A Prospective Phase II Trial of First-line Osimertinib for Patients with EGFR Mutation-positive Non-small Cell Lung Cancer and Poor Performance Status (OPEN/TORG2040).

Introduction: Osimertinib is the first-line treatment for patients with non-small cell lung cancer (NSCLC) who have EGFR mutations and favorable performance status (PS). Despite increasing clinical data on osimertinib, evidence in patients with an impaired PS remains limited. Therefore, a multicenter phase II trial (OPEN/TORG2040) was conducted to evaluate the efficacy and safety of first-line osimertinib for patients with EGFR mutation-positive NSCLC and poor PS.

Methods: Patients with previously untreated, advanced NSCLC harboring EGFR-sensitizing mutations and a PS of 2-4 were enrolled. Osimertinib, 80 mg once daily, was orally administered to eligible patients. The primary endpoint was the objective response rate. The secondary endpoints were the disease control rate, PS improvement rate, patient-reported outcomes, and safety.

Results: Between February 2021 and February 2022, 30 patients with poor PS (22 with PS of 2, 6 with PS of 3, and 2 with PS of 4) were enrolled. The median age was 75 years (range: 41-92), and 18 patients had brain metastases. The objective response rate was 63.3% (90% confidence interval, 46.7-77.9%; one-sided, p = 0.033). Disease control and PS improvement rates were 93.3% and 63.3%, respectively. Global health status/quality of life also improved. Median progression-free and overall survival were 8.0 and 25.4 months, respectively. Eight patients (26.7%) experienced serious adverse events leading to discontinuation, and six (20.0%) experienced interstitial lung disease (ILD).

Conclusions: This prospective study confirmed the efficacy of first-line osimertinib in patients with EGFR mutation-positive NSCLC and poor PS, highlighting the need for ILD risk management.