Phase II Study of Carboplatin and Pemetrexed Followed by Gefitinib for Patients with Advanced Non-Small Cell Lung Cancer Harboring Sensitive EGFR Mutation

Abstract

Background: To evaluate the efficacy, safety and survival of carboplatin and pemetrexed (Cb/Pem) as induction therapy followed by gefitinib (Gef) maintenance in patients with EGFR-positive advanced non-small cell lung cancer (NSCLC). Methods: Eligible patients received 4 courses of Cb (AUC 6 mg/mL-min) /Pem (500 mg/m2), followed by sequential Gef (250 mg once daily). The primary endpoint was the 2-year survival rate. Secondary endpoints were progression-free survival (PFS), overall survival (OS), tumor responses, and the rate of adverse events. Based on an expected rate of 60% and a threshold rate of 40% at 2 years, 54 cases were required with a < 0.1 and |3 < 0.1. This study was to be effective if 28/54 patients survived for > 2 years. If fewer than 12 of the first 29 patients survived beyond 2 years then the trial was to be stopped. Results: 29 patients were enrolled between June 2010 - January 2015 and we performed an interim analysis The median age was 64 years, 27 patients had stage IV, and 2 patients were postoperative recurrence. There were 6 males and 23 females, performance status was 0 and 1 in 17 and 12 patients, and EGFR gene variations were Ex18, Ex19, and Ex21 in 1, 14, and 14 patients. 1 patient wasn't met starting criteria; therefore, 28 patients were analyzed. The median follow-up time was 30.2 months (range 7-65). 16 patients (57.1%) had partial response for Cb/Pem therapy and all of the patients were switched to Gef. The reasons for switching Gef were completion of Cb/Pem in 21 patients, toxicity in 5 patients, and the doctor's judgment in 2 patients. There were no febrile neutropenia or treatment-related deaths. The overall response rate was 85.2%. The 2-year survival rate was 62.9%, PFS was 16.0 months and OS was not met. According to the EGFR gene variants, the PFS was 17.0 and 15.0 months for patients with Ex19 and Ex21. The OS was not met for patients with Ex19 and was 26.0 months for patients with Ex21. Conclusions: Cb and Pem followed by Gef maintenance therapy might be an initial treatment option for advanced EGFR-positive NSCLC patients. This study was decided to stop after the first stage of enrollment because of the slow enrollment and a phase III study had been started.