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.

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/m

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.

Informations de copyright

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Déclaration de conflit d'intérêts

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.