Discussion
NSCLC, DLTs, diarrhea, toxicity, rash
NSCLC
This is the first prospective phase I study to investigate the effectiveness of afatinib combined with 80 mg osimertinib. The MTD was defined as 30 mg afatinib combined with 80 mg osimertinib. Based on the toxicity profiles found during all study periods, 66.6% of the patients treated with the MTDs of afatinib and osimertinib experienced DLTs or DLT-equivalent toxicity, such as persistent Grade 2 diarrhea lasting 4 days or Grade 3 rash, respectively. Therefore, the RD for further study was defined as 20 mg afatinib combined with 80 mg osimertinib.Data regarding the adequate dose of afatinib for concomitant use with 80 mg osimertinib are limited. One case report suggested that 20 mg afatinib with 80 mg osimertinib was well tolerated and that it reduced the frequency of the G724S clone, as assessed by the plasma cell-free DNA testing [Osimertinib is superior to first-generation EGFR-TKIs used in the first-line treatment of EGFR mutation-positive advanced NSCLC [Secondary EGFR mutations or co-existing uncommon Co-occurring genomic alterations contribute to the heterogeneity of driver-positive NSCLC and Furthermore, RAS-MAPK pathway activations, including We detected an alternative resistant pathway due to gene amplifications, like in A key limitation of this study was the small number of participants. We could not evaluate the efficacy of the combination therapy in patients harboring T790M/