The clinical significance of RET gene fusion among Chinese patients with lung cancer

Abstract

Background: The incidence of lung cancer is growing fast in China, however, the prognosis remains dismal due to the limited therapeutic approaches. The “ret proto-oncogene mutation” (RET) fusions have been proven to be the driver gene in lung cancer development and the therapeutic target of several multi-target tyrosine kinase inhibitors. Methods: We applied formalin-fixed, paraffin-embedded (FFPE) samples of 39 patients with non-small cell lung cancer (NSCLC) using the Lung Plasma panel covering 168 cancer-associated genes and performed capture-based targeted deep sequencing to identify the RET fusion partners and concurrent gene mutation with Miseq. The log-rank test was used to compare the survival difference of patients according to treatment strategies. Statistical analyses and graphs were performed using R language and GraphPad Prism. Results: Most of the samples were advanced (stage IIIb and IV) lung adenocarcinomas (80.77%). KIF5BRET fusions were identified in 52% of the samples and K15-E12 was the most common variant. 6 (15%) samples harbored concurrent TP53 mutation and 3 samples were positive with EGFR mutation including a mutation in exon 19. Of these patients included, ten received cabozantinib, two received anlotinib, and one received crizotinib. Two (20%; 0-45) samples achieved stable disease and two were progressed in the cabozantinib treated group. Median progression-free survival (PFS) was 4 months (95% CI: 3.2-4.8) and median overall survival (OS) was 25 months (95% CI: 1.5-48.5). Three (11.54%; 0-24) samples achieved partial response in patients without RET inhibitor treatment and 4 (15.38%; 2-29) were stable disease. The median PFS was 11 months (95% CI: 1.2-20.8). There was no significant difference in PFS and OS between groups with or without RET inhibitors treatment. Conclusion: This study provided insight into the RET fusions patients treatment. The survival benefit of current RET inhibitors was limited. More precise and potent RET inhibitors should be developed in the near future.