Clinical Characteristics and Molecular Patterns of <i>RET</i>-Rearranged Lung Cancer in Chinese Patients

Abstract

<i>RET</i> rearrangement has been proven as an oncogenic driver in patients with lung cancer. However, the prevalence, clinical characteristics, molecular features, and therapeutic options in <i>RET</i>-rearranged patients remain unclear, especially in Chinese lung cancer patients. We retrospectively collected 6,125 Chinese lung cancer patients who have been profiled using next-generation sequencing (NGS). The clinical demographics and molecular features of <i>RET</i> rearrangement-positive patients were analyzed. <i>RET</i> rearrangements were identified in 84 patients with a proportion of 1.4% in our cohort. The median age at diagnosis was 58 years, and it mainly occurred in females with adenocarcinoma histology. <i>KIF5B-RET</i> was the most frequent fusion type and accounted for 53.8% (57/106) of all <i>RET</i> fusions identified, with K15-R12 as the most frequent variant (71.9%). Among 47 <i>RET</i>⁺ patients profiled with larger panels, 72.3% (34/47) harbored concurrent alterations. <i>TP53</i> ranked as the most common concurrent alteration, and concomitant <i>EGFR</i> oncogenic alterations were identified in seven patients. Moreover, an adenocarcinoma patient harboring concurrent <i>RET</i> fusion and <i>EGFR</i> L858R responded to combinatorial treatment of cabozantinib and osimertinib, with a progression-free survival of 5 months. Our study improved knowledge of clinical characteristics and molecular features of <i>RET</i>-rearranged lung cancers in China. It might be helpful to guide clinicians for more effective personalized diagnostic and therapeutic approaches.