Response to a Combination of Full-Dose Osimertinib and Ceritinib in a Non-Small Cell Lung Cancer Patient with EML4-ALK Rearrangement and Epidermal Growth Factor Receptor Co-Mutation

Abstract

Lung cancer has been the leading cause of cancer-related deaths in both developed and developing countries, with most primary lung cancers being non-small cell lung carcinomas. Treatment for this condition is sometimes individualized. With developments in modern treatment and phase III clinical trial results, epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) and ALK-TKI have proven thier superior effectivity in comparison with the standard platinum-based doublet and are commonly approved as first-line indications in previously untreated advanced non-small cell lung cancer (NSCLC) patients with EGFR or ALK mutations. In the majority of cases, the presence of the ALK rearrangement mutation does not overlap with other mutations in NSCLC. Here, we report a patient with concomitant ALK rearrangement and EGFR mutation treated with a combination of TKIs: osimertinib and ceritinib.

Analysis of Clinical Features and Treatment Strategies in Advanced Lung Adenocarcinoma Patients With Acquired ALK Fusion After Resistance of EGFR-TKIs

“…Due to the pressure of EGFR-TKIs therapy and cloning selection, the subsequent ALK fusion gene mutations then could be detected. In the case of primary double mutation, if one of TKIs is selected for rst treatment, the remaining uninhibited mutant cell lines of ALK or EGFR will continue to grow [11]. But in the case of secondary EGFR-TKIs resistance, the need for combined application of EGFR-TKIs and ALK-TKIs may be related to the phosphorylation level of downstream proteins activated by the signaling pathway [35].…”

“…Previous studies have suggested that EGFR and ALK fusion gene mutations are independent and mutually exclusive molecular events[8] [9] [10]. But with the development and application of Next Generation Sequencing (NGS), the coexistence of EGFR-sensitive mutations and fusion mutations has been gradually con rmed by a number of case reports and clinical studies [11] [12] [13] [14] [15]. Data show that the proportion of primary EGFR mutation and ALK fusion double mutation at initial diagnosis is about 0.3-1.6%[16] [17] [18] [19], while secondary ALK fusion mutation after EGFR-TKIs application is rarely reported.…”