Abstract
PurposeIn the initial PALOMA-2 (NCT01740427) analysis with median follow-up of 23 months, palbociclib plus letrozole significantly prolonged progression-free survival (PFS) in women with estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2−) advanced breast cancer (ABC) [hazard ratio (HR) 0.58; P < 0.001]. Herein, we report results overall and by subgroups with extended follow-up.MethodsIn this double-blind, phase 3 study, post-menopausal women with ER+/HER2− ABC who had not received prior systemic therapy for their advanced disease were randomized 2:1 to palbociclib-letrozole or placebo-letrozole. Endpoints include investigator-assessed PFS (primary), safety, and patient-reported outcomes (PROs).ResultsAfter a median follow-up of approximately 38 months, median PFS was 27.6 months for palbociclib–letrozole (n = 444) and 14.5 months for placebo-letrozole (n = 222) (HR 0.563; 1-sided P < 0.0001). All subgroups benefited from palbociclib treatment. The improvement of PFS with palbociclib-letrozole was maintained in the next 2 subsequent lines of therapy and delayed the use of chemotherapy (40.4 vs. 29.9 months for palbociclib–letrozole vs. placebo-letrozole). Safety data were consistent with the known profile. Patients’ quality of life was maintained.ConclusionsWith approximately 15 months of additional follow-up, palbociclib plus letrozole continued to demonstrate improved PFS compared with placebo plus letrozole in the overall population and across all patient subgroups, while the safety profile remained favorable and quality of life was maintained. These data confirm that palbociclib-letrozole should be considered the standard of care for first-line therapy in patients with ER+/HER2− ABC, including those with low disease burden or long disease-free interval. Sponsored by Pfizer; ClinicalTrials.gov: NCT01740427.
Highlights
Endocrine therapy has been the primary first-line treatment for hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2−) advanced breast cancer (ABC) [1,2,3]
Investigator-assessed progression-free survival (PFS) was significantly longer with palbociclib-letrozole versus placebo-letrozole in the ITT population, with a median of 27.6 months versus 14.5 months (12.3‒17.1), respectively [HR, 0.563; P < 0.0001] (Fig. 1a)
This improvement in PFS with palbociclib was supported by the results of the updated blinded independent central review: median PFS 35.7 months versus 19.5 months (16.6–26.6), respectively [HR, 0.611; P < 0.0001]
Summary
Endocrine therapy has been the primary first-line treatment for hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2−) advanced breast cancer (ABC) [1,2,3]. Guidelines have expanded to include the addition of a cyclin-dependent kinase 4/6 (CDK4/6) inhibitor in combination with endocrine therapy for the treatment of pre-menopausal/post-menopausal women with HR+/HER2‒ ABC [1,2,3]. The primary analysis was conducted after a median 23 months of follow-up (data cut-off: February 26, 2016), with the investigators and patients remaining blinded to treatment assignments. Because patients with HR+/ HER2− ABC receiving first-line therapy have diverse clinical and molecular presentations (e.g., de novo versus recurrent disease, visceral versus bone-only), response to endocrinebased therapy could be prolonged in a particular subgroup. It is important to analyze the long-term efficacy of treatment with extended follow-up in different patient subgroups
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
