Reduced risk of secondary primary extra pulmonary cancer in advanced/metastatic lung cancer patients treated with immune checkpoint inhibitors

Abstract

BackgroundLung cancer survivors are at high risk of developing a second primary cancer (SPC). We explored the Unicancer Epidemiology Strategy Medical-Economics for advanced or metastatic lung cancer (AMLC) database to assess the impact of immune checkpoint inhibitors (ICI) on the risk of SPC in patients with advanced/metastatic lung cancer. Patients and methodsThis retrospective study used data from patients with AMLC, with treatment initiated between January 1st 2015 and December 31st 2018. Patients with lung cancer as the second primary cancer were excluded and a 6-months landmark threshold was applied to exclude patients with synchronous SPC, patients dead without SPC or with a follow-up inferior to 6 months. A propensity score (PS) was calculated on the following baseline covariates: Age at locally advanced or metastatic diagnosis, sex, smoking status, metastatic status, performance status and histological type. The inverse probability of treatment weighting approach was used on the analyses aiming to assess the impact of ICI administered for AMLC, on the risk of occurrence of SPC. ResultsAmong the 10 796 patients, 148 (1.4%) patients had a diagnosis of SPC in a median interval of 22 (min–max: 7–173) months. All the patients (100%) with locally advanced or metastatic LC received at least one systemic treatment including (chemotherapy regimen (n = 9 851, 91.2%); ICI (n = 4 648, 43.0%); targeted treatment (n = 3 500; 32.4%). 40 (0.9%) SPC were reported in the 4 648 patients with metastatic LC treated with ICI vs 108 (1.7%) out of the 6 148 who did not receive immunotherapy (p < 0.0001). The multivariate analysis identified that treatment with ICI in patients with AMLC is associated with a reduced risk of SPC (HR = 0.40, 95% CI 0.27–0.58). ConclusionTreatment with ICI in AMLC patients was associated with a significantly reduced risk of SPC. Prospective studies are required to confirm these results.