P87.04 Chemotherapy and Immunotherapy Outcomes of RET-Rearranged Lung Cancers: A Case Series

Abstract

RET rearrangement is detected in 1% to 2% of lung adenocarcinomas. RET fusions correlate with adenocarcinoma histologic subtype, never-smoking status, younger age, more advanced disease stage. Prior studies have reported potential higher chemosensitivity and low response to immunotherapy. Given the rarity of these tumors, the natural history, and the role of chemotherapy and immunotherapy in the context of new selective RET inhibitors is still being defined. We performed a retrospective review of RET-rearranged lung cancer cases treated at the University of Miami from 2013 to 2020. RET rearrangements were identified using targeted next-generation sequencing of DNA (FoundationOne or Caris). Clinicopathologic characteristics and response to chemotherapy and immunotherapy were analyzed. PFS was defined as the time from therapy initiation to radiologic progression or death. Overall survival (OS) was defined as time from diagnosis of metastatic disease to death. For PFS, and OS analyses, Kaplan-Meier curves were compared using the Mantel-Cox log-rank test. A total of 15 patients with a median age of 64 (range 50-83) were identified in a cohort of 617 sequenced lung cancers (representing a prevalence of 2.4%). There were 9 women; 11 never smokers; 1 light smoker (<1pack/day) and 3 former smokers (>1pack/day). The patients came from a diverse background (7 Non-Hispanic whites, 5 Hispanics, 1 Asian, 2 African Americans). The majority of cases had adenocarcinoma histology and KIF5B-RET fusions (n=14)). In 10 patients with sufficient tissue for PD-L1testing, PD-L1 expression was 0%, low (1-49%), and high (50% or greater) in 50% (n=5 of 10), 10% (n=1 of 10), and 40% (n=4 of 10) of cases, respectively. Twelve patients (80%) presented with metastatic disease and three (20%) with locally advanced disease. The most common sites of metastases were lung (15), followed by bone (10), brain (6), malignant pleural effusion (6), and liver (3). The median overall survival was 33 months (range 6 to 87). Five out of six patients with malignant pleural effusion had prolonged survival greater than 32 months. Eleven patients received platinum-based chemotherapy and 7 patients received immunotherapy during their course of treatment. Nine patients who received platinum-pemetrexed chemotherapy in the first line setting had prolonged responses with a median PFS of 19 months (range 5-53 mos), while those who received immunotherapy (n=6) had lower median PFS of 9 months (range 4-13 mos). Three patients with tumors that showed high PDL1 expression responded to immunotherapy for an average of 10 months. RET-rearranged lung cancer in our series presented with adenocarcinoma, never smoking status, younger age and advanced disease. PFS after treatment with pemetrexed based chemotherapy in RET cases was longer than after immunotherapy. However, no patients in this series received combination chemotherapy and immunotherapy which is currently a standard of care. Unlike prior reports, patients with RET arranged lung cancers and high PDL1 expression responded to immunotherapy in this series. More data is needed to define the role of chemotherapy and immunotherapy in the context of new selective RET inhibitors.