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The Exploratory Research of NSCLC with Concomitant EGFR Mutations and ALK Rearrangements


 Background: Epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) rearrangements are two driver alterations and are generally considered mutually exclusive in non-small cell lung cancer (NSCLC). The prevalence of EGFR/ALK co-alterations in patients with NSCLC is low, and the clinicopathological features and optimal targeted therapies of these subtype of patients are still controversial. Methods: We describe three cases of NSCLC harboring EGFR mutation and ALK rearrangement. All of them received more-line therapies and showed the long-term survival benefit from targeted therapies.In addition, we searched PUBMED, EMBASE and MEDLINE up to September, 2020. 91 EGFR/ALK co-altered patients of NSCLC included for analysis in our study. Survival curves were created by Kaplan-Meier method and group comparison analyses of progression free survival (PFS) were using log-rank test. Result: A total of 91 patients were summarized in our study from previous literatures. The patients of NSCLC with coexisting EGFR mutations and ALK rearrangements are more likely to occur in female, non-smoker, Asian origin, adenocarcinoma, and IV stage. The disease control rate (DCR) of tyrosine kinase inhibitors (TKIs) which targeted EGFR and ALK as first-line targeted therapy was 62% and 78%, respectively. The median PFS on first EGFR-TKI and first ALK-TKI therapy were 5.3 months (95% confidence interval [CI] 1.20 – 9.40 months) and 6.0 months (95% CI 0.00 – 14.69 months) in EGFR/ALK co-altered NSCLC patients. Among patients who were treated with EGFR-TKI as first-line targeted therapy, univariant analysis showed that PFS have no significant difference between male and female (p = 0.22), and there is also no difference between Asian and Caucasian (p =0.939). The median PFS between first- and second-line targeted therapies was 7.0 months (95% CI 4.83 -9.17 months) and 2.0 months (95% CI 0.96-3.05 months) (p = 0.075). Survival curves showed the significantly prolonged PFS between patients without and with CNS metastasis (p = 0.036). Conclusion: Both EGFR-TKIs and ALK-TKIs have been proved their effectiveness to EGFR/ALK double-positive NSCLC patients. The curative effect of combination targeted therapies and sequential treatment regimens are still in exploration.