Chemotherapy backbone and outcomes of immune checkpoint inhibitor combinations across solid tumors: a pan-tumor network meta-analysis

Abstract

Abstract 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 vs 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 Tables S1-S6. Chemo–immunotherapy significantly improved progression-free survival (hazard ratio [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.