Genomic Profiling of Driver Gene Alterations in Patients With Non-Small Cell Lung Cancer, Patterns of Treatment and Impact on Survival Outcomes: A Single Center Experience of More Than 1200 Patients

Abstract

Background: The utility of Next-Generation-Sequencing (NGS) in patients of non-small-cell-lung-cancer (NSCLC) has led to an exponential increase in the identification of driver-gene alterations, however, Indian NGS data was lacking.

Materials and methods: This retrospective study conducted between May'2019 and Dec'2023 included histologically confirmed NSCLC cases with NGS testing done on tissue and/or liquid biopsy samples prior to treatment initiation. We reported the frequency of driver-gene alterations, clinicopathological profile, treatment patterns, and outcomes [Overall-Survival (OS)].

Results: Data of 1230 patients was analyzed. Median age was 59 years (IQR,51-66), 65.3% (n = 803) were males, 34.6% (n = 426) had a history of smoking, and 78.1% (n = 961) had an adenocarcinoma histology. NCCN-recommended driver-gene alterations were seen in 64.8% (n = 797) cases. EGFR, ALK, ROS1, ERBB2, MET, RET, NTRK, BRAF and KRAS gene alterations were seen in 33.7% (n = 414), 7.6% (n = 94), 2.4% (n = 29), 6.1% (n = 75), 1.9% (n = 23), 2.2% (n = 22), 0.7% (n = 8), 3.3% (n = 40), and 9.6% (n = 118) cases respectively. 62.1% (n = 495/797) driver-positive patients could receive targeted therapy, and 21.7% (n = 94/433) driver-negative patients could receive immunotherapy. With the receipt of targeted therapy, median-OS of driver-positive patients was 26.7 months (95%CI, 23.3-32.7) versus 9.3 months (95%CI, 7.3-12.2, P < .001) without. Similarly, in driver-negative patients, median OS with the receipt of immunotherapy was 16.4months (95%CI, 14.7-24.4) versus 11.5 months (95%CI, 9.0-13.4, P = .006) without.

Conclusion: All eligible NSCLC patients must undergo molecular testing by appropriately chosen and cost-effective methods at diagnosis. Wherever possible, this should be done by NGS. Efforts should focus on improving access to targeted agents in India, and developing cost-effective alternatives.

Keywords: Driver genes; Immunotherapy; NSCLC; Next generation sequencing; Targeted therapy.