Use of RET inhibitors among patients with advanced NSCLC: A real-world evidence analysis.

9079 Background: RET rearrangements are found in approximately 1% to 2% of patients with NSCLC. Two selective RET inhibitors have been FDA approved based on phase 1/2 data showing significant activity among patients with advanced NSCLC that have RETrearrangements. The objective of this retrospective analysis was to look at the prognostic outcome associated with the use of selective RET inhibitors (sRETi) and multikinase inhibitors (MKIs) that have been used to target RET fusions among pts with NSCLC in the real-world setting. Methods: We utilized a federated network of de-identified health data representing approximately 84 million pt lives available through the TriNetX Research Network. We identified 1,215 pts with metastatic NSCLC treated with selpercatinib, praseltinib, cabozantanib or vandetanib. Overall survival (OS) was evaluated with Kaplan Meier statistics and compared between patients treated with either sRETi (selpercatinib or pralsetinib) vs either MKI (cabozantanib or vandetanib). Results: Mean age among all anti-RET treated patients was 67.6 years. 518 pts (43%) were female and 697 (57%) were male. 531 (39.6%), 205 (15.3%) and 605 (45.1%) pts had received selpercatinib, pralsetinib, and either cabozantinib or vandetinib, respectively. 56.6% of pts receiving pralsetinib received prior selpercatinib. Among pts receiving sRETi, 39.7%, 6.4%, 11.2%, and 32.4% received sRETi in the 0-3, 3-6, 6-12, and 12+ months after metastatic diagnosis, respectively. Among pts receiving MKIs, 17.0%, 8.4%, 13.3%, and 44.9% received MKIs in the 0-3, 3-6, 6-12, and 12+ months after metastatic diagnosis. Median OS after treatment with MKIs and sRETi during any time frame was 16.3m and 25.0m, respectively (p < 0.01). Among pts treated with MKIs vs sRETi during the 0-3, 3-6, 6-12, and 12+ months after metastatic diagnosis, 1-year survival probability after treatment was 59.7% vs 55.9% (p = 0.39), 45.0% vs 83.1% (p < 0.01), 53.9% vs 82.2% (p < 0.01), and 57.7% vs 87.1% (p < 0.01), respectively. 30% of pts of all anti-RET treated patients had brain metastases, and median OS from index metastasis among pts with and without brain metastases was 31.4m and 63.1m respectively (p < 0.01). Conclusions: To our knowledge this is the first real world data set to show a > 8m improvement in OS with the use of sRETi compared to MKIs among pts with metastatic NSCLC. OS improvements may be more significant in pts treated in later lines of therapy with sRETi.