Retreatment with immune checkpoint inhibitors (ICIs) for patients with advanced gastric cancer: A retrospective, real-world study.

343 Background: Immunotherapy combined with chemotherapy has become the standard first-line treatment for advanced gastric cancer and is recommended by multiple guidelines and consensuses. After the first line immunotherapy, there is still controversy over whether immune inhibitors can continue to be used across lines after progression. Methods: This is a single-center, retrospective, observational, real-world study. We collected clinical information of patients with advanced gastric cancer hospitalized at the First Affiliated Hospital of Zhengzhou University from January 2018 to July 2024. All patients received combination therapy with ICIs inhibitors for at least 2 cycles in the first-line and at least 2 cycles of ICI inhibitor-based therapy in the second-line after first-line progression. The efficacy and safety of treatment were evaluated, including overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), the progression pattern of retreatment with immune checkpoint inhibitor, grade 3-5 treatment-related adverse events (TRAEs), and immune-related adverse events (irAEs). Cox regression model was used to investigate the influence of multiple factors on survival. Results: We included 217 patients with a median age of 59.0 (18-84) years, of which 70.0% were male. The median OS and PFS were 9.8 (95% CI 8.8-10.8) months and 4.6 (95% CI 4.0-5.3) months. The ORR and DCR were 22.7% (95% CI 17.1-29.0) and 56.2% (95% CI 49.0-63.1). For the second-line treatment regimens, there were 87 (40.1%) patients and 130 (59.9%) patients received immunotherapy combined with chemotherapy (I+C) and immunotherapy combined with chemotherapy and anti-angiogenic drugs(I+C+A) respectively. The median OS was 9.3 (95% CI 8.5-10.1) months and 11.5 (95% CI 9.3-13.7) months, p=0.032. The median PFS was 4.2 (95% CI 3.1-5.3) months and 5.2 (95% CI 4.3-6.1) months, p=0.082. Cox regression model analysis showed that ECOG 0-1, PFS≥6 months in the first-line treatment, second-line regimen (I+C+A), and second-line medication &gt; 3 cycles were independent prognostic factors for OS in the second-line treatment. The incidence of grade ≥3 TRAEs was 20.7%, and the incidence of irAEs was 6.5%. No treatment-related deaths occurred. Conclusions: This real-world study results showed that retreatment with immune checkpoint inhibitors had promising clinical benefit for patients with advanced gastric cancer and manageable safety. Efficacy of different groups. n mOS（m） mPFS（m） ORR（%） DCR（%） ITT 217 9.8 4.6 22.7 56.2 ECOG 0-1 180 9.8 4.7 19.5 56.8 2 37 8.6 4.0 38.2 52.9 1-Line PFS ＜3m 61 5.5 2.2 1.7 17.2 ≥3m 156 11.7 6.0 31.0 71.7 ＜6m 136 7.4 3.2 2.4 38.7 ≥6m 81 15.1 8.0 54.4 83.5 Second-line treatment I+C 87 9.3 4.2 16.9 54.2 <jats: