Outcome of osimertinib-treated patients with epidermal growth factor receptor mutation-positive nonsmall cell lung cancer requiring dose reduction: a secondary analysis of the Reiwa study.

Background: Osimertinib is effective in patients with epidermal growth factor receptor (EGFR) mutation-positive nonsmall cell lung cancer (NSCLC). However, some patients require osimertinib dose reduction because of adverse events. This study assessed the characteristics of osimertinib dose reduction and compared the efficacies of reduced-dose and regular-dose osimertinib.

Methods: This multicenter, prospective, observational study enrolled patients with EGFR mutation-positive NSCLC who started first-line osimertinib treatment between September 2018 and August 2020. We categorized the patients into two groups: those who required dose reduction during osimertinib treatment (reduction group) and those who continued osimertinib treatment at a dose of 80 mg/day without dose reduction (nonreduction group). The primary endpoints were progression-free survival (PFS) and pattern of progression, whereas the secondary endpoints included overall survival (OS) and reasons for osimertinib dose reduction.

Results: Of the included 575 patients, 175 (30.4%) and 400 (69.6%) were classified into the reduction and nonreduction groups, respectively. PFS was significantly better in the reduction group than in the nonreduction group [hazard ratio (HR) = 0.67, 95% confidence interval (CI) = 0.54-0.84; P <0.001]. Meanwhile, the pattern of progression and OS (HR = 0.82, 95% CI = 0.62-1.08; P = 0.15 ) did not differ significantly between the two groups. Osimertinib was reduced due to physician's decision or adverse events and the main reasons were rash and gastrointestinal symptoms such as nausea and diarrhea.

Conclusions: Many patients require osimertinib dose reduction due to adverse events, but this process does not adversely affect the drug efficacy.