Co-mutations in non small cell lung cancer: Real-world data and clinical insights from a tertiary care centre in western India.

e20689 Background: The management of non-small cell lung cancer (NSCLC) has advanced with molecular profiling and targeted therapies. However, complex cases with multiple coexisting mutations pose significant therapeutic challenges. This study shares our experience managing such cases at a tertiary care center in Western India. Methods: This retrospective study was conducted at the Medical Oncology/Haematology Department of AIIMS, Jodhpur, India, on lung carcinoma patients treated between September 2023 and December 2024, excluding small cell lung carcinoma. Data was retrieved from the Hospital Information System (HIS). Molecular profiling was done using a 12-gene next-generation sequencing panel, with ALK and ROS1 tested by IHC or RT-PCR, and PD-L1 expression assessed using Ventana SP263 antibody. Results: A total of 266 lung carcinoma patients were registered during the study period, with molecular profiling performed on 72 (27%) of them. Among these, 49 (68%) were male, 23 (32%) were female, with a mean age of 59 years. Pathogenic driver mutations were identified in 47 (65.2%) patients, of which 28 (38.9%) had one mutation and 19 (26.4%) had more than one mutation. Two patients (2.8%) had over two mutations. Table 1 presents the distribution of pathogenic mutations in NSCLC patients (N = 72). EGFR-mutant patients treated with chemotherapy plus first-generation TKIs achieved a PFS of 13 months, versus 8 months with chemotherapy alone. ALK and ROS1 co-mutation patients received either chemotherapy or Lorlatinib. Conclusions: With the evolving diagnostic and therapeutic paradigm of lung cancer, multiple coexisting mutations present a new therapeutic challenge, highlighting the emergent need for improved strategies to address these clinical issues. Distribution of pathogenic mutations in NSCLC patients (N = 72). PATHOGENIC MUTATION TOTAL (%) ISOLATED (%) WITH CO-MUTATIONS (%) EGFR 28 (38.9) 18 (25) 12 (16.7)* TP53 13 (18.5) 4 (5.6) 9 (12.5) ROS 1 7 (9.7) 4 (5.6) 3 (4.2) KRAS 6(8.3) 6 (8.3) - PIK3CA 6 (8.3) - 6 (8.3) ALK 4 (5.6) 1 (1.4) 3 (4.2) ERBB2** 3 (4.2) - 3 (4.2) OTHERS: (NRAS,MET,RET,BRAF) - - - PDL1 > 1% 21(29.2) NA NA *2 (25%) had triple mutations; **Escape mutations.