Effects of sintilimab plus chemotherapy as first-line treatment on health-related quality of life in patients with advanced esophageal squamous cell carcinoma: results from the randomized phase 3 ORIENT-15 study

Abstract

Background: In ORIENT-15 study, sintilimab plus chemotherapy demonstrated significant improvement on overall survival (OS) versus placebo plus chemotherapy in first-line treatment of advanced esophageal squamous cell carcinoma (ESCC). Here, we report effect of sintilimab plus chemotherapy on health-related quality of life (HRQoL) in patients with advanced ESCC.

Methods: From December 14, 2018 to August 28, 2022, HRQoL was evaluated in all randomized patients using European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 items (QLQ-C30), EORTC Quality of Life Questionnaire Oesophageal Cancer Module 18 items (QLQ-OES18), and visual analogue scale (VAS) of the EuroQol five-dimensional five-level questionnaire (EQ-5D-5L). Mean scores of each scale were described by treatment group through week 60. Least-squares mean (LSM) score change from baseline through week 24 were analyzed using the mixed-model repeated-measures method. Time to the first onset of deterioration (TTD) and OS for each scale were estimated. Clinical Trials Registration: NCT03748134.

Findings: As of August 28, 2022, 689 of 690 enrolled patients were assessed for HRQoL analysis (sintilimab group: 340, placebo group: 349). Median follow-up was 32.2 months. Differences in LSM favored sintilimab over placebo for QLQ-C30 social functioning (LSM difference: 3.06, 95% CI: 0.55 to 5.57; P = 0.0170), pain (-2.24, 95% CI: -4.30 to -0.17; P = 0.0337), fatigue (-2.24, 95% CI: -4.46 to -0.02; P = 0.0479), constipation (-3.27, 95% CI -5.49 to -1.05; P = 0.0039), QLQ-OES18 pain (-1.77, 95% CI -3.11 to -0.43; P = 0.0097), trouble swallowing saliva (-2.09, 95% CI: -3.77 to -0.42; P = 0.0146), and choked when swallowing (-3.23, 95% CI: -5.60 to -0.86; P = 0.0076). TTD favored sintilimab over placebo for QLQ-OES18 dysphagia (Hazard ratio [HR]: 0.76, 95% CI: 0.61-0.94, P = 0.0104), and trouble swallowing saliva (HR: 0.48, 95% CI: 0.35-0.67, P < 0.0001). Improved OS were observed in patients with better performance in several functioning and symptom scales of QLQ-C30 and QLQ-QES18.

Interpretation: The statistically significant differences of several HRQoL scales and improvements in delayed deterioration observed in our study further support the use of sintilimab plus chemotherapy as first-line treatment for advanced ESCC.

Funding: This study was funded by Innovent Biologics and was co-funded by Eli Lilly.

Keywords: Cancer immunotherapy; Chinese patients; Esophageal squamous cell carcinoma; Health-related quality of life; Phase 3 clinical trial.

Fig. 1

CONSORT Flow chart of participants. Abbreviations: PD, progressive disease; AE, adverse event; ITT, intention-to-treat.

Fig. 2

Mean score change from baseline through week 60 in QLQ-C30 scales of GHS, physical functioning, social functioning, pain, and fatigue symptom, QLQ-OES18 scales of dysphagia, eating, and pain, and EQ-5D-5L VAS (A), and least-squares mean differences between treatment groups in all scales of QLQ-C30, QLQ-OES18 and EQ-5D-5L VAS (B).

Fig. 3

Forest plot for time to first deterioration in QLQ-C30, QLQ-QES18, and EQ-5D-5L VAS. Abbreviations: Chemo, chemotherapy; HR, hazard ratio; NC, not calculated.

Fig. 4

Kaplan–Meier plot of OS in patients with better and worse HRQoL performance at week 6 (A) and with better or worse change of HRQoL performance from baseline to week 6 (B) for QLQ-C30 and QLQ-OES18.