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)

Springer Science and Business Media LLC - Tập 183 Số 2 - Trang 419-428 - 2020
Richard S. Finn1, Katalin Boér2, Igor Bondarenko3, Ravindranath Patel4, Tamás Pintér5, Marcus Schmidt6, Yaroslav Shparyk7, Anu Thummala8, Nataliia Voitko9, Eustratios Bananis10, Lynn McRoy10, Keith D. Wilner11, Xin Huang11, Sindy Kim11, Dennis J. Slamon1, Johannes Ettl12
1David Geffen School of Medicine, University of California Los Angeles, 2825 Santa Monica Blvd, Suite 200, Santa Monica, CA, USA
2Onkologia, Szent Margit Korhaz, Budapest, Hungary
3Dnipropetrovsk State Medical Academy, Dnipropetrovsk, Ukraine
4Comprehensive Blood and Cancer Center, Bakersfield, CA, USA
5Petz Aladar Megyei Oktato Korhaz, Gyor, Hungary
6Department of Obstetrics and Gynecology, University Medical Center Mainz, Mainz, Germany
7Lviv State Oncologic Regional Treatment and Diagnostic Center, Lviv, Ukraine
8Comprehensive Cancer Centers of Nevada, Las Vegas, NV, USA
9Kyiv City Clinical Oncology Center, Kyiv, Ukraine
10Pfizer Inc., New York, NY, USA
11Pfizer Inc, San Diego, CA, USA
12Department of Obstetrics and Gynecology, Klinikum Rechts Der Isar, Technische Universität München, München, Germany

Tóm tắt

AbstractPurposePalbociclib 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)

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