Patterns of failure and efficacy for unresectable or recurrent gastric and gastroesophageal junction adenocarcinoma after immune checkpoint inhibitor therapy: A retrospective study.

Abstract

e16491 Background: Immune checkpoint inhibitors (ICIs) combined with chemotherapy have been incorporated into clinical guidelines in multiple countries as a first-line treatment regimen for advanced gastric cancer. However, data regarding the patterns of failure associated with ICIs remain limited, and the optimal strategy for subsequent treatment remains controversial. Herein, we investigated the patterns of treatment failure following immunotherapy in patients with unresectable or recurrent gastric and gastroesophageal junction adenocarcinoma and further elucidated the impact of subsequent treatment strategies on patient outcomes. Methods: We retrospectively analyzed 193 patients with unresectable or recurrent gastric or gastroesophageal junction adenocarcinoma who received immune checkpoint inhibitor (ICI) combined with chemotherapy between January 2022 and April 2025. Kaplan–Meier method and log-rank test were used to perform survival analyses of different progression patterns and subsequent treatment strategies. Results: In the entire study cohort, a total of 152 patients (78.7%) experienced disease progression. Among the patients, the most common site of progression was the liver (n = 39, 25.7%), followed by the primary site or regional lymph nodes (n = 36, 23.7%) and peritoneal metastasis (including malignant ascites) (n = 26, 17.1%). Furthermore, oligoprogression occurred in 85 patients (55.9%), while 67 patients (44.1%) exhibited systemic progression. Patients with oligoprogression had both a longer median progression-free survival (PFS) (6.5 months vs. 4.7 months, P = 0.003) and a longer median overall survival (OS) (16.7 months vs. 9.9 months, P = 0.001) compared to those with systemic progression. Among patients who progressed after immunotherapy, continued application of chemotherapy (16.73 months vs. 8.33 months, P < 0.001) or immunotherapy (17.83 months vs. 9.63 months, P = 0.001) prolonged the median OS. Patients who received radiotherapy after progression showed a trend towards longer median OS compared to those who did not (15.90 months vs. 11.97 months, P = 0.06). Conclusions: Oligoprogression is the most common pattern of failure following immunotherapy for gastric cancer, with liver metastasis being the most frequent site of progression. Subsequent treatment with either chemotherapy or immunotherapy after disease progression is associated with improved survival. Receiving radiotherapy after progression shows a trend toward prolonged survival, suggesting its potential as an effective subsequent-line treatment.