Table 4.

HRQOL outcomes reported from GI cancer ICI registration trials

Study	Study population	Agents evaluated	PROs measured	Outcomes
CheckMate 577 (NCT02743494)	Patients with stage II/III E/GEJ cancer and residual pathological disease status post-NA chemoradiotherapy and an R0 resection	Adjuvant nivolumab Adjuvant placebo	FACT-E EQ-5D-3L	Trend toward improvement in both treatment groups from BL to week 49 for FACT-E total, ECS, and EQ-5D VAS and Utility Index scores
CheckMate 649 (NCT02872116)	Patients with advanced, untreated gastric, GEJ, and esophageal adenocarcinoma	Chemotherapy plus nivolumab Chemotherapy	Q-TWiST Relative Q-TWiST gains (Q-TWiST difference divided by chemo only OS) defined as clinically important (≥10%) and clearly clinically important (≥15%)	Q-TWiST improvement with addition of nivolumab to chemotherapy: PD-L1 CPS ≥5: 2.8 months (95% CI 1.0 to 3.7; relative gain 20.6% [clearly clinically important]) All randomized patients: 1.8 months (95% CI 0.9 to 2.7; relative gain 12.7% [clinically important])
KEYNOTE-062 (NCT02494583)	Patients with PD-L1-positive (CPS ≥1) advanced G/GEJ cancer and no prior treatment	Pembrolizumab monotherapy Pembrolizumab plus chemotherapy Chemotherapy	EORTC-QLQ-C30 EORTC-QLQ-STO22	LSM change in EORTC-QLQ-C30 GHS/QOL: no between-arm difference (−0.16; 95% CI −5.01 to 4.69; p=0.948) LSM TTD subscale changes: GHS/QOL: similar between arms (HR 0.96; 95% CI 0.67 to 1.38; p=0.826) Appetite loss: similar between arms (HR 0.83; 95% CI 0.58 to 1.20; p=0.314) Pain: similar between arms (HR 1.22; 95% CI 0.78 to 1.91; p=0.381) TTD for nausea/vomiting subsale: longer for pembrolizumab (HR 0.61; 95% CI 0.44 to 0.85; p=0.003)
KEYNOTE-177 (NCT02563002)	Patients with MSI-H or dMMR metastatic colorectal cancer with no prior treatment	Pembrolizumab Chemotherapy	EORTC-QLQ-C30 GHS/QOL	LSM change (BL to prespecified week 18): EORTC-QLQ-C30 GHS/QOL: clinically meaningful improvement for pembrolizumab versus chemotherapy (8.96 [95% CI 4.24 to 13.69]; two-sided nominal p=0.0002) Median TTD was longer with pembrolizumab versus chemotherapy: GHS/QOL (HR 0.61 [95% CI 0.38 to 0.98]; one-sided nominal p=0.019) Physical functioning (0.50 [95% CI 0.32 to 0.81]; one-sided nominal p=0.0016) Social functioning (0.53 [95% CI 0.32 to 0.87]; one-sided nominal p=0.0050) Fatigue (0.48 [95% CI 0.33 to 0.69]; one-sided nominal p<0.0001)
KEYNOTE-590 (NCT03189719)	Patients with locally advanced/unresectable or metastatic adenocarcinoma or ESCC or Siewert type 1 esophagogastric junction adenocarcinoma with no prior treatment	Chemotherapy plus pembrolizumab Chemotherapy plus placebo	EORTC-QLQ-C30 (GHS/QOL and physical functioning), TTD and change from BL to week 18 EORTC-QLQ-OES18 (pain, reflux, dysphagia), TTD and change from BL to week 18 EQ-5D-5L, TTD and change from BL to week 18	LSM change (BL to week 18) in GHS/QOL status: no difference between arms (−0.10 [95% CI −3.40 to 3.20]; p=0.9530) Median TTD in EORTC-QLQ-C30 GHS/QOL: no difference between treatment arms (HR 0.86 [95% CI 0.66 to 1.13]; p=0.2864) LSM changes (BL to 18 weeks) for EORTC-QLQ-OES18 subscales: Pain: pembrolizumab plus chemotherapy better (−2.94 [95% CI −5.86 to −0.02]; p=0.0487) Reflux: no difference between treatment arms (−1.19 [95% CI −4.49 to 2.10]; p=0.4781) Dysphagia: no difference between treatment arms (−2.35 [95% CI −7.78 to 3.07]; p=0.3945)

BL, baseline; CI, confidence interval; CPS, combined positive score; dMMR, mismatch repair deficient; ECS, esophageal cancer subscale; EQ-5D-VAS, EuroQol 5 dimension visual analogue scale; ESCC, esophageal squamous cell carcinoma; G, gastric; GEJ, gastroesophageal junction; GHS, global health status; GI, gastrointestinal; ICI, immune checkpoint inhibitor; LSM, least squares mean; MSI-H, microsatellite instability-high; NA, neoadjuvant; OS, overall survival; PD-L1, programmed death-ligand 1; PRO, patient-reported outcome; QOL, quality of life; TTD, time to deterioration.