : Several treatments for patients with breast cancer are associated with long‐term or latent adverse events. This long‐term, 5‐year analysis demonstrated that palbociclib plus endocrine therapy has a consistent and stable safety profile without cumulative or delayed toxicities. These results further support palbociclib plus endocrine therapy as a safe and manageable treatment in clinical practice for patients with hormone receptor–positive/human epidermal growth factor receptor 2–negative advanced breast cancer.
The Oncologist 2021