Impact of Small-Scale ROS1 Mutations on Survival, Treatment Efficacy in NSCLC

By Mary Grecco - Last Updated: January 31, 2024

The results of a study that analyzed the clinicopathological characteristics of small-scale ROS1 mutations in patients with NSCLC and the impact on survival and response to systemic therapy were presented at the ESMO Congress 2023.

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The researchers performed next-generation sequencing on tissue samples from patients with NSCLC within the Network Genomic Medicine collaborative, excluding patients with ROS1 fusions and solvent front mutations. Results showed that among 10,396 patients analyzed, 101 (1%) harbored small-scale ROS1 mutations. Most patients were males (73.3%) who were smokers (96.6%). Almost half of the patients presented with squamous cell carcinoma (40.4%). Most mutations were transversions (50.5%) and 66.0% were in the kinase domain. In addition to TP53 mutations (65.3%), KRAS (22.8%), EGFR (5.9%), PIK3CA (9.9%), and FGFR1-4 mutations (8.9%) co-occurred. In 10 patients (9.9%), ROS1 mutation was the only aberration detected.

The researchers found that median overall survival of all stage IV patients was 10.5 months and that survival differed significantly in patients with or without KRAS co-mutations (9.7 vs 21.5 months; hazard ratio, 2.6; 95% CI; 1.1-5.9; P=.02). Although not significant, the most common KRAS mutation in this cohort, G12V (n=7/17), worsened survival (4.4 vs 9.7 months).

The researchers concluded that co-occurrence of KRAS mutations led to shortened survival and patients benefited from immune checkpoint blockade; however, they noted their “data do not support the idea of ROS1 small-scale mutations as strong oncogenic drivers in NSCLC, but rather as relevant bystanders altering the efficacy of treatment approaches.”

Source: Glaser M, Braegelmann S, Rasokat A, et al. Survival and therapy analysis of small-scale ROS1-mutant non-small cell lung cancer (NSCLC) patients. Abstract of a poster presented at the ESMO Congress 2023; October 20-24, 2023; Madrid, Spain.

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