Common and uncommon mutations in NSCLC: Differences in response to treatment with tyrosine kinase inhibitors: A single-center retrospective analysis

Uncommon EGFR mutations are a heterogeneous group, discovered in ∼10% of the population with EGFR-positive non-small cell lung cancer (NSCLC), whose sensitivity to tyrosine-kinase inhibitors is not yet widely demonstrated. We propose to retrospectively analyze how patients with various EGFR mutations respond differently to treatment with tyrosine-kinase inhibitors. 48 patients with EGFR-positive NSCLC were identified and divided into subgroups by mutation. Progression-free survival (PFS), overall survival (OS) and time to treatment failure (TTF) in those who were treated with Afatinib (Giotrif®) were evaluated. Subgroups were compared using the log-rank test and a multivariate analysis was performed. Patients with common mutations, deletion in exon 19 and L85R, had median OS of 31 months (95% CI: 22-51) and 23 months (95% CI: 6-33) and a median PFS of 16 months (95% CI: 9-33) and 10 months (95% CI: 6-22), respectively. OS and PFS, in patients with common mutations, were superior to those with an uncommon mutation with a p value of 0.003 and 0.0001. Patients with mutations in exon 18 and 21 and patients with mutations in exon 20 had the worst outcome with an OS of 6.5 months (95% CI: 4-30) a PFS of 2.5 months (95% CI: 1-4) and an OS of 3 months (95% CI: 2-4) and a PFS of 4.5 (95% CI: 4-5), respectively. Patients with these mutations also had significantly lower TTF. Multivariate analysis confirmed the results: patients with point mutations in exon 19-21 and mutations in exon 20 had the highest risk of death (HR 6.01 CI: 1.02-35.46, p value=0.001 and HR 12.81 CI: 2.46-62.19 p value=0.004).Table: 1000PMutationNo.FrequencyProgression Free Survival (months)Overall survival (months)Del191837.5%15.5 (9-33)31 (22-51)L858R1837.5%10 (6-22)23 (6-33)Complex mutations24.1%8.25 (0.5-16)8.25 (0.5-16)DelIns1948.3%11 (2-30)21.5 (2-43)Exon 18-2148.3%2.5 (1-4)6.5 (4-30)Exon 2024.1%4.5 (4-5)3 (2-4) Open table in a new tab Patients with uncommon mutations respond heterogeneously to tyrosine-kinase inhibitor treatments. Patients with deletion-insertion or complex mutations respond less than patients with common mutations but they are sensitive to treatment, whereas patients with insertion in exon 20 or mutations in exons 18 and 21 respond very poorly.