Oncology; Radiology, Nuclear Medicine and Imaging; Pharmacology (medical)
Abstract :
[en] This nonrandomized, open-label, multi-cohort Phase 1b study (NCT02779751) investigated the safety and efficacy of abemaciclib plus pembrolizumab with/without anastrozole in patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (MBC) without prior CDK4 and 6 inhibitor exposure. Patients were divided into two cohorts: treatment naïve (cohort 1) and pretreated (cohort 2). Patients received abemaciclib plus pembrolizumab with (cohort 1) or without (cohort 2) anastrozole over 21-day cycles. The primary objective was safety, and secondary objectives included efficacy and pharmacokinetics (PK). Cohort 1/2 enrolled 26/28 patients, respectively. Neutropenia (30.8/28.6%), AST increase (34.6/17.9%), ALT increase (42.3/10.7%), and diarrhea (3.8/10.7%) were the most frequent grade ≥3 adverse events in cohort 1/2, respectively. A total of two deaths occurred, which investigators attributed to treatment-related adverse events (AEs), both in cohort 1. Higher rates of all grade and grade ≥3 interstitial lung disease (ILD)/pneumonitis were observed compared to previously reported with abemaciclib and pembrolizumab monotherapy. The PK profiles were consistent between cohorts and with previous monotherapy studies. In cohorts 1/2, the overall response rate and disease control rate were 23.1/28.6% and 84.6/82.1%, respectively. Median progression-free survival and overall survivals were 8.9 (95% CI: 3.9-11.1) and 26.3 months (95% CI: 20.0-31.0) for cohort 2; cohort 1 data are immature. Abemaciclib plus pembrolizumab demonstrated antitumor activity, but high rates of ILD/pneumonitis and severe transaminase elevations occurred with/without anastrozole compared to the previous reporting. Benefit/risk analysis does not support further evaluation of this combination in the treatment of HR+, HER2- MBC.
Disciplines :
Oncology
Author, co-author :
Rugo, Hope S ; University of California San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, USA. Hope.Rugo@ucsf.edu
Kabos, Peter; Divisions of Medical Oncology, Department of Medicine, University of Colorado, Anschutz Medical Campus, 12801 East 17th Avenue, Aurora, CO, 80045, USA
Beck, J Thad; Highlands Oncology Group, Fayetteville, AR, USA
Jerusalem, Guy ; Centre Hospitalier Universitaire de Liège - CHU > > Service d'oncologie médicale
Wildiers, Hans ; Department of General Medical Oncology, University Hospitals Leuven, Leuven, Belgium
Sevillano, Elena; Department of Medical Oncology, Centro Integral Oncologico Clara Campal, Madrid, Spain
Paz-Ares, Luis; Hospital Universitario 12 de Octubre, CNIO-H120 Lung Cancer Unit, Universidad Complutense and Ciberonc, Madrid, Spain
Chisamore, Michael J; Department of Clinical Research, Merck & Co., Inc., Rahway, NJ, USA
Chapman, Sonya C ; Eli Lilly and Company, Bracknell, UK
Hossain, Anwar M; Eli Lilly and Company, Indianapolis, IN, USA
Chen, Yanyun; Eli Lilly and Company, Indianapolis, IN, USA
Tolaney, Sara M ; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA
Language :
English
Title :
Abemaciclib in combination with pembrolizumab for HR+, HER2- metastatic breast cancer: Phase 1b study.
We thank the patients and families who participated in this study, caregivers, the study investigators, and their staff, and the JPCE (NCT02779751) clinical trial team. Pembrolizumab was provided by Merck & Co., Inc., Kenilworth, NJ, USA. We thank Anne Chain from the Department of Quantitative Pharmacology & Pharmacometrics—Immune/Oncology, Merck & Co., Inc., Kenilworth, NJ, USA for her contributions to this work, which included pembrolizumab PK and ADA analysis. This work and medical writing support was funded by Eli Lilly and Company.We thank the patients and families who participated in this study, caregivers, the study investigators, and their staff, and the JPCE (NCT02779751) clinical trial team. Pembrolizumab was provided by Merck & Co., Inc., Kenilworth, NJ, USA. We thank Anne Chain from the Department of Quantitative Pharmacology & Pharmacometrics—Immune/Oncology, Merck & Co., Inc., Kenilworth, NJ, USA for her contributions to this work, which included pembrolizumab PK and ADA analysis. This work and medical writing support was funded by Eli Lilly and Company.
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