Pembrolizumab plus eribulin in hormone-receptor-positive, HER2-negative, locally recurrent or metastatic breast cancer (KELLY): An open-label, multicentre, single-arm, phase Ⅱ trial
- PMID: 33794440
- DOI: 10.1016/j.ejca.2021.02.028
Pembrolizumab plus eribulin in hormone-receptor-positive, HER2-negative, locally recurrent or metastatic breast cancer (KELLY): An open-label, multicentre, single-arm, phase Ⅱ trial
Abstract
Background: Pembrolizumab has modest activity if used in patients with hormone-receptor-positive (HR+), HER2-negative, previously treated metastatic breast cancer (BC). Our study investigated whether there would be any clinical benefit in combining chemotherapy with pembrolizumab in a similar patient population.
Methods: This single-arm, phase Ⅱ trial enrolled women aged ≥18 years with HR+, HER2-negative, inoperable, locally recurrent or metastatic BC. Patients were previously treated with hormonal therapy and 1-2 chemotherapy regimens for locally recurrent and/or metastatic BC. On each 21-day cycle, patients received intravenous pembrolizumab 200 mg on day 1 and eribulin 1∙23 mg/m2 on days 1 and 8. The primary endpoint was the clinical benefit rate. Analysis of safety and activity was carried out in all patients who met the screening criteria and received at least 1 dose of study treatment. The trial is registered at ClinicalTrials.gov, NCT03222856.
Results: Of the 44 patients enrolled between January 29 and October 17, 2018, clinical benefit was achieved in 25 (56∙8%, 95% confidence interval [CI]: 41∙0-71∙7), objective response in 18 (40∙9%, 95% CI: 26∙3-56∙8), median progression-free survival was 6∙0 months (95% CI: 3∙7-8∙4), and 1-year overall survival was 59∙1% (95% CI: 45∙8-76∙2). The most common treatment-emergent adverse events (AEs) of any grade were neutropenia (20 [45∙5%]), anaemia (17 [38∙6%]), alopecia (19 [43∙2%]), asthenia (19 [43∙2%]), diarrhoea (14 [31∙8%]), fatigue (14 [31∙8%]), and peripheral neuropathy (12 [27∙3%]). Serious AEs occurred in 14 (31∙8%) patients including febrile neutropenia (3 [6∙8%]), neutropenia (2 [4∙5%]), fever (2 [4∙5%]) and peripheral neuropathy (2 [4∙5%]). Immune-related AEs occurred in 11 (25∙0%) patients. One (2∙3%) patient died of cardiac arrest unrelated to study treatment.
Conclusion: Pembrolizumab plus eribulin demonstrates encouraging antitumour activity in patients with heavily pre-treated, HR+, HER2-negative, locally recurrent or metastatic BC. The safety and tolerability of the combination is similar to eribulin or pembrolizumab monotherapy.
Keywords: Eribulin; HR-positive/HER2-negative metastatic breast cancer; PD-L1; Pembrolizumab.
Copyright © 2021 Elsevier Ltd. All rights reserved.
Conflict of interest statement
Conflict of interest statement M.G., G.C., J.L.A., B.B., L.C., V.C., S.C.S., R.M.V., M.R.B., and J.S. have nothing to declare. The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: J.M.P.-G. reports to have a consulting role for Roche, Lilly, and MEDSIR, and travel expenses from Roche. A.L.-C. reports leadership for Eisai, Celgene, Lilly, Pfizer, Roche, Novartis, and MSD, intellectual property for MEDSIR and Initia-Research; reports to have a consulting role for Lilly, Roche, Pfizer, Novartis, Pierre-Fabre, GenomicHealth, and GSK; to be part of speaker bureau for Lilly, AstraZeneca, and MSD; research funding from Roche, Foundation Medicine, and Pierre-Fabre, Agendia; and travel expenses from Roche, Lilly, Novartis, Pfizer, and AstraZeneca. E.L.-M. reports to have a consulting role for MEDSIR. A.P. reports honoraria from Pfizer, Novartis, Roche, MSD Oncology, Lilly, Daiichi Sankyo, Amgen, to have a consulting role for Amgen, Roche, Novartis, Pfizer, Brystol-Myers Squibb, Boehringer, PUMA Biotechnology, Oncolytics Biotech, Daiichi Sankyo, Abbvie, NanoString Technologies; research funding to the Institution from Roche, Novartis, Incyte, PUMA Biotechnology; to have intellectual property (PCT/EP2016/080056: HER2 AS A PREDICTOR OF RESPONSE TO DUAL HER2 BLOCKADE IN THE ABSENCE OF CYTOTOXIC THERAPY; WO/2018/096191. Chemoendocrine score (CES) Based on PAM50 for breast cancer with positive hormone receptors with an intermediate risk of recurrence); travel expenses from Daiichi Sankyo; other relationship with Oncolytics, Peptomyc S.L.; and that an immediate family member is an employee of Novartis. M.S.-C. reports honoraria from MEDSIR, Syntax for Science, and Nestlé; to have a consulting role for MEDSIR, Syntax for Science, and Nestlé; to be part of speaker bureau for MEDSIR, Syntax for Science, Roche; research funding from MEDSIR, Syntax for Science, and Roche; and travel expenses from MEDSIR, Syntax for Science, and Roche. M.A.S.-P. reports to have research funding to the Institution from Roche, Novartis; honoraria from Roche, Pfizer, Novartis, Amgen, Eisai, MSD; and non-financial support from Roche, Pfizer, Novartis, Amgen, Eisai. A.M. is a full-time employee of MEDSIR. P.S. reports to have honoraria from Pfizer, AstraZeneca, Novartis, Roche, Merck, Boehringer Ingelheim; consulting or advisory role from Pfizer, AstraZeneca, Novartis, Roche, Merck, Boehringer Ingelheim, Bayer, Eisai, Celgene, Puma; and grant to institution from Roche, Genentech, Oncogenex, Novartis. J.C. reports to have a consulting role for Roche, Celgene, Cellestia, AstraZeneca, Biothera Pharmaceutical, Merus, Seattle Genetics, Daiichi Sankyo, Erytech, Athenex, Polyphor, Lilly, Servier, Merck Sharp & Dohme, GSK, Leuko, Bioasis, and Clovis Oncology; honoraria from Roche, Novartis, Celgene, Eisai, Pfizer, Samsung Bioepis, Lilly, Merck Sharp & Dohme, and Daiichi Sankyo; research funding to the Institution from Roche, Ariad pharmaceuticals, AstraZeneca, Baxalta GMBH/Servier Affaires, Bayer Healthcare, Eisai, F.Hoffman-La Roche, Guardanth health, Merck Sharp & Dohme, Pfizer, Piqur Therapeutics, Puma C, and Queen Mary University of London; and intellectual property of MEDSIR.
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