Chemotherapy Backbone and Outcomes of Immune Checkpoint Inhibitor Combinations Across Solid Tumors: A Pan-Tumor Network Meta-Analysis

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BACKGROUND: Immune checkpoint inhibitors (ICIs) combined with chemotherapy represent a first-line standard across multiple solid tumors; however, the contribution of chemotherapy backbone to the efficacy of chemo-immunotherapy remains uncertain. METHODS: We conducted a systematic review and network meta-analysis of phase II-III randomized trials comparing ICI-chemotherapy versus chemotherapy alone, with the aim of evaluating whether chemotherapy backbone selection was associated with differences in clinical outcomes across tumor types. RESULTS: Thirty-nine trials including over 30,000 patients were analyzed. Detailed characteristics of included trials by tumor type are reported in Supplementary Tables S1-S6. Chemo-immunotherapy significantly improved progression-free survival (HR 0.69, 95% CI 0.66-0.72) and overall survival (HR 0.78, 95% CI 0.76-0.81). Among the evaluated chemotherapy backbones, platinum-pemetrexed was associated with the greatest relative survival benefit (HR 0.66), followed by platinum-taxane and fluoropyrimidine-platinum regimens (HR 0.78), whereas platinum-gemcitabine showed comparatively lower benefit (HR 0.83). Anti-PD-1 regimens demonstrated numerically greater benefit than anti-PD-L1 therapies, although these findings should be interpreted in light of the non-random distribution of treatment regimens across tumor types. Because chemotherapy backbones were closely linked to tumor-specific standards of care, these differences cannot be interpreted as evidence of superiority across tumor types. All combinations increased grade ≥3 adverse events. CONCLUSION: Differences in outcomes were observed across chemotherapy backbones; however, these findings likely reflect the combined influence of tumor-specific treatment paradigms, underlying disease biology, and potentially the chemotherapy backbone itself. Therefore, the results should be considered hypothesis-generating and warrant prospective validation within individual tumor types.

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