As reported in the Journal of Clinical Oncology, Markus Moehler, MD, and colleagues found that in the phase III CheckMate 649 trial, the addition of nivolumab to chemotherapy was associated with generally better patient-reported health-related quality of life outcomes in patients with advanced non–HER2-positive (HER2-negative or unknown HER2 status) gastric/gastroesophageal junction cancer or esophageal adenocarcinoma.
The trial supported the April 2021 approval of nivolumab in combination with fluoropyrimidine- and platinum-containing chemotherapy in advanced or metastatic gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma, regardless of PD-L1 expression status.
Markus Moehler, MD
Study Details
In the trial, a total of 1,581 patients were randomly assigned to receive nivolumab plus chemotherapy or chemotherapy alone. Of these, 1,360 (n = 694 and 666) were included in the patient-reported outcome analysis, including 822 (n = 422 and 400) with a PD-L1 combined positive score (CPS) of ≥ 5. Health-related quality of life was assessed with the EQ-5D visual analog scale (VAS) and Functional Assessment of Cancer Therapy-Gastric (FACT-Ga) instruments, which included the FACT-General (FACT-G) and Gastric Cancer subscale (GaCS). The FACT-G GP5 item assessed treatment-related symptom burden.
Key Findings
Patient-reported outcome questionnaire completion rates were generally > 80% during treatment. Patient-reported symptom burden was not increased with nivolumab/chemotherapy vs chemotherapy on the FACT-G GP5 item. Proportions of patients reporting “not at all bothered” by treatment-related side effects increased over time in the nivolumab/chemotherapy group and were higher vs those in the chemotherapy group at most postbaseline timepoints.
In the CPS ≥ 5 population, FACT-Ga total, GaCS, and EQ-5D VAS scores generally improved from baseline at most on-treatment assessments in both groups. Least-squared mean changes favored nivolumab/chemotherapy vs chemotherapy for each of the three measures. Similar outcomes were observed in the total patient-reported outcomes population.
In the CPS ≥ 5 population, patients in the nivolumab/chemotherapy group exhibited delayed time to symptom deterioration and reduced risk of symptom deterioration during treatment vs the chemotherapy group on FACT-Ga total score (hazard ratio [HR] = 0.75, 95% confidence interval [CI] = 0.58–0.97) and GaCS (HR = 0.65, 95% CI = 0.50–0.83). Similar findings were made in the total patient-reported outcomes population.
The investigators concluded, “Compared with chemotherapy alone, first-line nivolumab plus chemotherapy showed stable or better on-treatment health-related quality of life in patients with advanced/metastatic non–HER2-positive gastric/gastroesophageal junction cancer or esophageal adenocarcinoma and also showed decreased risk of definitive health-related quality of life deterioration.”
Hong Xiao, PhD, of Bristol Myers Squibb, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by Bristol Myers Squibb. For full disclosures of the study authors, visit ascopubs.org.
