Real-World Evidence from the TriNetX Network: Assessing Immunotherapy's Impact on Second Primary Cancer Risk in Metastatic Lung Cancer (Preprint)

BACKGROUND Lung cancer survivors are at high risk of developing a second primary cancer (SPC). This study investigated the impact of immune checkpoint inhibitors (ICIs) on the risk to develop a SPC in a large cohort of metastatic lung cancer patients. OBJECTIVE This study investigated the impact of immune checkpoint inhibitors (ICIs) on the risk to develop a SPC in a large cohort of metastatic lung cancer patients. METHODS Using a retrospective cohort from the TriNetX Global Collaborative research network, the study analyzed the incidence of SPC in metastatic lung cancer (MLC) patients treated with ICIs against those who were not. Propensity score matching and Kaplan-Meier to assess the effect of ICIs on the development of SPCs. RESULTS The study analyzed 2,844 MLC patients, with 685 receiving ICIs and 2,157 not receiving ICIs. Post-propensity score matching, each cohort included 685 patients. The 5-year analysis revealed a lower incidence of SPCs in the ICI group (1.5%) compared to the non-ICI group (4.2%), with a Hazard Ratio (HR) of 0.49 (95%CI [0.24-1.01]) indicating a reduced risk. Treatment with ICIs was associated with a significant risk reduction of SPC or death (HR=0.78; 95%CI [0.62-0.89]). CONCLUSIONS ICIs reduce the risk of SPCs in metastatic lung cancer patients. Despite limitations, the study confirms the preventive role of ICIs and the importance of real-world data to identify novel paradigm changing strategies. CLINICALTRIAL Not applicable