Health-related quality of life (HRQoL) impact of pembrolizumab (pembro) versus best supportive care (BSC) in previously systemically treated patients (pts) with advanced hepatocellular carcinoma (HCC): KEYNOTE-240

Background KEYNOTE-240 (ClinicalTrials.gov: NCT02702401) is a double-blind, randomized, placebo-controlled, phase 3 trial that evaluated pembro 200 mg every 3 weeks compared with BSC in pts with advanced HCC who were previously systemically treated. Pembro reduced the risk of death by 22% and improved progression-free survival over BSC in pts with advanced HCC, although significance was not reached per prespecified statistical criteria. Here we present the results of prespecified exploratory HRQoL analyses. Methods The EORTC QLQ-C30 and EORTC QLQ-HCC18 questionnaires were administered electronically at baseline; weeks 3, 6, 9, 12, and 18; every 9 weeks thereafter up to 1 year or end of treatment; and at the 30-day safety follow-up visit. Least squares mean (LSM) score changes from baseline to week 12 (prespecified) were compared using constrained longitudinal data analysis model including treatment by study visit interaction and stratification factors as covariates. Time to deterioration (TTD) (≥10-point decline from baseline) was estimated by Kaplan-Meier method, and the magnitude of the treatment difference (hazard ratio) between treatment arms was assessed by a stratified Cox proportional hazards model. Results Pts receiving ≥1 dose of study treatment and completing ≥1 HRQoL assessment were included in the analysis. The HRQoL population included 398 pts (271 pembro; 127 BSC). HRQoL compliance at week 12 was 90.0% for pembro and 89.3% for BSC. From baseline to week 12, there was no statistically significant difference in LSM between the 2 arms for global health status (GHS)/QoL score (-1.19; 95% CI, -5.35, 2.97; P = 0.573). The GHS/QOL scores remained stable over time for both arms. TTD for prespecified symptoms of abdominal swelling (HR, 1.08; 95% CI, 0.76, 1.54; P = 0.6552), fatigue (HR, 0.98; 95% CI, 0.71, 1.20; P = 0.2795), and pain (HR, 0.97; 95% CI, 0.74, 1.27; P = 0.4078) from EORTC QLQ-HCC18 were similar between the 2 arms. Conclusions Over 12 weeks, pts treated with pembro had similar HRQoL compared to pts receiving BSC. Along with efficacy and safety results from KN240, these data support the benefit of pembrolizumab in HCC pts. Clinical trial identification NCT02702401; Release date: March 8, 2016. Editorial acknowledgement Harleigh E. Willmott, CMPP (ApotheCom, Yardley, PA, USA, funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. Legal entity responsible for the study Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. Funding Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. Disclosure P. Merle: Advisory / Consultancy, Leadership role, Research grant / Funding (institution): Onxeo; Advisory / Consultancy: Bayer; Advisory / Consultancy: MSD; Advisory / Consultancy, Research grant / Funding (institution): Ipsen; Advisory / Consultancy: Eisai; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Roche; Advisory / Consultancy: BMS. A.S. Kulkarni: Shareholder / Stockholder / Stock options, Full / Part-time employment: Merck Sharp & Dohme Corp. A. Cheng: Honoraria (self): Bayer; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Eisai; Honoraria (self): MSD; Honoraria (self), Advisory / Consultancy: Merck Serono; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Novartis; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Ono Pharmaceutical; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Roche/Genentech; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: IQVIA; Advisory / Consultancy: Bayer Schering Pharma; Advisory / Consultancy: BMS; Advisory / Consultancy: Exilixis; Advisory / Consultancy: Nucleix Ltd; Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Bayer Yakuhin, Ltd.; Speaker Bureau / Expert testimony: Amgen Taiwan. M. Kudo: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Eisai; Honoraria (self): Bayer; Honoraria (self), Advisory / Consultancy: MSD; Advisory / Consultancy, Research grant / Funding (institution): Ono; Advisory / Consultancy: BMS; Advisory / Consultancy: Eli Lilly; Research grant / Funding (institution): EA Pharma; Research grant / Funding (institution): Gilead; Research grant / Funding (institution): Takeda; Research grant / Funding (institution): Otsuka; Research grant / Funding (institution): Taiho. M. Bouattour: Advisory / Consultancy, Travel / Accommodation / Expenses: Bayer Pharma; Advisory / Consultancy, Travel / Accommodation / Expenses: BMS; Advisory / Consultancy: Eisai; Advisory / Consultancy, Travel / Accommodation / Expenses: Sirtex Medical; Advisory / Consultancy, Travel / Accommodation / Expenses: Ipsen. H.Y. Lim: Honoraria (self), Advisory / Consultancy: Bayer; Honoraria (self), Advisory / Consultancy: Eisai. V. Breder: Travel / Accommodation / Expenses: Roche; Travel / Accommodation / Expenses: MSD; Travel / Accommodation / Expenses: Bayer; Travel / Accommodation / Expenses: BMS; Travel / Accommodation / Expenses: Eisai; Travel / Accommodation / Expenses: BioCad. J. Edeline: Honoraria (self), Honoraria (institution), Research grant / Funding (self): BTG; Honoraria (self): Eisai; Honoraria (self): Ipsen; Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self): Novartis; Honoraria (self): Bayer; Advisory / Consultancy, Research grant / Funding (self), Travel / Accommodation / Expenses: BMS; Advisory / Consultancy, Travel / Accommodation / Expenses: MSD; Travel / Accommodation / Expenses: Amgen; Travel / Accommodation / Expenses: Servier; Travel / Accommodation / Expenses: Roche. S. Ogasawara: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Bayer; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Eisai; Honoraria (self), Advisory / Consultancy: Eli Lilly; Advisory / Consultancy: Merck Sharp & Dohme Corp.; Advisory / Consultancy: Chugai Pharma; Advisory / Consultancy: AstraZeneca. T. Yau: Honoraria (self), Advisory / Consultancy: MSD; Honoraria (self), Advisory / Consultancy: BMS. M. Garrido: Speaker Bureau / Expert testimony: Bayer; Speaker Bureau / Expert testimony, Research grant / Funding (institution): BMS; Speaker Bureau / Expert testimony: MSD; Research grant / Funding (institution): Pfizer. B. Daniele: Honoraria (self), Advisory / Consultancy: Ipsen; Honoraria (self): Lilly; Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Bayer; Honoraria (self), Travel / Accommodation / Expenses: BMS; Honoraria (self): MSD; Advisory / Consultancy: Eisai; Advisory / Consultancy: Incyte; Travel / Accommodation / Expenses: Sanofi. J. Norquist: Shareholder / Stockholder / Stock options, Full / Part-time employment: Merck Sharp & Dohme Corp. E. Chen: Full / Part-time employment: Merck Sharp & Dohme Corp. A.B. Siegel: Shareholder / Stockholder / Stock options, Full / Part-time employment: Merck Sharp & Dohme Corp. A.X. Zhu: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Eli Lilly; Advisory / Consultancy: Eisai; Advisory / Consultancy, Research grant / Funding (institution): BMS; Advisory / Consultancy, Research grant / Funding (institution): Merck Sharp & Dohme Corp.; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy: Sanofi; Research grant / Funding (institution): Bayer; Advisory / Consultancy: Exelixis. R.S. Finn: Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Bayer; Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy: Eisai; Advisory / Consultancy: Eli Lilly; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Merck Sharp & Dohme Corp.; Advisory / Consultancy: Roche/Genentech; Speaker Bureau / Expert testimony: Novartis. All other authors have declared no conflicts of interest.