Hematologic adverse events following palbociclib dose reduction in patients with hormone receptor–positive/human epidermal growth factor receptor 2–negative advanced breast cancer: pooled analysis from randomized phase 2 and 3 studies

Breast Cancer Research

Richard S. Finn¹  Johannes Ettl²  Marco Colleoni³  Jungsil Ro⁴  Norikazu Masuda⁵  Dongrui R. Lu⁶  Patrick Schnell⁷  Eustratios Bananis⁷  Massimo Cristofanilli⁸  Seock-Ah Im⁹  Hope S. Rugo^1,10 

[1] David Geffen School of Medicine at University of California Los Angeles;Department of Obstetrics and Gynecology, Klinikum rechts der Isar, Technische Universität München;IEO, European Institute of Oncology, IRCCS;National Cancer Center;National Hospital Organization Osaka National Hospital;Pfizer Inc;Pfizer Oncology;Robert H. Lurie Cancer Center of Northwestern University, Feinberg School of Medicine;Seoul National University Hospital Cancer Research Institute, Seoul National University College of Medicine;University of California San Francisco Helen Diller Family Comprehensive Cancer Center;

关键词: Palbociclib;    Adverse event management;    Neutropenia;    Dose reductions;    Dose modification;   

DOI  :  10.1186/s13058-020-01263-0

来源: DOAJ

【 摘 要 】

Abstract Background Palbociclib improves outcomes for women with hormone receptor–positive/human epidermal growth factor receptor 2–negative advanced breast cancer (HR+/HER2− ABC). Dose reductions are recommended for the management of hematologic toxicities. A previous pooled analysis from the PALOMA clinical trials showed that 36.9% of patients required dose reduction, predominantly during the first 6 months of treatment and with decreasing frequency during subsequent 28-day treatment cycles (C). Previous data have shown that palbociclib dose reductions do not affect efficacy. This pooled, post hoc analysis evaluated the frequency of hematologic adverse events (AEs) before and after palbociclib dose reduction in PALOMA-1, PALOMA-2, and PALOMA-3. Methods This analysis evaluated the frequency of hematologic AEs 30 days before dose reduction and during each subsequent treatment from C1 to C6 among patients who required palbociclib dose reduction. Data were pooled from 3 randomized studies. PALOMA-1 was a phase 2, open-label study of postmenopausal patients untreated for ABC receiving palbociclib plus letrozole or letrozole alone. PALOMA-2 was a phase 3, double-blind study of postmenopausal patients untreated for ABC receiving palbociclib plus letrozole or placebo plus letrozole. PALOMA-3 was a phase 3, double-blind study of pre/perimenopausal or postmenopausal patients, whose disease progressed on prior endocrine therapy, receiving palbociclib plus fulvestrant or placebo plus fulvestrant. Results A total of 311 (35.5%) patients with HR+/HER2− ABC required a palbociclib dose reduction (93.6% due to AEs) from 125 to 100 mg. Mean patient age was 59.9 years, and 46.9% of patients had visceral disease. Median time to dose reduction was 70 days. The majority of dose reductions occurred within 3 months of starting palbociclib treatment. Incidences of all-grade and grades 3/4 hematologic AEs were lower following dose reduction. Conclusions A decrease in frequency and severity of hematologic AEs, including febrile neutropenia, following palbociclib dose reduction was observed, supporting the recommended use of dose reduction in AE management. Trial registration These studies were sponsored by Pfizer. ClinicalTrials.gov: NCT00721409 ; registration date July 24, 2008. ClinicalTrials.gov: NCT01740427 ; registration date December 4, 2012. ClinicalTrials.gov: NCT01942135 ; registration date September 13, 2013.

【 授权许可】

Unknown