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: An updated analysis

Background Palbociclib (PAL) in combination with endocrine therapy (ET) was shown to be tolerable in a previous pooled analysis of the 3 PALOMA clinical trials. This new pooled, post hoc analysis examines the safety profile of PAL + ET using data from more recent data cutoff dates with longer drug exposure. Methods Data were pooled from 3 randomized phase 2 and 3 studies of patients with hormone receptor-positive/human epidermal growth factor receptor 2–negative advanced breast cancer (HR+/HER2- ABC). Postmenopausal first-line patients were randomized to receive letrozole (2.5 mg/d, continuously) +/- PAL (125 mg/d, 3/1 schedule) in PALOMA-1 or letrozole (2.5 mg/d, continuously) + PAL (125 mg/d, 3/1 schedule)/placebo in PALOMA-2. In PALOMA-3, pre/peri- and postmenopausal patients with prior endocrine resistance received intramuscular fulvestrant (500 mg every 14 days for the first 3 injections, then every 28 days) + PAL (125 mg/d, 3/1 schedule)/placebo. The cumulative rates of adverse events (AEs) were assessed over time. Results Updated data cutoff dates used for this analysis were December 21, 2017 (PALOMA-1), May 31, 2017 (PALOMA-2), and April 13, 2018 (PALOMA-3). The total number of person-years of exposure was 1950 (1422 PAL + ET, 528 ET). In the ET arm (n=471), 20.2% of patients were treated for ≥24 months and 10.2% were treated for ≥36 months. In the PAL + ET arm (n=872), 36% of patients were treated for ≥24 months and 22.4% for ≥36 months. The majority of patients treated for ≥24 and ≥36 months in the PAL + ET arm were from PALOMA-2. As expected, neutropenia and infections (any grade) were more frequent with PAL + ET (82.1% and 59.2%, respectively) than in the ET arm (5.1% and 39.5%). Febrile neutropenia was reported in 1.4% of patients in the PAL + ET arm. The incidence of hematologic AEs in the PAL + ET arm peaked during the first year of treatment and then plateaued over the subsequent 5 years. Serious AEs were reported in 22.8% of patients in the PAL + ET arm and 15.5% in the ET arm. Selected cumulative grade 3/4 event rates through 5 years were neutropenia (68.3% in PAL + ET; 0.8% in ET), leukopenia (29.9%; 0.2%), infections (6.4%; 2.8%), anemia (5.3%; 2.1%), fatigue (2.9%; 1.3%), alanine aminotransferase increased (2.2%; 0.2%), aspartate aminotransferase increased (2.9%; 1.3%), diarrhea (1%; 1.1%), nausea (0.6%; 1.3%), vomiting (0.7%; 1.1%), and QTc prolongation (0.3%; 0.2%). After adjusting for treatment exposure, incidence rates of venous thromboembolism and pulmonary embolism were 0.0225 (PAL + ET) and 0.0246 (ET) per person-year and 0.0127 (PAL + ET) and 0.0132 (ET) per person-year, respectively. Conclusion This 5-year, long-term safety analysis of PAL + ET showed a consistent profile with no new safety signals, and no cumulative/delayed toxicities. PAL + ET remains a safe and manageable treatment for patients with HR+/HER2- ABC. Pfizer (NCT00721409, NCT01740427, NCT01942135) Citation Format: Richard S Finn, Hope S Rugo, Karen Gelmon, Massimo Cristofanilli, Marco Colleoni, Sherene Loi, Patrick Schnell, Dongrui R Lu, Kathy P Theall, Ave Mori, Eric Gauthier, Eustratios Bananis, Nicholas C Turner, Veronique Dieras. 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: An updated analysis [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-19-16.