Phase II study of amrubicin plus erlotinib in previously treated, advanced non-small cell lung cancer with wild-type EGFR (TORG1320).

Abstract

e20677 Background: Amrubicin (AMR) is a totally synthetic 9-aminoanthracycline and clinically active against non-small cell lung cancer (NSCLC). We found that the combination of AMR and erlotinib (ERL) had significant synergistic effect on NSCLC cell line with wild-type EGFR in vitro. We conducted a phase I study of AMR and ERL combination therapy in previously treated patients with advanced NSCLC, and have already reported the safety and the effectiveness. Furthermore we observed a high response rate of 33% in EGFR wild-type NSCLC. Methods: We conducted a multi-center, single-arm phase II trial to evaluate the efficacy of AMR and ERL combination therapy in patients with previously treated, advanced NSCLC, PS 0-1, and aged < 75 years, EGFR wild type. Patients were treated at 3weeks intervals with AMR(35mg/m2, intravenous injection on days 1-3) plus ERL(100mg/day, once daily on days 1-21). The primary endpoint is progression free survival (PFS). Secondary endpoints are response rate (RR), disease control rate (DCR), time to treatment failure (TTF), overall survival (OS), and toxicity. The concentration of trough ERL was measured after first cycle of treatment as additional investigation. Results: From June 2013 to July 2016, 25 patients were enrolled in this trial. The PFS according to the central test was 3.6 months (95%CI 2.1 - 5.1). The RR and the DCR were 24.0% and 64.0%, respectively. We observed grade 3 or 4 hematological toxicities such as leukopenia (68%), neutropenia (72%), anemia (8%) and febrile neutropenia (12%). The grade 3 or 4 non-hematological toxicities were anorexia (12%), oral mucositis (12%) and rash (8%). We had no treatment related death in this study. Conclusions: The PFS of AMR and ERL combination therapy in this study was superior to that of AMR monotherapy in historical setting. This combination therapy might be an option for previously treated NSCLC patients without a driver oncogene mutation. Clinical trial information: UMIN 000010582. Clinical trial information: UMIN 000010582.