Osimertinib versus first/second generation tyrosine kinase inhibitors as first-line therapy for metastatic EGFR-mutated non-small cell lung carcinoma: Overall survival using real-world data from TriNetX platform

BackgroundOsimertinib (Osi) is the standard first line for advanced non-small cell lung carcinoma (NSCLC) harboring EGFR exon 19 deletion or L858R mutation. After approval by regulatory authorities, only small size studies with real world data (RWD) comparing Osi with first and second generation tyrosin kynase inhibitors (TKI) have been published. Here we present overall survival (OS) analysis of a big cohort of patients treated with Osi or 1st/2nd generation TKIs (oTKI) as first line therapy for EGFR-mutated NSCLC.MethodsUsing TriNetX Global Collaborative Network we identified patients with metastatic/advanced NSCLC from 77 healthcare organizations treated with TKIs (osimertinib, gefitinib, erlotinib, dacomitinib or afatinib) as first line systemic therapy. Treatment start happened between January 2014 and December 2021. Propensity score matching (PSM) was used to balance cohorts on age, gender and race. Kaplan-Meier analysis was used to compare the 5-year overall survival (OS) between the cohorts.ResultsWe identified 7643 patients (3176 treated with Osi, 4467 with oTKI). Median follow up was 763 days for patients treated with Osi and 705 days for oTKI. Mean age was 66 versus 65 years (p=0.058), female proportion was 65.8 vs 60.8% (p<0.001), and Asian population proportion was 17.9 vs 21.1% (p=0.001) for Osi and oTKI group respectively. Using raw data, OS was significantly better for Osi (mOS 1095 days) versus oTKI (mOS 826 days), with HR 0.79 (95% CI 0.74-0.84, p<0.001). After matching cohorts by age, sex, and race OS benefit was keeped for Osi with HR 0.80 (95% CI 0.75-0.86, p<0.001).ConclusionsThis is the biggest RWD analysis of OS for first line treatment of EGFR-mutated NSCLC. Osimertinib improves OS compares to other TKIs, even after matching cohorts by age, sex, and race.Legal entity responsible for the studyThe authors.FundingHas not received any funding.DisclosureAll authors have declared no conflicts of interest.