Development and validation of a new tool to estimate early mortality in patients with advanced cancer treated with immunotherapy

Abstract Background: Immune checkpoint inhibitors (ICIs) are standard treatments for advanced solid cancers. Resistance to ICIs, both primary and secondary, poses challenges, with early mortality (EM) within 30–90 days indicating a lack of benefit. Prognostic factors for EM, including the Lung Immune Prognostic Index (LIPI), remain underexplored. Methods: We performed a retrospective, observational study including patients affected by advanced solid tumors, treated with ICI as single-agent or combined with other agents. Logistic regression models identified factors associated with EM and 90-day progression risks. A nomogram for predicting 90-day mortality was built and validated within an external cohort . Results: 637 patients received ICIs (single-agent or in combination with other drugs) for advanced solid tumors. Most patients were male (61.9%), with NSCLC as the prevalent tumor (61.8%). Within the cohort, 21.3% died within 90 days, 8.4% died within 30 days, and 34.5% experienced early progression. Factors independently associated with 90-day mortality included ECOG PS 2 and a high/intermediate LIPI score. For 30-day mortality, lung metastasis and a high/intermediate LIPI score were independent risk factors. Regarding early progression, high/intermediate LIPI score was independently associated. A predictive nomogram for 90-day mortality combining LIPI and ECOG PS achieved an AUC of 0.76 (95% CI, 0.71–0.81). The discrimination ability of the nomogram was confirmed in the external validation cohort (n = 255) (AUC 0.72,95% CI, 0.64–0.80). Conclusion: LIPI and ECOG PS independently were able to estimate 90-day mortality, with LIPI also demonstrating prognostic validity for 30-day mortality and early progression.