Liver Cancer (Jan 2024)

A Phase 3 Study of Pembrolizumab Versus Placebo for Previously Treated Patients From Asia With Hepatocellular Carcinoma: Health-Related Quality of Life Analysis From KEYNOTE-394

  • Shukui Qin,
  • Weijia Fang,
  • Zhenggang Ren,
  • Shuangyan Ou,
  • Ho Yeong Lim,
  • Feng Zhang,
  • Kin Chung Lee,
  • Hye Jin Choi,
  • Jiandong Tong,
  • Min Tao,
  • Aibing Xu,
  • Ashley Cheng,
  • Chang-Hsien Lu,
  • Chang-Fang Chiu,
  • Mohamed Ibrahim Abdul Wahid,
  • Shital Kamble,
  • Josephine M. Norquist,
  • Wenyan Zhong,
  • Chen Li,
  • Zhendong Chen

DOI
https://doi.org/10.1159/000535338

Abstract

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Introduction KEYNOTE-394 showed pembrolizumab significantly improved overall survival, progression-free survival, and objective response rate with manageable safety versus placebo for patients from Asia with previously treated advanced hepatocellular carcinoma. We present results on health-related quality of life (HRQoL). Methods HRQoL was evaluated using the EORTC Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) and EuroQol-5D-3L (EQ-5D-3L) questionnaires. Key HRQoL endpoints were least squares mean (LSM) score changes from baseline to week 12 and time to deterioration (TTD) for EORTC QLQ-C30 global health status (GHS)/QoL. p values were one-sided and nominal without adjustment for multiplicity. Results The HRQoL population included patients randomly assigned to pembrolizumab (n = 298) and placebo (n = 152). From baseline to week 12, a greater decline in EORTC QLQ-C30 GHS/QoL score was observed with placebo (LSM, −8.4; 95% CI: −11.7 to −5.1) versus pembrolizumab (−4.0; 95% CI: −6.4 to −1.6; difference vs placebo: 4.4; 95% CI: 0.5–8.4; nominal p = 0.0142). Similarly, a greater decline in EQ-5D-3L visual analog scale score was observed with placebo (−6.9; 95% CI: −9.4 to −4.5) versus pembrolizumab (−2.7; 95% CI: −4.5 to −1.0; difference vs placebo: 4.2; 95% CI: 1.2–7.2; nominal p = 0.0030). TTD in EORTC QLQ-C30 GHS/QoL score was similar between arms (hazard ratio, 0.85; 95% CI: 0.58–1.25; nominal p = 0.1993). Conclusion Patients receiving placebo showed greater decline in HRQoL than those receiving pembrolizumab. Combined with efficacy and safety data from KEYNOTE-394 and the global KEYNOTE-240 and KEYNOTE-224 trials, our data support the clinically meaningful benefit and manageable tolerability of pembrolizumab as second-line therapy for patients with advanced hepatocellular carcinoma.