Biomarker testing in non-small cell lung carcinoma – More is better: A case series

Abstract

Background: Biomarker-driven lung adenocarcinomas involving alterations in oncogenic drivers such as EGFR, ALK, ROS1, and NTRK have witnessed a dramatic shift in the therapeutic and prognostic landscape owing to the development of molecular targeted therapies. The recent approval of the selective RET inhibitor, selpercatinib, has led to an ardent interest in RET-rearranged non-small cell lung carcinoma (NSCLC). However, sequential single-gene testing cannot detect RET rearrangements accurately or characterize the fusion partners. Objectives: We aimed to determine the incidence and types of RET alterations in our patients with NSCLC, and to describe the demographic and clinical profile of our patients with RET-driven NSCLC. In addition, our aim was to highlight the advantages of broader panel-based testing by the next generation sequencing (NGS) over single-gene assays. Materials and Methods: This is a retrospective, case series of patients with advanced NSCLC who underwent testing by NGS between December 2018 and August 2020 at our center, with a focus on the cases who were found to have the RET gene rearrangement. The demographic, clinicopathological profiles, and treatment details were retrieved from the medical record archives. Statistical analysis was performed using the Statistical Package for the Social Sciences software version 23 for Windows. Results: A total of 169 patients were enrolled in the study. RET rearrangement was detected in 2.9% (n = 5) of the patients in our cohort. Four cases had the KIF5B-RET fusion, and one case had the CCDC6-RET fusion. The median age of the patients was 55 years (range, 45–82), with a slight female preponderance (men: 2 and women: 3). The RET fusions were detected using an NGS-based assay. Four out of the five patients were administered pemetrexed-carboplatin-based chemotherapy and are alive and on regular follow-up. One patient did not receive any treatment and has succumbed to the disease. One patient has been administered selpercatinib after failing many lines of chemotherapy. Conclusions: The emergence of newer molecular targets necessitates the use of an broader panel-based NGS testing to detect oncogene addiction in NSCLC. This case series highlights the importance of NGS-based testing in the light of the recent approval of selpercatinib for RET-rearranged NSCLC.