Palbociclib in combination with fulvestrant in women with hormone receptor-positive/HER2-negative advanced metastatic breast cancer: Detailed safety analysis from a multicenter, randomized, placebo-controlled, phase III study (PALOMA-3)

Sunil Verma, Cynthia Huang Bartlett, Patrick Schnell, Angela M. DeMichele, Sherene Loi, Jungsil Ro, Marco Colleoni, Hiroji Iwata, Nadia Harbeck, Massimo Cristofanilli, Ke Zhang, Alexandra Thiele, Nicholas C. Turner, Hope S. Rugo

Research output: Contribution to journalArticlepeer-review

Abstract

Background. Palbociclib enhances endocrine therapy and improves clinical outcomes in hormone receptor (HR)- positive/human epidermal growth factor receptor 2 (HER2)- negative metastatic breast cancer (MBC). Because this is anew target, it is clinically important to understand palbociclib’s safety profile to effectively manage toxicity and optimize clinical benefit. Materials and Methods. Patients with endocrine-resistant, HR-positive/HER2-negative MBC (n 5 521) were randomly assigned 2:1 to receive fulvestrant (500 mg intramuscular injection) with or without goserelin with oral palbociclib (125 mg daily; 3 weeks on/1 week off) or placebo. Safety assessments at baseline and day 1 of each cycle included blood counts on day 15 for the first 2 cycles. Hematologic toxicity was assessed by using laboratory data. Results. A total of 517 patients were treated (palbociclib, n 5 345; placebo, n 5 172); median follow-up was 8.9 months. With palbociclib, neutropenia was the most common grade 3 (55%) and 4 (10%) adverse event; median times to onset and duration of grade $3 episodes were 16 and 7 days, respectively. Asian ethnicity and below-median neutrophil counts at baseline were significantly associated with an increased chance of developing grade 3–4 neutropenia with palbociclib. Dose modifications for grade 3–4 neutropenia had no adverse effect on progression-free survival. In the palbociclib arm, febrile neutropenia occurred in 3 (,1%) patients. The percentage of grade 1–2 infections was higher than in the placebo arm. Grade 1 stomatitis occurred in 8% of patients. Conclusion. Palbociclib plus fulvestrant treatment was welltolerated, and the primary toxicity of asymptomatic neutropenia was effectively managed by dose modification without apparent loss of efficacy. This study appears at ClinicalTrials. gov, NCT01942135.

Original languageEnglish
Pages (from-to)1165-1175
Number of pages11
JournalOncologist
Volume21
Issue number10
DOIs
Publication statusPublished - Oct 1 2016

Keywords

  • Cyclin-dependent kinase 4
  • Cyclin-dependent kinase 6
  • Neutropenia
  • Palbociclib

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Palbociclib in combination with fulvestrant in women with hormone receptor-positive/HER2-negative advanced metastatic breast cancer: Detailed safety analysis from a multicenter, randomized, placebo-controlled, phase III study (PALOMA-3)'. Together they form a unique fingerprint.

Cite this