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Shruti Kate,1 Anuradha Chougule,2 Amit Joshi,1 Vanita Noronha,1 Vijay Patil,1 Rohit Dusane,3 Leena Solanki,1 Priyanka Tiwrekar,2 Vaishakhi Trivedi,1 Kumar Prabhash1
1Department of Medical Oncology, Tata Memorial Hospital, Mumbai, Maharashtra, India; 2Department of Molecular Pathology, Tata Memorial Hospital, Mumbai, Maharashtra, India; 3Department of Biostatistics, Clinical Research Secretariat, Tata Memorial Hospital, Mumbai, Maharashtra, India
Context: The importance of unusual EGFR mutations in patients recently diagnosed with advanced non-small cell lung cancer (NSCLC) is poorly understood. We sought to badyze the demographic profile, outcomes and treatment attributes of these patients.
Patients and methods: We retrospectively investigated 5,738 advanced NSCLC patients undergoing EGFR testing in our center from 2013 to 2017 using internal primer probes on a real-time PCR platform. Descriptive data was accumulated from electronic medical records. The survival graph was calculated using the Kaplan – Meier method and compared between groups using the log-rank test.
Results: Of 1,260 patients with the EGFR mutation, 83 (6.58%) had rare, isolated mutations or different combinations. Rare mutations were more common in men, non-smokers and adenocarcinomas. Overall, Exon 18 G719X, Insertion 20, Exon 20 T790M, Exon 20 S768I and Exon 21 (L858R / L861Q) were present in 9.6%, 19.3%, 12%, respectively. 3.6% and 3.6% of patients. The positivity of the double mutation was found in 50.6% of patients. By clbadifying patients according to their susceptibility to the tyrosine kinase inhibitor (TKI), it was found that the majority of patients exhibited a combination of sensitive and insensitive TKI mutations. The median duration of follow-up was 13 months. Five patients were lost to follow-up. Median progression-free survival at first-line treatment was 6.7 months (95% CI 4.8 to 8.5). The median overall survival of patients who received TKI during the course of their disease course was 20.2 months (95% CI: 11.4-28.9). The median overall survival (MOS) of the entire cohort was 15.8 months (95% CI: 10.1-21.5). Among all the rare mutations, patients with a double mutation had better results, with a mOS time of 22.6 months (95% CI: 8.2 to 37.0). P= 0.005). TKI-sensitive / TKI-insensitive double mutations were found to have a higher SG of 28.2 months (95% CI: 15.2-41.2, P= 0.039) relative to TKI insensitive and TKI-insensitive EGFR mutations.
Conclusion: The unusual mutations of EGFR constitute a heterogeneous group. It is therefore imperative to better understand each subgroup in order to define an optimal treatment.
Keywords: rare mutations of EGFR, advanced NSCLC, tyrosine kinase inhibitors, complex EGFR mutations, double mutations of EGFR
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