Overall survival results from the randomized phase 2 study of palbociclib in combination with letrozole versus letrozole alone for first-line treatment of ER+/HER2- advanced breast cancer (PALOMA-1, TRIO-18)

Abstract

Purpose: Palbociclib is a cyclin-dependent kinase 4/6 (CDK4/6) inhibitor, approved in combination with endocrine therapy for the treatment of women and men with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer (HR+/HER2- ABC). In the phase 2, open-label, PALOMA-1 trial, palbociclib plus letrozole significantly prolonged progression-free survival (PFS) versus letrozole alone (hazard ratio, 0.488; 95% CI 0.319‒0.748; P = 0.0004; median PFS, 20.2 vs 10.2 months, respectively) in postmenopausal women with estrogen receptor-positive (ER+)/HER2- ABC. Here, we present the final overall survival (OS) and updated safety results.

Methods: Postmenopausal women with ER+/HER2- ABC were randomized 1:1 to receive either palbociclib (125 mg/day, 3/1 schedule) plus letrozole (2.5 mg/day, continuous) or letrozole alone (2.5 mg/day, continuous). The primary endpoint was investigator-assessed PFS; secondary endpoints included OS and safety.

Results: A total of 165 patients were randomized. At the data cutoff date of December 30, 2016 (median duration of follow-up, 64.7 months), the stratified hazard ratio for OS was 0.897 (95% CI 0.623-1.294; P = 0.281); median OS in the palbociclib plus letrozole and letrozole alone arms was 37.5 and 34.5 months, respectively. The median time from randomization to first subsequent chemotherapy use was longer with palbociclib plus letrozole than letrozole alone (26.7 and 17.7 months, respectively). The most frequently reported adverse event in the palbociclib plus letrozole arm was neutropenia (any grade, 75%; grade 3 or 4, 59%).

Conclusions: Palbociclib plus letrozole treatment led to a numerical but not statistically significant improvement in median OS. Pfizer Inc (NCT00721409).

Keywords: Advanced breast cancer; ER+/HER2−; Letrozole; Overall survival; Palbociclib.

Fig. 1

Overall survival in the ITT population and by subgroup. a Kaplan–Meier curve of OS in the ITT population. b Forest plot of OS by subgroup. ECOG Eastern Cooperative Oncology Group, ITT intention-to-treat, LET letrozole, NE not estimable, OS overall survival, PAL palbociclib, PBO placebo

Fig. 2

Kaplan–Meier estimated time to first use of chemotherapy postprogression. LET letrozole, PAL palbociclib

Fig. 3

Cumulative incidence of all-causality AEs > 15% during the first 5 years of treatment with palbociclib in the as-treated set. a Hematologic AEs. b Nonhematologic AEs. AE adverse event. *Grouped terms were as follows: neutropenia included the preferred terms neutropenia or neutrophil count decreased; anemia included the preferred terms anemia, hematocrit decreased, or hemoglobin decreased; leukopenia included the preferred terms leukopenia or white blood cell count decreased; infections included any preferred term that is part of the System Organ Class infections and infestations; and stomatitis included the preferred terms aphthous stomatitis, cheilitis, glossitis, glossodynia, mouth ulceration, mucosal inflammation, oral pain, oropharyngeal discomfort, oropharyngeal pain, or stomatitis. †Patient percentage was calculated based on an n = 83 denominator