Health-related quality of life in advanced gastric/gastroesophageal junction cancer with second-line pembrolizumab in KEYNOTE-061

Abstract

Background: In the primary analysis population (i.e., PD-L1 combined positive score [CPS] ≥ 1) of the phase 3 KEYNOTE-061 study (NCT02370498), pembrolizumab did not significantly prolong overall survival or progression-free survival. Pembrolizumab had a favorable safety profile in the all-patient population. We present results of prespecified health-related quality of life (HRQoL) analyses.

Methods: HRQoL was measured using the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30), EORTC QLQ gastric cancer questionnaire (QLQ-STO22), and EuroQol 5-dimension, 3-level questionnaire (EQ-5D-3L). Data were analyzed from patients who received ≥ 1 dose of study treatment and who completed ≥ 1 HRQoL assessment. Key analyses included baseline to week 12 least-squares mean (LSM) change in global health status (GHS)/QoL, functional/symptom subscales, and time to deterioration (TTD; ≥ 10-point decrease from baseline) for specific subscales.

Results: The HRQoL population included 371 patients (pembrolizumab, n = 188; paclitaxel, n = 183). Compliance and completion rates for all 3 questionnaires were similar in both groups at baseline and week 12. There was no difference in LSM change between groups (- 3.54; 95% CI - 8.92 to 1.84) in GHS/QoL at week 12. LSM change from baseline to week 12 for most QLQ-C30, QLQ-STO22, and EQ-5D-3L subscales indicated some worsening of QoL in both groups. TTD for GHS/QoL, nausea/vomiting, and appetite loss subscales in QLQ-C30 and the pain subscales in QLQ-STO22 were similar between treatment groups.

Conclusions: In this population with advanced gastric and GEJ cancer receiving second-line treatment, HRQoL was similar in patients receiving pembrolizumab and those receiving paclitaxel.

Clinical trial registry and number: ClinicalTrials.gov, NCT02370498.

Keywords: Chemotherapy; Gastric cancer; HRQoL; Pembrolizumab.

Conflict of interest statement

E. Van Cutsem has received research funding (to his institution) from Amgen, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Ipsen, Lilly, Merck KGaA, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, Novartis, Roche, and Servier. He has also served in an advisory/consultancy role for Astellas, AstraZeneca, Bayer, Bristol Myers Squibb, Celgene, Incyte, Lilly, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, Merck KGaA, Novartis, Roche, and Servier. M. Amonkar reports employment at Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, and is stockholder of Merck & Co., Inc., Kenilworth, NJ, USA. C. S. Fuchs served in an advisory/consultancy role for Agios, Amylin Pharmaceuticals, Bain Capital, CytomX Therapeutics, Daiichi-Sankyo, Eli Lilly, Entrinsic Health, EvolveImmune Therapeutics, Genentech, Merck, Taiho, and Unum Therapeutics. He also serves as a director for CytomX Therapeutics and owns unexercised stock options for CytomX and Entrinsic Health. He is a cofounder of EvolveImmune Therapeutics and has equity in this private company. M. Alsina has received honoraria from Bristol Myers Squibb, Lilly, MSD, and Servier and served in an advisory/consultancy role for Bristol Myers Squibb, Lilly, MSD, and Servier. M. Özgüroğlu has received honoraria (personal and to his institution) from Astellas, Janssen, Novartis, Roche, and Sanofi; served in an advisory/consultancy role for Astellas, Janssen, and Sanofi; and received travel/accommodations from AstraZeneca, Bristol Myers Squibb, and Janssen. Y.-J. Bang served in an advisory/consultancy role for AstraZeneca, Novartis, Genentech/Roche, MSD, Merck Serono, Bayer, Bristol Myers Squibb, Eli Lilly, Taiho, Daiichi-Sankyo, Astellas, BeiGene, GreenCross, Samyang Biopharm, Hanmi, and Genexine and received research grant/funding (to his institution) from MSD, AstraZeneca, Novartis, Genentech/Roche, Merck Serono, Bayer, Bristol Myers Squibb, GlaxoSmithKline, Pfizer, Eli Lilly, Boehringer Ingelheim, MacroGenics, Boston Biomedical, FivePrime, Curis, Taiho, Takeda, Ono, Daiichi Sankyo, Astellas, BeiGene, Green Cross, CKD Pharma, and Genexine. H. C. Chung has received honoraria from Merck Serono, Lilly, Foundation Medicine; served in an advisory/consultancy role for Taiho, Celltrion, MSD, Lilly, Quintiles, Bristol Myers Squibb, Merck Serono, Gloria, BeiGene, Amgen, and Zymeworks; and received research grants/funding (to his institution) from Lilly, GlaxoSmithKline, MSD, Merck Serono, Bristol Myers Squibb/Ono, Taiho, Amgen, and BeiGene. K. Muro has received honoraria for speaking from Bristol Myers Squibb, Eli Lilly, Chugai Pharmaceutical, Takeda Pharmaceutical, Taiho Pharmaceutical, Ono Pharmaceutical Co., Ltd., and Sanofi; served in an advisory/consultancy role for AstraZeneca, Amgen, and Ono Pharmaceutical Co., Ltd; and received research funding (to his institution) from MSD, Daiichi Sankyo, Parexel International, Sumitomo Dainippon Pharma, Pfizer, Mediscience Planning, Solasia Pharma, and Sanofi. E. Goekkurt has served in an advisory/consultancy role for Bristol Myers Squibb, Lilly, Merck KGaA, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, Roche, and Servier. A. Benson has served in an advisory/consultancy role for CN, Bristol Myers Squibb, Patient Resource (educational document review), Research to Practice, AVBCC, Harborside, Therabionic, Guardant, Merck (DMC), Terumo, Lexicon, ACCC, ECOG-ACRIN, Amgen, Imedex, Artemida Pharma, Intellisphere OncLiv, American College of Radiology, China National Medical Association 6th Affiliated Sun Yat-Sen Hospital, Springer, Health Advances, Lexicon, Array (Pfizer), NCCN, and ACCC. W. Sun has received research grant/funding (personal and to his institution) from Merck. Z. A. Wainberg has served in an advisory/consultancy role for AstraZeneca, Bayer, Daiichi, Five Prime, Lilly, Merck, and Molecular Templates; received funding (to his institution) from AstraZeneca, Daiichi, Five Prime, Lilly, and Merck; and received travel/accommodations from Bayer, Daiichi, Lilly, Merck, and Molecular Templates. J. M. Norquist is an employee of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA and a stockholder in Merck & Co., Inc., Kenilworth, NJ, USA. X. Chen is an employee of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA and a stockholder in Merck & Co., Inc., Kenilworth, NJ, USA. C.-S. Shih is an employee of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA and a stockholder in Merck & Co., Inc., Kenilworth, NJ, USA. K. Shitara has received honoraria from AbbVie, Novartis, and Yakult; served in an advisory/consultancy role for Astellas Pharma, Lilly, Bristol Myers Squibb, Takeda, Pfizer, Ono Pharmaceutical, Taiho, MSD, Novartis, AbbVie, GlaxoSmithKline; and received research grants/funding (to his institution) from Lilly, Ono Pharmaceutical, Dainippon Sumitomo Pharma, MSD, Daiichi Sankyo, Taiho Pharmaceutical, Chugai Pharmaceutical, Astellas Pharma, and Mediscience.

© 2021. The Author(s).

Figures

Fig. 1

Mean (SE) EORTC QLQ-C30 GHS/QoL scores over time. EORTC European Organisation for Research and Treatment of Cancer, GHS global health status, Q3W every 3 weeks, QLQ-30 Quality of Life Questionnaire Core 30, QoL quality of life, SE standard error

Fig. 2

LSM (95% CI) change from baseline to week 12 in a EORTC QLQ-C30 GHS/QoL and functional subscale scores, b EORTC QLQ-C30 symptom subscale scores, and c EORTC QLQ-STO22 symptom subscale scores. EORTC European Organisation for Research and Treatment of Cancer, GHS global health status, LSM least-squares mean, Q3W every 3 weeks, QLQ-30 Quality of Life Questionnaire Core 30, QLQ-STO22 health-related QoL questionnaire in gastric cancer, QoL quality of life

Fig. 3

Proportion of patients with deteriorated or improved status in EORTC QLQ-C30 scores at week 12. a Pembrolizumab. b Paclitaxel. EORTC European Organisation for Research and Treatment of Cancer, GHS, global health status; QLQ-30 Quality of Life Questionnaire Core 30, QLQ-STO22, health-related QoL questionnaire in gastric cancer; QoL, quality of life

Fig. 4

TTD in the a EORTC QLQ-C30 GHS/QoL scale, b EORTC QLQ-C30 nausea/vomiting subscale, c EORTC QLQ-C30 appetite loss subscale, and d EORTC QLQ-STO22 pain subscale. GHS global health status, Q3W every 3 weeks, QLQ-30 Quality of Life Questionnaire Core 30, QLQ-STO22 health-related QoL questionnaire in gastric cancer, QoL quality of life, TTD time to deterioration