RESUMEN
The significance of EGFR targeted therapy in the lung adenocarcinoma is paramount. Several controlled clinical trials have reported considerable survival of EGFR mutation positive patients on receiving the EGFR tyrosine kinase inhibitor (TKI). However, the real-world evidence of benefits of EGFR TKI would be further useful to understand how the designated therapeutic regimen benefits the patients. In this study, we report a decade long real-world evidence of EGFR molecular testing in lung cancer at Tata Memorial Hospital (Mumbai, India). Laboratory and hospital records containing basic demographic details, clinical characteristics, treatment regimen, survival outcome were collected retrospectively. Statistical association and survival analysis were performed using the R programming. The cohort includes 9,053 lung cancer patients tested for EGFR mutations during 2011 to 2019. Baseline T790M and compound mutations were the only mutations observed co-occurring while all other EGFR mutations were mutually exclusive. Furthermore, the baseline T790M were also observed to be associated with TTF1 positivity, smoking and local metastasis. Overall survival of the patients harboring co-occurring compound mutations was significantly lesser than the other EGFR positive patients. Overall, our study suggests that EGFR TKI may provide real-world benefit to the lung cancer patients harboring mutually exclusive EGFR mutations. On the other hand, further systematic study is essential to develop better therapeutic regimen for co-occurring baseline EGFR T790M and other compound mutations.
RESUMEN
BACKGROUND: The significance of uncommon EGFR mutations in newly diagnosed advanced non-small-cell lung cancer (NSCLC) patients is incompletely known. We aimed to analyze the demographic profile, outcome, and treatment attributes of these patients. PATIENTS AND METHODS: We retrospectively surveyed 5,738 advanced NSCLC patients who underwent EGFR testing in our center from 2013 to 2017 by in-house primer probes on real time PCR platform. Descriptive data were accumulated from electronic medical records. Survival plot was calculated using Kaplan-Meier method and compared between groups using log-rank test. RESULTS: Out of 1,260 EGFR mutation-positive patients, 83 (6.58%) had uncommon mutations in isolation or in various combinations. Uncommon mutations were more frequent in men, never-smokers, and adenocarcinomas. Overall, exon 18 G719X, exon 20 insertion, exon 20 T790M, exon 20 S768I, and exon 21 (L858R/L861Q) were present in 9.6%, 19.3%, 12%, 3.6%, and 3.6% patients, respectively. Dual mutation positivity was found in 50.6% patients. On classifying patients as per tyrosine kinase inhibitor (TKI) sensitivity, it was found that majority of the patients had a combination TKI sensitive and insensitive mutations. The median duration of follow-up was 13 months. Five patients were lost to follow-up. Median progression-free survival on first line therapy was 6.7 months (95% CI: 4.8-8.5). Median overall survival (OS) of patients who received TKI during the course of their disease was 20.2 months (95% CI: 11.4-28.9). Median overall survival (mOS) of the entire cohort was 15.8 months (95% CI: 10.1-21.5). Among all uncommon mutations, patients with dual mutations did better, with an mOS time of 22.6 months (95% CI: 8.2-37.0, P=0.005). It was observed that TKI sensitive/TKI insensitive dual mutations had a superior OS of 28.2 months (95% CI: 15.2-41.2, P=0.039) as compared to TKI sensitive and TKI insensitive EGFR mutations. CONCLUSION: Uncommon EGFR mutations constitute a heterogeneous group, hence, it is imperative to understand each subgroup more to define optimal treatment.
