Abstract
PurposePalbociclib 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.MethodsPostmenopausal 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.ResultsA 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%).ConclusionsPalbociclib plus letrozole treatment led to a numerical but not statistically significant improvement in median OS.Pfizer Inc (NCT00721409)
Highlights
Breast cancer is the most common type of cancer in women worldwide [1]; approximately 70% of breast cancers are hormone receptor–positive/human epidermal growth factor receptor 2–negative (HR+/HER2−) [2]
84 and 81 patients were randomized into the palbociclib plus letrozole arm and letrozole alone arm, respectively
As of the data cutoff date (December 30, 2016), 80 patients in the palbociclib plus letrozole arm and 79 patients in the letrozole arm had permanently discontinued from the study
Summary
Breast cancer is the most common type of cancer in women worldwide [1]; approximately 70% of breast cancers are hormone receptor–positive/human epidermal growth factor receptor 2–negative (HR+/HER2−) [2]. Single-agent endocrine therapy (ET; including antiestrogens and aromatase inhibitors [AIs]) had long been the mainstay of therapy for first-line treatment in postmenopausal women, with a better safety profile and quality of life compared with standard chemotherapy [4]. Preclinical studies revealed that palbociclib in combination with ET preferentially and synergistically inhibited the cell cycle in human estrogen receptor–positive (ER+) breast cancer cell lines [7]. Based on these preclinical data, the phase 2 PALOMA-1 clinical trial was initiated to investigate the efficacy and safety of palbociclib plus ET as first-line treatment for postmenopausal women with ER+/HER2− ABC [8]. The results from this study led to the accelerated US Food and Drug Administration approval of palbociclib in combination with letrozole for the treatment of ER+/HER2− ABC in February 2015
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