Focusing on clinical trial ineligibility: Nivolumab plus chemotherapy for patients with advanced gastric cancer.

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Background: Nivolumab demonstrates promising efficacy when combined with chemotherapy as first-line treatment in patients with advanced gastric cancer (AGC). However, a large proportion of patients are perceived as ineligible for clinical trials in clinical practice. The aim of this study is to analyze the treatment outcomes and safety among patients deemed ineligible in clinical trials for AGC. Methods: A retrospective examination was conducted involving 187 patients who received treatment for HER2-negative unresectable or recurrent AGC between December 2014 and October 2023 at six institutions. Eleven patients were excluded due to massive ascites or poor performance status (PS). Ineligible patients were defined as meeting any of the seven criteria: age 75 years or over, PS 2, bone marrow dysfunction, hepatic dysfunction, renal dysfunction, serious complications, and extended bone metastasis. Of the 104 patients meeting these criteria, individuals were divided into the ICI group (nivolumab plus chemotherapy) and the non-ICI group (chemotherapy only). A comparative assessment of survival outcomes and tumor responses between the two groups was performed. Additionally, the incidence of immune-related adverse events (irAE) in the ICI group was assessed. Results: The ICI group comprised 57 patients, while the non-ICI group comprised 47 patients. The median follow-up for survival analysis was 11.6 months. In the ICI group, response rate (RR), median progression-free survival (mPFS), and median overall survival (mOS) were 48.7% among patients with measurable lesions, 7.4 months (95%CI, 5.3-10.0), and 15.1 months (95%CI, 13.1-21.0). In the non-ICI group, RR, mPFS, and mOS were 33.3%, 6.4 months (95%CI, 4.1-7.8), and 11.8 months (95%CI, 10.1-14.6). The OS in the ICI group was significantly better than those in the non-ICI group (log-rank p = 0.0436). Furthermore, irAEs were observed in eight patients (14.0%), including hypothyroidism (n=3), arthritis (n=2), hypopituitarism (n=2), and dermatitis (n=1). No patients discontinued treatment due to intolerable irAEs. Conclusions: The combination of nivolumab and chemotherapy showed a favorable outcome even in AGC patients with ineligible group.