Health-Related Quality of Life With Nivolumab Plus Chemotherapy Versus Chemotherapy in Patients With Advanced Gastric/Gastroesophageal Junction Cancer or Esophageal Adenocarcinoma From CheckMate 649

Abstract

Purpose: In CheckMate 649, first-line nivolumab plus chemotherapy prolonged overall survival versus chemotherapy in patients with advanced/metastatic non-human epidermal growth factor receptor 2 (HER2)-positive gastric/gastroesophageal junction cancer (GC/GEJC) or esophageal adenocarcinoma (EAC). We present exploratory patient-reported outcomes (PROs).

Methods: In patients (N = 1,581) concurrently randomly assigned 1:1 to nivolumab plus chemotherapy or chemotherapy and in those with tumor PD-L1 expression at a combined positive score (CPS) of ≥5, health-related quality of life (HRQoL) was assessed using the EQ-5D and Functional Assessment of Cancer Therapy-Gastric (FACT-Ga), which included the FACT-General (FACT-G) and Gastric Cancer subscale (GaCS). The FACT-G GP5 item assessed treatment-related symptom burden. Longitudinal changes in HRQoL were assessed using mixed models for repeated measures in the PRO analysis population (randomly assigned patients with baseline and ≥1 postbaseline assessments). Time to symptom or definitive deterioration analyses were also conducted.

Results: In the PRO analysis population (n = 1,360), PRO questionnaire completion rates were mostly >80% during treatment. Patient-reported symptom burden was not increased with nivolumab plus chemotherapy versus chemotherapy. Mean improved changes from baseline were greater with nivolumab plus chemotherapy versus chemotherapy for FACT-Ga total, GaCS, and EQ-5D visual analog scale in patients with a CPS of ≥5; results were similar for the overall PRO analysis population. In CPS ≥5 and all randomly assigned populations, nivolumab plus chemotherapy reduced the risk of symptom deterioration versus chemotherapy, on the basis of FACT-Ga total score and GaCS; time to definitive deterioration was longer, and the risk of definitive deterioration in HRQoL was reduced with nivolumab plus chemotherapy across EQ-5D and most FACT-Ga measures (hazard ratio [95% CI] <1).

Conclusion: Compared with chemotherapy alone, first-line nivolumab plus chemotherapy showed stable or better on-treatment HRQoL in patients with advanced/metastatic non-HER2-positive GC/GEJC/EAC and also showed decreased risk of definitive HRQoL deterioration.

Trial registration: ClinicalTrials.gov NCT02872116.

FIG 1.

Least-squares mean change (95% CI) from baseline in (A) FACT-Ga total score, (B) GaCS, (C) EQ VAS, and (D) EQ-5D UI scores in the CPS ≥5 PRO analysis population. Dashed lines indicate MCTs. Circles indicate point estimates, and vertical bars indicate 95% CIs. *P < .05 was not formally tested. Only timepoints with ≥10 patients per treatment arm were included. Chemo, chemotherapy; CPS, combined positive score; EQ-5D UI, EQ-5D utility index; EQ VAS, EQ-5D visual analog scale; FACT-Ga, Functional Assessment of Cancer Therapy-Gastric; GaCS, Gastric Cancer Subscale; MCT, meaningful change threshold; NIVO, nivolumab; PRO, patient-reported outcome.

FIG 2.

Least-squares mean change (95% CI) from baseline in (A) FACT-Ga total score, (B) GaCS, (C) EQ VAS, and (D) EQ-5D UI scores in the overall PRO analysis population. Dashed lines indicate MCTs. Circles indicate point estimates, and vertical bars indicate 95% CIs. *P < .05 was not formally tested. Only timepoints with ≥10 patients per treatment arm were included for FACT-Ga total score, GaCS, and EQ VAS; timepoints with ≥20 patients per treatment arm were included for EQ-5D UI. Chemo, chemotherapy; CPS, combined positive score; EQ-5D UI, EQ-5D utility index; EQ VAS, EQ-5D visual analog scale; FACT-Ga, Functional Assessment of Cancer Therapy-Gastric; GaCS, Gastric Cancer Subscale; MCT, meaningful change threshold; NIVO, nivolumab; PRO, patient-reported outcomes.

FIG 3.

TTSD on the basis of FACT-Ga total score and GaCS in the (A and B) CPS ≥5 and (C and D) all randomly assigned populations. ^aOne hundred twenty-five (26.4%) patients in the NIVO + chemo arm and 122 (25.3%) patients in the chemo arm showed symptom deterioration; ^b116 (24.5%) patients in the NIVO + chemo arm and 127 (26.3%) patients in the chemo arm showed symptom deterioration; ^cMCTs were 15.1 points for FACT-Ga total score and 8.2 points for GaCS; ^dP < .05 was not formally tested; ^e213 (27.0%) patients in the NIVO + chemo arm and 200 (25.2%) patients in the chemo arm showed symptom deterioration; ^f199 (25.2%) patients in the NIVO + chemo arm and 195 (24.6%) patients in the chemo arm showed symptom deterioration. Chemo, chemotherapy; CPS, combined positive score; FACT-Ga, Functional Assessment of Cancer Therapy-Gastric; GaCS, Gastric Cancer Subscale; HR, hazard ratio; MCT, meaningful change threshold; NE, nonestimable; NIVO, nivolumab; PRO, patient-reported outcomes; TTSD, time to symptom deterioration.

FIG 4.

TTSD and TTDD in the (A) CPS ≥5 and (B) all randomly assigned populations for all PRO measures. HR reports NIVO + chemo versus chemo. Chemo, chemotherapy; CPS, combined positive score; EQ-5D UI, EQ-5D utility index; EQ VAS, EQ-5D visual analog score; EWB, emotional well-being subscale; FACT-G, Functional Assessment of Cancer Therapy-General; FACT-Ga, Functional Assessment of Cancer Therapy-Gastric; FWB, functional well-being subscale; GaCS, Gastric Cancer Subscale; HR, hazard ratio; NIVO, nivolumab; PRO, patient-reported outcome; PWB, physical well-being subscale; SWB, social well-being subscale; TTSD, time to symptom deterioration; TTDD, time to definitive deterioration.

FIG 5.

Time to definitive deterioration on the basis of FACT-Ga total score and GaCS in the (A and B) CPS ≥5 and (C and D) all randomly assigned populations. ^aSeventy-two (15.2%) patients in the NIVO + chemo arm and 79 (16.4%) patients in the chemo arm showed definitive deterioration; ^b75 (15.9%) patients in the NIVO + chemo arm and 85 (17.6%) patients in the chemo arm showed definitive deterioration; ^cMCTs were 15.1 points for FACT-Ga total score and 8.2 points for GaCS; ^dP <.05 was not formally tested; ^e131 (16.6%) patients in the NIVO + chemo arm and 132 (16.7%) patients in the chemo arm showed definitive deterioration; ^f129 (16.3%) patients in the NIVO + chemo arm and 131 (16.5%) patients in the chemo arm showed definitive deterioration. Chemo, chemotherapy; CPS, combined positive score; FACT-Ga, Functional Assessment of Cancer Therapy-Gastric; GaCS, Gastric Cancer Subscale; HR, hazard ratio; MCT, meaningful change threshold; NE, nonestimable; NIVO, nivolumab; TTDD, time to definitive deterioration.