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

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.

Keywords: Adverse event management; Dose modification; Dose reductions; Neutropenia; Palbociclib.

Conflict of interest statement

JE received consulting fees from Eli Lilly, Novartis, Pfizer, Roche, and Eisai; performed contracted research for Celgene; and received honoraria and travel support from Celgene, Eli Lilly, Novartis, Pfizer, Roche, and TEVA.

S-AI has advisory roles with AstraZeneca, Amgen, Hanmi Corp, Roche, Pfizer, and Novartis and has received grants from AstraZeneca and Pfizer.

NM reports honoraria from Chugai, AstraZeneca, Pfizer, and Takeda and research funds from Chugai, AstraZeneca, Kyowa-Kirin, MSD, Novartis, Pfizer, Eli Lilly, and Daiichi-Sankyo.

MCo reports a consulting or advisory role for Pfizer, OBI Pharma, AstraZeneca, Novartis, Pierre Fabre, Puma, and Celldex.

MCr reports personal fees from Pfizer, Novartis, and Merus.

HSR’s institution received research funding from Plexxikon, Macrogenics, OBI Pharma, Eisai, Pfizer, Novartis, Eli Lilly, Roche, and Merck.

RSF received consulting fees from Pfizer, Bayer, Novartis, Bristol-Myers Squibb, and Merck as well as other research funding from Pfizer and honoraria from Bayer, Pfizer, Bristol-Myers Squibb, Novartis, Eisai, and Eli Lilly.

PS, EB, and DRL are employees of and own stock in Pfizer.

JR declares that there are no competing interests.

Figures

Fig. 1

Timeline to first and second dose reduction by treatment cycle. Bars represent the percentage of patients who required dose reduction in each cycle. First dose reduction was from 125 to 100 mg. Second dose reduction was from 100 to 75 mg. C, cycle occurring after the dose reduction

Fig. 2

Incidence of neutropenia (neutropenia includes the following preferred terms: neutropenia and neutrophil count decreased) before and after palbociclib dose reduction from 125 to 100 mg. C, cycle occurring after the dose reduction

Fig. 3

Incidence of neutropenia (neutropenia includes the following preferred terms: neutropenia and neutrophil count decreased) before and after palbociclib dose reduction from 100 to 75 mg. C, cycle occurring after the dose reduction