Genetic and treatment profiles of patients with concurrent Epidermal Growth Factor Receptor (EGFR) and Anaplastic Lymphoma Kinase (ALK) mutations

Abstract

Background EGFR and ALK alternations often contribute to human malignancies, including lung cancer. EGFR and ALK mutations are usually sensitive to EGFR-tyrosine kinase inhibitors (TKIs) and ALK-TKIs. Although generally mutually exclusive, these mutations do co-exist in rare cases. This study investigated the frequencies, clinical characteristics, therapeutic efficacies, and genetic profiles of lung cancer patients with EGFR and ALK co-mutations. Methods Patients with concurrent EGFR and ALK mutations were included in this study, which analyzed mutation profiles and treatment histories. SPSS20.0 were used for survival analysis. Results Among 271 ALK-positive (ALK-pos) and 2975 EGFR-positive (EGFR-pos) patients in our database, nine (2.6% of ALK-pos and 0.2% of EGFR-pos) patients had concurrent EGFR and ALK mutations (including three exon19 Indel + EML4-ALK, two exon19 Indel + STRN-ALK, two L858R + L1152R, one L858R + EML4-ALK, and one G719C + S768I + STRN-ALK). Eight patients had at least one type of EGFR-TKIs treatment. The median progression free survival (PFS) of these patients on first-generation EGFR-TKIs was 14.5 months (95% CI: 11 - NR). Of these eight patients, one who progressed on Gefitinib and subsequently on Osimertinib had a T790M + C797G. The other seven EGFR-TKIs resistance patients had no known resistance mutations. No patients had ALK mutations before treatment, so ALK mutations may have developed as resistance mechanisms during EGFR-TKIs therapies. EGFR-TKIs-treated patients with EGFR/ALK L1152R mutations generally had a shorter PFS than patients with other mutation combinations. Conclusions ALK and EGFR mutations coincide at a relatively low frequency in lung cancer patients. ALK mutations developed either synchronously or heterochronously with EGFR mutations. Two ALK mutations (L1152R and STRN-ALK) may co-exist with EGFR mutations at a higher frequency than others. Most EGFR/ALK co-alteration patients (other than the EGFR/ALK L1152R type) can benefit from first line EGFR-TKIs.

Role of molecular testing for malignant pleural effusion in targeted therapy for advanced non‐small cell lung cancer

“…[34][35][36] Therefore, we concluded that the incidence of oncogenic driver genes detected in MPE was similar to that in tumor tissues. The EGFR and ALK co-mutation incidence in our study was 3.3% (2/61), which was higher than that in tumor tissue (<1%), 37 possibly because the tumor cells in the MPE may come from all sites of the tumor. In this respect, MPE specimens could overcome the limitation of tumor heterogeneity and, as mentioned above, this may account for the higher incidence of EGFR T790M mutations.…”

Coexistence of anaplastic lymphoma kinase rearrangement in lung adenocarcinoma harbouring epidermal growth factor receptor mutation: A single-center study

“…In addition, Mohapatra et al [ 19 ] pointed out that, owing to economic stress, clinicians in developing countries preferred to choose EGFR-TKIs as the first-line targeted drugs for NSCLC patients with co-mutations of EGFR and ALK genes. Moreover, Yang et al [ 20 ]reports for the first time that EGFR-TKIs-treated patients with EGFR/ALK-L1152R mutations generally had a shorter PFS than patients with other mutation combinations(the mPFS of 4 mo vs 18.2 mo, P < 0.05).…”