A Prospective Phase II Trial of First-Line Osimertinib for Patients With EGFR Mutation-Positive NSCLC and Poor Performance Status (OPEN/TORG2040)

Introduction: Osimertinib is the first-line treatment for patients with NSCLC who have EGFR mutations and favorable performance status (PS). Despite the increasing clinical data on osimertinib, evidence for its use in patients with impaired PS remains limited. Therefore, a multicenter phase II trial (OPEN/TORG2040) was conducted to evaluate the efficacy and safety of first-line osimertinib treatment in patients with EGFR mutation-positive NSCLC and a poor PS. Methods: Patients with previously untreated advanced NSCLC harboring EGFR-sensitizing mutations and PS of 2 to 4 were enrolled. Osimertinib (80 mg once daily) was orally administered to eligible patients. The primary end point was objective response rate. The secondary end points were 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 a PS of 2, six with a PS of 3, and two with a PS of 4) were enrolled. The median age was 75 (range, 41–92) years, 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/QoL 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. Conclusions: This prospective study confirmed the efficacy of first-line osimertinib treatment in patients with EGFR mutation-positive NSCLC and poor PS, highlighting the need for interstitial lung disease risk management. Trial registration number: Japan Registry of Clinical Trials Identifier: jRCTs041200100.