Phase I/II trial of palbociclib, pembrolizumab and letrozole in patients with hormone receptor-positive metastatic breast cancer.

Autor: Yuan Y; Department of Medical Oncology & Therapeutics Research, City of Hope Comprehensive Cancer Center, Beckman Research Institute, Duarte, CA, USA. Electronic address: yuyuan@coh.org., Lee JS; Department of Medical Oncology & Therapeutics Research, City of Hope Comprehensive Cancer Center, Beckman Research Institute, Duarte, CA, USA., Yost SE; Department of Medical Oncology & Therapeutics Research, City of Hope Comprehensive Cancer Center, Beckman Research Institute, Duarte, CA, USA., Frankel PH; Department of Biostatistics, City of Hope Comprehensive Cancer Center, Beckman Research Institute, Duarte, CA, USA., Ruel C; Department of Biostatistics, City of Hope Comprehensive Cancer Center, Beckman Research Institute, Duarte, CA, USA., Egelston CA; Department of Immune-Oncology, City of Hope Comprehensive Cancer Center, Beckman Research Institute, Duarte, CA, USA., Guo W; Department of Immune-Oncology, City of Hope Comprehensive Cancer Center, Beckman Research Institute, Duarte, CA, USA., Padam S; Department of Medical Oncology & Therapeutics Research, City of Hope Comprehensive Cancer Center, Beckman Research Institute, Duarte, CA, USA., Tang A; Department of Medical Oncology & Therapeutics Research, City of Hope Comprehensive Cancer Center, Beckman Research Institute, Duarte, CA, USA., Martinez N; Department of Medical Oncology & Therapeutics Research, City of Hope Comprehensive Cancer Center, Beckman Research Institute, Duarte, CA, USA., Schmolze D; Department of Pathology, City of Hope Comprehensive Cancer Center, Beckman Research Institute, Duarte, CA, USA., Presant C; Department of Medical Oncology & Therapeutics Research, City of Hope Comprehensive Cancer Center, Beckman Research Institute, Duarte, CA, USA., Ebrahimi B; Department of Medical Oncology & Therapeutics Research, City of Hope Comprehensive Cancer Center, Beckman Research Institute, Duarte, CA, USA., Yeon C; Department of Medical Oncology & Therapeutics Research, City of Hope Comprehensive Cancer Center, Beckman Research Institute, Duarte, CA, USA., Sedrak M; Department of Medical Oncology & Therapeutics Research, City of Hope Comprehensive Cancer Center, Beckman Research Institute, Duarte, CA, USA., Patel N; Department of Medical Oncology & Therapeutics Research, City of Hope Comprehensive Cancer Center, Beckman Research Institute, Duarte, CA, USA., Portnow J; Department of Medical Oncology & Therapeutics Research, City of Hope Comprehensive Cancer Center, Beckman Research Institute, Duarte, CA, USA., Lee P; Department of Immune-Oncology, City of Hope Comprehensive Cancer Center, Beckman Research Institute, Duarte, CA, USA., Mortimer J; Department of Medical Oncology & Therapeutics Research, City of Hope Comprehensive Cancer Center, Beckman Research Institute, Duarte, CA, USA.
Jazyk: angličtina
Zdroj: European journal of cancer (Oxford, England : 1990) [Eur J Cancer] 2021 Sep; Vol. 154, pp. 11-20. Date of Electronic Publication: 2021 Jul 01.
DOI: 10.1016/j.ejca.2021.05.035
Abstrakt: Background: CDK4/6 inhibitors modulate immune response in breast cancer. This phase I/II trial was designed to test the safety and efficacy of palbociclib, pembrolizumab and letrozole in women with hormone receptor positive (HR + ) human epidermal growth factor receptor 2 negative (HER2 - ) metastatic breast cancer (MBC).
Patients and Methods: Women with stage IV HR + HER2 - MBC were enrolled and treated with palbociclib, pembrolizumab and letrozole. Primary end-points were safety, tolerability and efficacy.
Results: Between November 2016 and July 2020, 23 patients were enrolled with 20 evaluable for response, including 4 patients in cohort 1 and 16 patients in cohort 2. Cohort 1 median age was 48 years (33-70) and cohort 2 median age was 55 (37-75). Cohort 1 closed early due to limited accrual. Grade III-IV adverse events were neutropenia (83%), leucopaenia (65%), thrombocytopenia (17%) and elevated liver enzymes (17%). In cohort 1, 50% achieved a partial response (PR) and 50% had stable disease (SD). In cohort 2, 31% achieved complete response (CR), 25% had PR and 31% had SD by Response Evaluation Criteria in Solid Tumours version 1.1. Median progression-free survival was 25.2 months (95% confidence interval [CI] 5.3, not reached) and median overall survival was 36.9 months (95% CI 36.9, not reached) in cohort 2 with a median follow-up of 24.8 months (95% CI 17.1, not reached). A correlative immune biomarker analysis was published separately.
Conclusion: The combination of palbociclib, pembrolizumab and letrozole is well tolerated, and a complete response rate of 31% was identified in HR + MBC patients who received this combination as front-line therapy. Confirmatory trials are required to better understand the immune-priming effects of CDK4/6 inhibitors.
Competing Interests: Conflict of interest statement Dr. Yuan has contracted research sponsored by Merck, Eisai, Novartis, Puma, Genentech, Celgene, and Pfizer; is a consultant for Puma, Pfizer, and Immunomedics; and is on the Speakers Bureau for Eisai, Genentech, AstraZeneca, Daiichi Sankyo, Pfizer, Merck, and Immunomedics. The other authors declare they have no competing interests.
(Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)
Databáze: MEDLINE
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