Gefitinib (G) and Pemetrexed (Pem) as a First Line Treatment in Patients with EGFR Mutant Advanced Non-Small Cell Lung Cancer (NSCLC): A Phase II Study

Background G is the key drug for patient (pts) with NSCLC harboring mutations of EGFR as a first line treatment. However, they have disease progression in most cases. PEM and G are reported to have a schedule-depended cytotoxic synergism. Objectives We evaluated the efficacy and safety of G and PEM as a first line chemotherapy in pts with NSCLC harboring mutations of EGFR. Methods Eligibilities were histologically or cytologically proven non-squamous NSCLC with EGFR active mutation, chemotherapy naive, measurable lesion, ECOG PS0-1, adequate organ function, life expectancy longer than 12 weeks and written informed consent. G (250mg/body) was administered on days 2-16 and PEM (500mg/m2) was administered on day 1. This combination was repeated every 3 weeks until progressive disease (PD). Primary endpoint was overall response rate (ORR) and secondary endpoints were toxicities, disease control rate (DCR), progression free survival (PFS), and overall survival (OS). The planed sample size was 26 pts. Results From March 2010 to May 2012, 20 pts were enrolled and eligible: males/females 10/10; median age 66 (range 59-75); PS 0/2 2/18; stage III/IV 1/19; adeno/others 20/0. Nineteen pts were eligible for efficacy and toxicity; a total of 226 cycles (median 12 cycles, range 1-27) was given. Major grade 3/4 toxicities were neutropenia, leucopenia, liver dysfunction and infection, respectively. There was no treatment-related death. ORR was 68.8%, and DCR was 100%. Median PFS is 18.2 months and median OS is not reached. Conclusions This combination showed longer median PFS and acceptable toxicity. Randomized trial of PEM + G compare with G alone is warranted. Disclosure All authors have declared no conflicts of interest.