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Background  Contradictory and limited data are available about the presentation and outcomes of patients with  RET -fusion positive metastatic NSCLC as compared to patients without  RET  fusions. This observational study utilizing a linked electronic health records (EHR) database to genomics testing results was designed to compare characteristics, tumor response, progression-free (PFS) and overall survival (OS) outcomes by  RET  fusion status among patients with metastatic NSCLC treated with standard therapies.    Methods  Adult patients with metastatic NSCLC with linked EHR and genomics data were eligible who received systemic anti-cancer therapy on or after January 1, 2011. Adjusted, using all available baseline covariates, and unadjusted analyses were conducted to compare tumor response, PFS and OS between patients with  RET- fusion positive and  RET -fusion negative disease as detected by next-generation sequencing. Tumor response outcomes were analysed using Fisher’s exact test, and time-to-event analyses were conducted using Cox proportional hazards model.    Results  There were 5807 eligible patients identified ( RET + cohort,  N  = 46;  RET - cohort,  N  = 5761). Patients with  RET  fusions were younger, more likely to have non-squamous disease and be non-smokers and had better performance status (all  p  < 0.01). In unadjusted analyses, there were no significant differences in tumor response ( p  = 0.17) or PFS ( p  = 0.06) but OS was significantly different by  RET  status (hazard ratio, HR = 1.91, 95% CI:1.22–3.0,  p  = 0.005). There were no statistically significant differences by  RET  fusion status in adjusted analyses of either PFS or OS (PFS HR = 1.24, 95% CI:0.86–1.78,  p  = 0.25; OS HR = 1.52, 95% CI: 0.95–2.43,  p  = 0.08).    Conclusions  Patients with  RET  fusions have different baseline characteristics that contribute to favorable OS in unadjusted analysis. However, after adjusting for baseline covariates, there were no significant differences in either OS or PFS by  RET  status among patients treated with standard therapy prior to the availability of selective  RET  inhibitors.

Characteristics and outcomes of patients with RET-fusion positive non-small lung cancer in real-world practice in the United States