Clinical phase II trial shows that combining osimertinib and afatinib resistance EGFR recurrent mutation in EGFR-mutant lung cancer

Treatment options for patients with non-small-cell lung cancer (NSCLC) with EGFR mutations are limited due to resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). Osimertinib or afatinib alone, in a preclinical model, created drug-resistant clones with EGFR secondary mutations, but their combination inhibited the emergence of these mutations. In a Phase II trial, we looked into the alternating-dose therapy of osimertinib and afatinib in patients with EGFR-mutant NSCLC. Patients with stage IV NSCLC with an activating EGFR mutation who had never received treatment were included. Every eight weeks, osimertinib (80 mg/day) and afatinib (20 mg/day) were given in alternate cycles. Utilising circulating tumour DNA collected both before and after therapy, genomic analysis was carried out. The median progression-free survival among the 50 enrolled patients was 21.3 months. A total of 70.3% of respondents responded. Overall median survival was not attained. 35 plasma samples were acquired after the development of resistance; 5 of these samples displayed an elevated MET gene copy number and 3 displayed a BRAF mutation. However, no secondary EGFR mutation was found. The effectiveness of our approach was comparable to that of osimertinib alone, as had been observed in untreated advanced NSCLC patients with EGFR mutations in the past. The treatment may stop the emergence of EGFR secondary mutations that lead to medication resistance, despite the small sample size. To determine the importance of this treatment, more research is required.