Journal Article

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)

Bananis, Eustratios, Pinter, Tamas, Schmidt, Marcus, McRoy, Lynn, Kim, Sindy, Boer, Katalin, Huang, Xin, Slamon, Dennis J., Finn, Richard S., Thummala, Anu, Patel, Ravindranath, Voitko, Nataliia, Bondarenko, Igor, Ettl, Johannes, Shparyk, Yaroslav V., Wilner, Keith

2020

Overview

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)

• Publisher: Springer US,Springer,Springer Nature B.V
• Subject: Adult / Aged / Aged, 80 and over / Antineoplastic Combined Chemotherapy Protocols - therapeutic use / Breast cancer / Breast Neoplasms - drug therapy / Breast Neoplasms - metabolism / Breast Neoplasms - mortality / Breast Neoplasms - pathology / Cancer research / Cancer therapies / Care and treatment / Chemotherapy / Clinical Trial / Cyclin-dependent kinase 4 / Cyclin-dependent kinases / Development and progression / Endocrine therapy / Epidermal growth factor / ErbB-2 protein / Estrogen Receptor alpha - metabolism / Estrogen receptors / Female / Fulvestrant / Humans / Kinases / Letrozole - administration & dosage / Medicine / Medicine & Public Health / Middle Aged / Neutropenia / Oncology / Patient outcomes / Piperazines - administration & dosage / Post-menopause / Postmenopausal women / Postmenopause / Product development / Pyridines - administration & dosage / Receptor, ErbB-2 - metabolism / Statistical analysis / Survival / Survival Rate / Treatment Outcome / Women