A phase II trial of induction of erlotinib followed by cytotoxic chemotherapy for EGFR mutation-positive non-squamous non-small cell lung cancer patients.

BACKGROUND: No consensus has been reached regarding the treatment order and timing of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) and cytotoxic chemotherapy administration for EGFR mutation-positive non-small cell lung cancer (NSCLC) patients. METHODS: In this phase II trial, chemotherapy-naïve patients harboring activating EGFR mutations with stage IIIB/IV or post-surgical recurrent non-squamous NSCLC were enrolled. Patients were treated with erlotinib induction at 150 mg/day for 3 months. This was followed by cytotoxic chemotherapy with platinum plus pemetrexed, with or without bevacizumab, when the induction erlotinib achieved a CR or PR. The primary end point was the 1-year progression-free survival (PFS) rate, while the secondary end points were the response rate (RR), PFS, safety, and overall survival (OS). RESULTS: Twenty patients were enrolled in this study. The median age was 63 years. Eighteen patients had stage IV disease, and 2 patients had recurrent disease. Eleven patients achieved a PR after induction of erlotinib and 9 out of 11 patients were switched to chemotherapy. The 1-year PFS rate was 45.0% (90% CI 26.8-63.2), the overall RR was 55.0%, and the median PFS was 10.7 months in the intention-to-treat (ITT) population. Grade 3-4 adverse events were reported for 40% of the patients, including patients with leukopenia (10%), neutropenia (20%), and interstitial pneumonitis, bacterial pneumonia, rash, and nausea (all 5%). CONCLUSIONS: The primary end point of this study was not achieved. However, the therapy was well tolerated and may be a treatment option for a future study with patients responsive to short-term erlotinib treatment. CLINICAL TRIALS REGISTRATION NUMBER: UMIN ID: 000013125.