Resistance mutations in lung cancer: A perspective from the Mexican population.

Abstract

e20531 Background: Lung cancer (LC) is the leading cause of cancer-related deaths worldwide, with one of the lowest survival rates, representing the 7th cause of cancer deaths in Mexico. Genetic mutations play a crucial role in disease prognosis and targeted treatment options. Key mutations include ALK, EGFR, KRAS, RET, ROS1, and BRAF, which contribute to uncontrolled cell growth. Additionally, resistance co-mutations such as EGFR-SMARCA4, EGFR-STK1, EGFR-KEAP1, PIK3CA, and others, further complicate treatment. Methods: Original, retrospective, and descriptive study approved by the Research and Bioethics Committee: ON24-0024. ≥18-year-old patients with LC diagnosis treated at our University Hospital “Dr. José Eleuterio González” between 2021-2023 who underwent Foundation One CDx testing, were included. Demographic, epidemiologic, histopathologic, genetic, and diagnostic data were obtained from clinical records. Statistical analysis was conducted using IBM SPSS (V26). Fisher's exact test (α = 0.05) was used to evaluate associations between key mutations and clinical characteristics. Primary endpoints: To describe the frequency of relevant genetic mutations associated with LC and resistant co-mutations. There was one missing data that was excluded from the analysis and didn’t have any confounders. Results: A total of 55 patients (28 female, 27 male; mean age 63.69 ± 11.6 years) with LC were evaluated. Histologic subtypes: Adenocarcinoma 47 (83.9%), squamous 7 (12.5%), sarcomatoid 1 (1.7%). A total of 47(83.9%) patients were in Stage IV; 33 (58.9%) without a history of smoking, and 17 (30.3%) with >20 packages/year. The most common comorbidities were hypertension 10 (17.85%), diabetes 17 (30.3%) and COPD 5 (8.9%). Regarding the most frequent mutations in LC: EGFR was present in 26 (46.43%) patients, TP53: 27 (48.21%), KRAS 7 (12.50%), ALK: 7 (12.50%), MET: 6 (10.71%), ROS1: 5 (8.93%), RET: 3 (5.36%), HER2: 3 (5.36%), BRAF: 2 (3.57%), NTRK1: 2 (3.57%). Resistance co-mutations were found in 19 patients (Table1). Statistical analysis demonstrates a significant association between EGFR mutations and smoking (n = 55; p = 0.022), RET mutations and bone (n = 55; p = 0.037) and nodal metastases (n = 55; p = 0.040), NTRK mutations and smoking (n = 55, p = 0.028), and CTNNB1 and CNS metastases. Conclusions: RET mutations in NSCLC have previously been reported in association with brain metastases, unlike our findings, in which they were associated with bone metastases. However, CNS metastases associated with CTNNB1 mutations in our study were similar to those reported in previous literature. Further research and larger studies are needed to characterize this mutational burden and develop treatment approaches. Resistant mutations Frequency EGFR- STK11 1 EGFR- KEAP1 1 EGFR- SMARCA4 1 PIK3CA 4 CTNNB1 3 RBM10 5 RB1 4 TP53 27