Continuing immune checkpoint inhibitors beyond progression versus switching to non-ICI therapy in advanced gastric...

The optimal second-line therapy for advanced gastric/gastroesophageal junction cancer (GC/GEJC) following progression on first-line immuno-chemotherapy remains undefined. This study aimed to compare the efficacy and safety of continuing an immune checkpoint inhibitor beyond progression (CIBP) versus switching to a non-ICI regimen (non-CIBP).

In this single-center, retrospective study, we enrolled 169 patients with GC/GEJC who progressed after first-line ICI plus chemotherapy. Based on the second-line therapeutic decision, patients were categorized into either the CIBP group (n=120; to continue ICI with or without combined therapy) or the non-CIBP group (n=49; to switch to a non-ICI regimen). The primary endpoints were progression-free survival (PFS) and overall survival (OS).

The CIBP group demonstrated significantly improved median PFS (4.4 vs. 3.0 months; hazard ratio [HR]=0.47, 95% CI: 0.33-0.67; p<0.001) and median OS (9.5 vs. 6.4 months; HR = 0.51, 95% CI: 0.34-0.77; p=0.0012) compared to the non-CIBP group. The survival benefit of CIBP remained robust after multivariable adjustment (PFS HR = 0.54, p=0.003; OS HR = 0.65, p=0.044) and propensity score matching. Subgroup analyses revealed that patients with PD-L1 expression ≥1%, those who achieved an objective response to first-line therapy, or those with a first-line PFS ≥6 months derived the greatest benefit from CIBP. The safety profile was manageable and comparable between the two groups.

In this real-world cohort, continuing ICI beyond progression was associated with significantly superior survival outcomes compared to switching to non-ICI regimens, with a manageable safety profile. CIBP represents a valid and promising second-line strategy for selected patients with advanced GC/GEJC following first-line immuno-chemotherapy failure.