Palbociclib and Letrozole in Advanced Breast Cancer
Top Cited Papers
- 17 November 2016
- journal article
- research article
- Published by Massachusetts Medical Society in The New England Journal of Medicine
- Vol. 375 (20), 1925-1936
- https://doi.org/10.1056/nejmoa1607303
Abstract
A phase 2 study showed that progression-free survival was longer with palbociclib plus letrozole than with letrozole alone in the initial treatment of postmenopausal women with estrogen-receptor (ER)–positive, human epidermal growth factor receptor 2 (HER2)–negative advanced breast cancer. We performed a phase 3 study that was designed to confirm and expand the efficacy and safety data for palbociclib plus letrozole for this indication. In this double-blind study, we randomly assigned, in a 2:1 ratio, 666 postmenopausal women with ER-positive, HER2-negative breast cancer, who had not had prior treatment for advanced disease, to receive palbociclib plus letrozole or placebo plus letrozole. The primary end point was progression-free survival, as assessed by the investigators; secondary end points were overall survival, objective response, clinical benefit response, patient-reported outcomes, pharmacokinetic effects, and safety. The median progression-free survival was 24.8 months (95% confidence interval [CI], 22.1 to not estimable) in the palbociclib–letrozole group, as compared with 14.5 months (95% CI, 12.9 to 17.1) in the placebo–letrozole group (hazard ratio for disease progression or death, 0.58; 95% CI, 0.46 to 0.72; P<0.001). The most common grade 3 or 4 adverse events were neutropenia (occurring in 66.4% of the patients in the palbociclib–letrozole group vs. 1.4% in the placebo–letrozole group), leukopenia (24.8% vs. 0%), anemia (5.4% vs. 1.8%), and fatigue (1.8% vs. 0.5%). Febrile neutropenia was reported in 1.8% of patients in the palbociclib–letrozole group and in none of the patients in the placebo–letrozole group. Permanent discontinuation of any study treatment as a result of adverse events occurred in 43 patients (9.7%) in the palbociclib–letrozole group and in 13 patients (5.9%) in the placebo–letrozole group. Among patients with previously untreated ER-positive, HER2-negative advanced breast cancer, palbociclib combined with letrozole resulted in significantly longer progression-free survival than that with letrozole alone, although the rates of myelotoxic effects were higher with palbociclib–letrozole. (Funded by Pfizer; PALOMA-2 ClinicalTrials.gov number, NCT01740427.)Keywords
This publication has 12 references indexed in Scilit:
- Phase III Trial Evaluating Letrozole As First-Line Endocrine Therapy With or Without Bevacizumab for the Treatment of Postmenopausal Women With Hormone Receptor–Positive Advanced-Stage Breast Cancer: CALGB 40503 (Alliance)Journal of Clinical Oncology, 2016
- Fulvestrant plus palbociclib versus fulvestrant plus placebo for treatment of hormone-receptor-positive, HER2-negative metastatic breast cancer that progressed on previous endocrine therapy (PALOMA-3): final analysis of the multicentre, double-blind, phase 3 randomised controlled trialThe Lancet Oncology, 2016
- Targeting the cyclin-dependent kinases (CDK) 4/6 in estrogen receptor-positive breast cancersBreast Cancer Research, 2016
- FDA Approval: Palbociclib for the Treatment of Postmenopausal Patients with Estrogen Receptor–Positive, HER2-Negative Metastatic Breast CancerClinical Cancer Research, 2015
- Enhancing Endocrine Therapy for Hormone Receptor–Positive Advanced Breast Cancer: Cotargeting Signaling PathwaysJNCI Journal of the National Cancer Institute, 2015
- Phase III Trial Evaluating the Addition of Bevacizumab to Endocrine Therapy As First-Line Treatment for Advanced Breast Cancer: The Letrozole/Fulvestrant and Avastin (LEA) StudyJournal of Clinical Oncology, 2015
- The cyclin-dependent kinase 4/6 inhibitor palbociclib in combination with letrozole versus letrozole alone as first-line treatment of oestrogen receptor-positive, HER2-negative, advanced breast cancer (PALOMA-1/TRIO-18): a randomised phase 2 studyThe Lancet Oncology, 2015
- Changing Concepts of Hormone Receptor–Positive Advanced Breast Cancer TherapyClinical Breast Cancer, 2012
- PD 0332991, a selective cyclin D kinase 4/6 inhibitor, preferentially inhibits proliferation of luminal estrogen receptor-positive human breast cancer cell lines in vitroBreast Cancer Research, 2009
- New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1)European Journal of Cancer, 2009