Survival Outcomes With Cadonilimab Versus PD-(L)1 Therapy in Front-Line Gastric Cancer: A Network Meta-Analysis.
The FDA Oncologic Drugs Advisory Committee (ODAC) highlighted that the risk-benefit profile for patients with low PD-L1 expression remains unclear in front-line treatment of HER2-negative gastric and gastroesophageal junction (GC/GEJ) cancer with PD-(L)1 therapy. The first PD-1/CTLA-4 bispecific antibody (BsAb), cadonilimab, has been approved, but it is unknown if it can extend the PD-(L)1 regimen to lower PD-L1 patients.
To indirectly compare the survival outcomes of cadonilimab versus PD-(L)1 therapy in first-line HER2-negative gastric and gastroesophageal junction cancer, with particular focus on patients with low PD-L1 expression, using a network meta-analysis.
Randomized controlled trials with ICIs as first-line treatment were searched in public databases and FDA ODAC up to December 31, 2024. A network meta-analysis was conducted to evaluate the efficacy and safety of approved ICI-based treatments to refine the optimal approach for front-line GC/GEJ.
A total of 7127 patients from eight Phase III trials were included. All ICIs-based therapies significantly improved overall survival (OS) compared to chemotherapy. In indirect comparisons, cadonilimab plus XELOX was associated with numerically more favorable OS (HR = 0.78, 95% CI: 0.62-0.98) compared with PD-(L)1 inhibitors. Numerical trends toward longer survival were observed across subgroups, including patients with PD-L1 < 10 (HR = 0.77, 95% CI: 0.58-1.01) and liver metastasis (HR = 0.67, 95% CI: 0.49-0.93), both historically considered immunotherapy-insensitive populations. All ICIs improved PFS compared to chemotherapy. Cadonilimab was associated with numerically better PFS versus PD-(L)1 inhibitors in indirect comparisons (HR = 0.70, 95% CI: 0.57-0.86). The safety analysis showed no significant increase in severe adverse events.
In this indirect comparison, cadonilimab showed more favorable survival outcomes versus PD-(L)1 inhibitors in first-line GC/GEJ. Subgroup benefits were observed in liver metastasis, while the PD-L1 < 10 subgroup showed numerical trends. These results highlight the importance of selecting appropriate ICIs to optimize outcomes.
To indirectly compare the survival outcomes of cadonilimab versus PD-(L)1 therapy in first-line HER2-negative gastric and gastroesophageal junction cancer, with particular focus on patients with low PD-L1 expression, using a network meta-analysis.
Randomized controlled trials with ICIs as first-line treatment were searched in public databases and FDA ODAC up to December 31, 2024. A network meta-analysis was conducted to evaluate the efficacy and safety of approved ICI-based treatments to refine the optimal approach for front-line GC/GEJ.
A total of 7127 patients from eight Phase III trials were included. All ICIs-based therapies significantly improved overall survival (OS) compared to chemotherapy. In indirect comparisons, cadonilimab plus XELOX was associated with numerically more favorable OS (HR = 0.78, 95% CI: 0.62-0.98) compared with PD-(L)1 inhibitors. Numerical trends toward longer survival were observed across subgroups, including patients with PD-L1 < 10 (HR = 0.77, 95% CI: 0.58-1.01) and liver metastasis (HR = 0.67, 95% CI: 0.49-0.93), both historically considered immunotherapy-insensitive populations. All ICIs improved PFS compared to chemotherapy. Cadonilimab was associated with numerically better PFS versus PD-(L)1 inhibitors in indirect comparisons (HR = 0.70, 95% CI: 0.57-0.86). The safety analysis showed no significant increase in severe adverse events.
In this indirect comparison, cadonilimab showed more favorable survival outcomes versus PD-(L)1 inhibitors in first-line GC/GEJ. Subgroup benefits were observed in liver metastasis, while the PD-L1 < 10 subgroup showed numerical trends. These results highlight the importance of selecting appropriate ICIs to optimize outcomes.
Authors
Yu Yu, Yi Yi, Xue Xue, Huang Huang, Zhao Zhao, Jiang Jiang, Yin Yin, Xia Xia, Zhou Zhou, He He, Xia Xia
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