Etirinotecan Pegol (NKTR-102) in Third-line Treatment of Patients With Metastatic or Recurrent Non-Small-cell Lung Cancer: Results of a Phase II Study

The present study evaluated etirinotecan pegol for third-line treatment of patients with metastatic non-small-cell lung cancer. Response rate was the primary endpoint; futility would be declared if < 3 responses were seen. Forty patients were enrolled, with two partial responses and prolonged disease stabilization in 18 patients. The study failed to meet its primary endpoint, and further studies are not planned. Background: Third-line treatment options are limited for patients with metastatic non-small-cell lung cancer (NSCLC). Etirinotecan pegol (NKTR-102) is a long-acting topoisomerase-I inhibitor. We conducted a single-arm phase II trial to evaluate its efficacy in third-line treatment. Patients and Methods: Patients aged >= 18 years with histologically proven NSCLC who had received 2 previous systemic therapy regimens, measurable disease, Eastern Cooperative Oncology Group (ECOG) performance status < 1, and adequate end-organ function were eligible. Etirinotecan pegol was administered at a dose of 145 mg/m(2) intravenously once every 3 weeks until progression. The response was assessed every 6 weeks using Response Evaluation Criteria In Solid Tumors, version 1.1. The primary endpoint was the overall objective response rate. The secondary endpoints included progression-free survival (PFS), overall survival (OS) and safety. A Simon 2-stage design was implemented for futility. Results: From January 2013 to January 2015, 40 patients were enrolled. Their median age was 66 years (range, 19-85 years), 45% were female, 30% had an ECOG performance status of 0, 96% were current and former smokers, and 31 had adenocarcinoma. Patients received a median of 3 cycles (range, 2-15) of protocol therapy. The best response was a partial response in 2 patients. The treatment was well tolerated; 3 patients had grade 3 gastrointestinal toxicity attributable to therapy. The median PFS was 2.3 months (95% confidence interval [CI], 1.3-4.4 months), and the median OS was 7.1 months (95% CI 4.2-11.4 months). Conclusions: Etirinotecan pegol was well tolerated and led to 2 partial responses and disease stabilization with this third-line treatment of metastatic NSCLC. However, the study failed to meet its prespecified response rate endpoint. (C) 2017 Elsevier Inc. All rights reserved.