Syst-16 propensity-matched survival analysis of second and third generation tyrosine kinase inhibitors in the treatment of brain metastases from lung cancer primary

Abstract INTRODUCTION Brain metastases from lung cancer (BMLC) are common and represent an aggressive form of disease. Numerous ongoing clinical trials are investigating targeted molecular therapies against epidermal growth factor receptor (EGFR), which have demonstrated blood-brain-barrier permeability and intracranial activity. However, there is limited real-world efficacy data on second and third-generation EGFR tyrosine kinase inhibitors (TKI), Afatinib and Osimertinib, for the treatment of BMLC. This study provides a real-world assessment to evaluate the impact of these agents on overall survival (OS) at the population-level. METHODS This retrospective cohort study queried data from TriNetX, a multi-institutional de-identified database, aggregating data from 90 U.S. healthcare organizations. Three cohorts were established, consisting of patients with BMLC treated with 1) Osimertinib, 2) Afatinib, or 3) Neither Osimertinib nor Afatinib. Cohorts 1 and 3, as well as cohorts 2 and 3, were propensity matched on demographics and comorbidities. Median overall survival (OS) was compared via Kaplan Meier analyses, using log-rank tests and Cox proportional hazards ratios (HR). RESULTS After matching, we identified 1,990 BMLC patients treated with Osimertinib (cohort 1) and 1,990 treated without Afatinib and Osimertinib (cohort 3). Median OS was 21.2 months and 13.5 months for the two cohorts, respectively (p < 0.0001; HR [95% CI], 0.69 [0.63-0.77]). Furthermore, we identified 685 BMLC patients treated with Afatinib (cohort 2) and 685 treated without Afatinib and Osimertinib (cohort 3) after matching. Median OS was 19.0 months and 11.5 months, respectively (p < 0.0185; HR [95% CI], 0.83 [0.71-0.97]). CONCLUSION Afatinib and Osimertinib demonstrated a significant survival benefit for patients with BMLC, with comparable, if not better, results to other therapeutic options. These findings suggest strong intracranial efficacy of these agents, while indicating a greater generalizability of the results. Further prospective studies are warranted to better understand their potential role in the BMLC treatment paradigm.