PMID- 36335120 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20221108 IS - 2374-4677 (Print) IS - 2374-4677 (Electronic) IS - 2374-4677 (Linking) VI - 8 IP - 1 DP - 2022 Nov 5 TI - Abemaciclib in combination with pembrolizumab for HR+, HER2- metastatic breast cancer: Phase 1b study. PG - 118 LID - 10.1038/s41523-022-00482-2 [doi] LID - 118 AB - 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 naive (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. CI - (c) 2022. The Author(s). FAU - Rugo, Hope S AU - Rugo HS AUID- ORCID: 0000-0001-6710-4814 AD - University of California San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, USA. Hope.Rugo@ucsf.edu. FAU - Kabos, Peter AU - Kabos P AD - Divisions of Medical Oncology, Department of Medicine, University of Colorado, Anschutz Medical Campus, 12801 East 17th Avenue, Aurora, CO, 80045, USA. FAU - Beck, J Thad AU - Beck JT AD - Highlands Oncology Group, Fayetteville, AR, USA. FAU - Jerusalem, Guy AU - Jerusalem G AD - Laboratory of Medical Oncology, University of Liege, Liege, Belgium. AD - Department of Medical Oncology, CHU Sart-Tilman Liege, Liege, Belgium. FAU - Wildiers, Hans AU - Wildiers H AUID- ORCID: 0000-0001-8990-7837 AD - Department of General Medical Oncology, University Hospitals Leuven, Leuven, Belgium. FAU - Sevillano, Elena AU - Sevillano E AD - Department of Medical Oncology, Centro Integral Oncologico Clara Campal, Madrid, Spain. FAU - Paz-Ares, Luis AU - Paz-Ares L AD - Hospital Universitario 12 de Octubre, CNIO-H120 Lung Cancer Unit, Universidad Complutense and Ciberonc, Madrid, Spain. FAU - Chisamore, Michael J AU - Chisamore MJ AD - Department of Clinical Research, Merck & Co., Inc., Rahway, NJ, USA. FAU - Chapman, Sonya C AU - Chapman SC AUID- ORCID: 0000-0002-6453-2749 AD - Eli Lilly and Company, Bracknell, UK. FAU - Hossain, Anwar M AU - Hossain AM AD - Eli Lilly and Company, Indianapolis, IN, USA. FAU - Chen, Yanyun AU - Chen Y AD - Eli Lilly and Company, Indianapolis, IN, USA. FAU - Tolaney, Sara M AU - Tolaney SM AUID- ORCID: 0000-0002-5940-8671 AD - Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. LA - eng PT - Journal Article DEP - 20221105 PL - United States TA - NPJ Breast Cancer JT - NPJ breast cancer JID - 101674891 PMC - PMC9637121 COIS- The authors declare no competing nonfinancial interests but the following competing financial interests: H.S.R. reports grants (institutional) from Eli Lilly and Company during the conduct of the study; grants (institutional) from Pfizer, Merck, Novartis, Eli Lilly and Company, Genentech, OBI, Odonate, Daiichi, Eisai, Seattle Genetics, Macrogenics, Sermonixs, Immunomedics and AstraZeneca; educational travel support from Daiichi, Mylan, Pfizer, Merck, Novartis, AstraZeneca, Macrogenics, and honoraria from Puma, Mylan and Samsung outside the submitted work. P.K. reports grants (institutional) from Eli Lilly and Company during the conduct of this study; grants (institutional) from Pfizer, AstraZeneca, Genentech, Radius Health; participated in an advisory board meeting with Eli Lilly and Company. J.T.B. reports grants from Eli Lilly and Company (institutional) during the conduct of the study. G.J. reports personal fees and nonfinancial support from Eli Lilly and Company during the conduct of the study; grants, personal fees and nonfinancial support from Novartis, Roche, and Pfizer; personal fees and nonfinancial support from Lilly, Amgen, BMS and Astra-Zeneca; personal fees from Daiichi-Sankyo and Abbvie; nonfinancial support from Medimmune and MerckKGaA outside the submitted work. H.W. reports grants from Roche; financial support (institutional) for advisory boards and lecture fees from Immutep Pty, MSD, Astrazenca Ireland, Daiichi, AbbVie, Eli Lilly and Company, PSI CRO AG, KCE, EISAI, Astrazeneca, Roche, Lilly, Congres care, Pfizer, ARIEZ, Sirtex, TRM Oncology, ORION Corporation, The Planning Shop, Novartis, Biocartes and Puma Biotech. E.S. reports grants from Roche, MSD and BMS; honoraria from Roche, Janssen, MSD and BMS; travel/meeting expenses Roche and Pfizer; consulting fees from Roche; participation on a data safety monitoring board/advisory board for Roche; leadership/fiduciary role in other board for Roche. L.P.-A. reports fees for scientific advice from MSD, Roche, Eli Lilly and Company, Merck, Novartis, Angem, Takeda, Blueprint, Bayer, Pharmamar, and Pfizer; grants and fees for scientific advice from BMS and Astra Zeneca; and is an external board member for Genomica and a founder and board member for Altum sequencing, outside the submitted work. M.J.C. is an employee and shareholder of Merck & Co., Inc. S.C.C., A.M.H., and Y.C. are employees and shareholders of Eli Lilly and Company. S.M.T. reports research funding from Eli Lilly and Company during the conduct of the study; reports grants (institutional) from AstraZeneca, Eli Lilly and Company, Merck, Nektar, Novartis, Pfizer, Genentech/Roche, Immunomedics/Gilead, Exelixis, BMS, Eisai, Nanostring, Cyclacel, Sanofi, Odonate and SeaGen; honoraria from AstraZeneca, Eli Lilly, Merck, Nektar, Novartis, Pfizer, Genentech/Roche, Immunomedics/Gilead and BMS; consulting fees from Eisai, Nanostring, Sanofi, Odonate, SeaGen, Daiichi-Sankyo, Athenex, OncoPep, Kyowa Kirin Pharma, CytomX, Certara, Mersana Therapeutics, Ellipses Pharma, 4D Pharma, OncoSec, G1 Therapeutics, Silverback Therapeutics, Celldex Therapeutics and OncXerna; participation on a data safety monitoring board/advisory board/steering committee for Odonate, BMS, CytomX, Eli Lilly and Company, Immunomedics, SeaGen, AstraZeneca, Nektar and Gilead/Immunomedics. EDAT- 2022/11/06 06:00 MHDA- 2022/11/06 06:01 PMCR- 2022/11/05 CRDT- 2022/11/06 00:24 PHST- 2022/03/03 00:00 [received] PHST- 2022/09/26 00:00 [accepted] PHST- 2022/11/06 00:24 [entrez] PHST- 2022/11/06 06:00 [pubmed] PHST- 2022/11/06 06:01 [medline] PHST- 2022/11/05 00:00 [pmc-release] AID - 10.1038/s41523-022-00482-2 [pii] AID - 482 [pii] AID - 10.1038/s41523-022-00482-2 [doi] PST - epublish SO - NPJ Breast Cancer. 2022 Nov 5;8(1):118. doi: 10.1038/s41523-022-00482-2.