Clinical outcomes between patients with and without RET fusions in advanced/metastatic non-small cell lung cancer in the United States.

Abstract

e21693 Background: Fusions involving the REarranged during Transfection ( RET) gene are known oncogenic drivers in non-small cell lung cancer (NSCLC). The patient profile is distinct from a genomically-unselected population of NSCLC patients and may lead to the potentially confounded conclusion that RET fusion-positive patients have a better prognosis. This study characterized clinical outcomes in patients with RET fusion-positive NSCLC versus those without when correcting for known demographic differences. Methods: The Flatiron ClinicoGenomics Database, electronic medical record data linked to Foundation Medicine, Inc genomic test results, was used to identify individuals diagnosed with advanced or metastatic NSCLC who initiated anti-cancer systemic therapy between JAN2011 and JUN2019 in the US. Follow up data were available through JUN2019. Patients were considered RET+ if a fusion was reported and RET- if no fusion was reported. Baseline characteristics and tumor response were compared using Fisher’s exact, chi-squared or t-tests; unadjusted and adjusted COX models were used to compare progression-free survival (PFS) and overall survival (OS). Results: There were 5,807 eligible patients with NSCLC; 46 (0.8%) and 5,761 (99.2%) were RET+ and RET-, respectively. Patients with RET+ tumors were significantly younger (63 vs 67 yrs), better performance status, less likely to have smoking history (37% vs 82%), more likely to have non-squamous tumors (98% vs 76%) (all p < 0.05), and less likely to have ALK, ROS1, KRAS or BRAF alterations, which were each 0% in the RET+ group. There were no differences in total lines of therapy received; treatment regimens were comparable. In unadjusted analyses, patients with RET+ tumors had no significant differences in tumor response (p = 0.17) or PFS (p = 0.06) but significantly better OS outcomes (p = 0.005) from the start of first-line therapy. After adjusting for all available baseline covariates, survival outcomes were not significantly different between RET- and RET+ groups (PFS hazard ratio [HR] = 1.24, 95% confidence interval [CI] = 0.86, 1.78, p = 0.26; OS HR = 1.53, 95% CI = 0.95, 2.44, p = 0.08). Conclusions: Patients with RET fusion-positive NSCLC have different baseline characteristics than patients without these fusions. The unadjusted differences in OS between groups appear to be driven by baseline demographic features and not the presence of the RET fusion, however further research is needed. Conclusions are limited by the rarity of RET fusions in NSCLC and subsequent small sample size.