Health-related quality of life in patients treated with pembrolizumab for microsatellite instability-high/mismatch repair-deficient advanced solid tumours: Results from the KEYNOTE-158 study

Abstract

Background: In the KEYNOTE-158 study (NCT02628067), pembrolizumab showed a high objective response rate and durable clinical benefit for patients with previously treated, unresectable/metastatic microsatellite instability-high (MSI-H)/mismatch repair‒deficient (dMMR) non-colorectal solid tumours. We present health-related quality of life (HRQoL) results from the MSI-H/dMMR population (cohort K).

Patients and methods: Eligible patients had previously treated MSI-H/dMMR advanced non-colorectal solid tumours, measurable disease per RECIST v1.1, and ECOG performance status ≤1. Patients received pembrolizumab 200 mg Q3W for 35 cycles (2 years). The EORTC Quality of Life Questionnaire (QLQ-C30) and EQ-5D-3L were administered at baseline, at regular intervals throughout treatment, and 30 days after treatment discontinuation. Prespecified analyses (exploratory endpoints) included the magnitude of change from baseline to post-baseline timepoints in all patients and by the best overall response for QLQ-C30 global health status (GHS)/QoL, QLQ-C30 functional/symptom scales/items, and EQ-5D-3L visual analogue scale (VAS) score.

Results: At data cutoff (October 5, 2020), 351 patients were enrolled, of whom 311 and 315 completed baseline QLQ-C30 and EQ-5D-3L questionnaires, respectively. QLQ-C30 GHS/QoL scores improved from baseline to week 9 (mean [95% CI] change, 3.07 [0.19-5.94]), then remained stable or improved by week 111, with greater improvements observed in patients with a best response of complete response (CR) or partial response (PR) (10.85 [6.36-15.35]). Patients with CR/PR showed improvements in physical (5.58 [1.91-9.25]), role (9.88 [3.80-15.97]), emotional (5.62 [1.56-9.68]), and social (8.33 [2.70-13.97]) functioning, and stable cognitive functioning (1.74 [-1.45 to 4.94]).

Conclusions: Pembrolizumab generally improved or preserved HRQoL in patients with previously treated MSI-H/dMMR advanced non-colorectal solid tumours.

Keywords: Health-related quality of life; Microsatellite instability; Pembrolizumab.

Conflict of interest statement

Conflict of Interest Statement The authors declare the following financial interests/personal relationships, which may be considered as potential competing interests. Michele Maio: study funding to the institution from Merck Sharp & Dohme LLC, and Merck & Co., Inc., Rahway, NJ, USA, to support study conduct; honoraria for serving as a speaker from MSD, Roche, Bristol Myers Squibb (BMS), Sanofi, AstraZeneca, Amgen, Pierre Fabre, Eli Lilly, GlaxoSmithKline (GSK), Sciclone, Alfasigma, and Merck Serono; personal fees for advisory boards from Merck Sharp & Dohme LLC, Roche, BMS, Incyte, AstraZeneca, Amgen, Pierre Fabre, Eli Lilly, Sanofi, GSK, Alfasigma, and Merck Serono; stockholder in Epigen Therapeutics and Theravance. Mayur M. Amonkar: employee of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. Owns stock in Merck & Co., Inc., Rahway, NJ, USA. Josephine M. Norquist: employee of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. Owns stock in Merck & Co., Inc., Rahway, NJ, USA. Paolo A. Ascierto: research funding from Bristol Myers Squibb, Roche-Genentech, Array, and Sanofi; personal fees for advisory/consultant role for Bristol Myers Squibb, Roche-Genentech, MSD, Array, Novartis, Merck Serono, Pierre Fabre, Incyte, MedImmune, AstraZeneca, Syndax, Sun Pharma, Sanofi, Idera, Ultimovacs, Sandoz, Immunocore, 4SC, Alkermes, Nektar, Italfarmaco, Boehringer-Ingelheim, Eisai, Regeneron, Daiichi Sankyo, Pfizer, Oncosec, Nouscom, Lunaphore, and Seagen; personal fees for travel support from MSD; unpaid consultant for Takis. Ludmila Manzyuk: nothing to disclose. Daniel Motola-Kuba: research funding from Roche/Genentech, Novartis, Amgen, Bristol Myers Squibb, GlaxoSmithKline, Janssen, Eli Lilly, AstraZeneca, and MSD. Nicolas Penel: study funding to the institution from MSD to support study conduct; research funding to the institution from Bayer-HealthCare. Philippe A. Cassier: research funding from Roche/Genentech, Novartis, Amgen, Bristol Myers Squibb, Blueprint Medicines, GlaxoSmithKline, Janssen, Eli Lilly, Taiho Pharmaceutical, AstraZeneca, MSD, Celgene, AbbVie, Toray Industries, Transgene, Innate Pharma, and Loxo; personal fees from Roche/Genentech, Novartis, Amgen, Merck Serono, and AstraZeneca; nonfinancial support from Roche/Genentech, Novartis, AstraZeneca, MSD, and Plexxikon; travel accommodations from NETRIS Pharma. Giovanni Mendonca Bariani: research funding from mAbxience, MSD, and Bristol Myers Squibb; advisory role for Libbs. Ana De Jesus Acosta: research funding from AstraZeneca, Merck & Co., Inc., Rahway, NJ, USA; consulting for Merck & Co., Inc., Rahway, NJ, USA. Toshihiko Doi: honoraria from AbbVie, Astellas Pharma, Bristol Myers Squibb Japan, Oncolys BioPharma, Ono Pharmaceutical, and Taiho Pharmaceutical; consulting or advisory role for AbbVie, Amgen, Bayer, Boehringer Ingelheim, Daiichi Sankyo, MSD, Novartis, Otsuka, Rakuten Medical, Sumitomo Dainippon, Taiho Pharmaceutical, and Takeda; research funding to the institution from AbbVie, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, Eisai, Lilly Japan, Merck Serono, MSD, Novartis, Pfizer, Quintiles, Sumitomo Group, and Taiho Pharmaceutical. Federico Longo: honoraria from Amgen, Bayer, Bristol Myers Squibb, Celgene, Ferrer, Lilly, Merck, MSD, Roche, Sanofi, and SERVIER; consulting or advisory role for Amgen, Bayer, Bristol Myers Squibb, Lilly, MSD, Roche, and SERVIER; travel expenses from Amgen, Bayer, Bristol Myers Squibb, Celgene, Ferrer, Lilly, Merck, MSD, Roche, Sanofi, and SERVIER. Wilson H. Miller, Jr.: consulting role for Bristol Myers Squibb, Merck & Co., Inc., Rahway, NJ, USA, Roche, Novartis, Amgen, GSK, Mylan, and EMD Serono; honoraria from BMS, Merck, Roche, GSK, Novartis, Amgen, Mylan, and EMD Serono; grants to the institution from Merck, CIHR, CRS, Terry Fox Research Institute, Samuel Waxman Cancer Research Foundation, and CCSRI; current or past (within the prior two years) investigator in clinical trials for BMS, Novartis, GSK, Roche, AstraZeneca, Methylgene, MedImmune, Bayer, Amgen Merck, Incyte, Pfizer, Sanofi, Array, MiMic, Ocellaris Pharma, Astellas, and Alkermes. Do-Youn Oh: consultant or advisory board member for AstraZeneca, Novartis, Genentech/Roche, Merck Serono, Bayer, Taiho, ASLAN, Halozyme, Zymeworks, Bristol Myers Squibb/Celgene, BeiGene, Basilea, and Turning Point; research grant from AstraZeneca, Novartis, Array, Eli Lilly, Servier, BeiGene, MSD, and Handok. Maya Gottfried: nothing to disclose. Ruixue Wang: employee of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. Owns stock in Merck & Co., Inc., Rahway, NJ, USA. Kevin Norwood: employee of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. Owns stock in Merck & Co., Inc., Rahway, NJ, USA. Aurelien Marabelle: funding to institution during the conduct of the study from MSD; honorarium from MSD and Sanofi; research grants from Foundation MSD Avenir, Sanofi, and Bristol Myers Squibb; personal fees for speakers bureau from Bristol Myers Squibb, Sanofi, and MSD.

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