58P - NSCLC genomic complexity: Insights from comprehensive molecular profiling in the era of precision medicine

Background

Non-small cell lung cancer (NSCLC) accounts for 5.9% of all cancers in India and is responsible for 8.1% of all cancer-related mortality. The National Comprehensive Cancer Network (NCCN) reports that 5-year survival rates for NSCLC vary widely, from 15% to 62.5%, depending on specific biomarkers. Therefore, biomarker testing is crucial to guide treatment selection and improve outcomes for patients with NSCLC.

Methods

A total of 108 NSCLC cases were studied, including 66 males and 42 females. Next-generation sequencing (NGS) using a 50-gene panel was performed for all cases. Additionally, fluorescence in situ hybridization (FISH) tests were conducted for ALK, ROS1, and MET genes, and immunohistochemistry (IHC) was used to assess PD-L1 status.

Results

The overall age range of patients was 26-84 years, with the majority aged 55-65. NGS results were obtained for 55 cases. EGFR mutations were identified in 20 patients (10 males and 10 females), with exon 19 deletion being the most common mutation (13 patients). TP53 mutations were found in 16 patients, with 5 having only TP53 mutations and the rest having concurrent driver gene mutations. KRAS mutations were found in 9 patients (4 males and 5 females) with 3 of these having another gene mutation. No mutations were identified in 29 patients. ALK gene rearrangements were present in 2 cases, ROS1 rearrangements in 2 cases, and MET gene amplification in 1 patient. PD-L1 was positive in 19 cases, with >50% expression in 4 cases. Among these 4, one had a RET mutation, and another had ERBB2 gene duplication. Importantly, eight cases had mutations in three or more genes, indicating that concurrent genetic alterations are common.

Conclusions

This study highlights the importance of comprehensive molecular profiling in NSCLC, revealing multiple gene alterations within individual patients. A variety of actionable and non-actionable mutations were identified, underscoring the genomic complexity of NSCLC. These findings emphasize the need for further research to understand the impact of multiple concurrent mutations on disease progression and treatment response, and to develop targeted therapies for these unique genetic profiles.

Editorial acknowledgement

Clinical trial identification

Legal entity responsible for the study

Oncquest Laboratories Limited.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.