Combined inhibition of mTOR and EGFR with everolimus (RAD001) and gefitinib in patients with non-small cell lung cancer who have smoked cigarettes: A phase II trial

7575 Background: Most non-small cell lung cancers (NSCLC) are primarily resistant to the EGFR tyrosine kinase inhibitor gefitinib. One strategy to overcome resistance is to block parallel or downstream effectors that maintain tumor growth and proliferation. Preclinical data supports this hypothesis as inhibition of the PIK3CA/Akt/mTOR pathway restores gefitinib sensitivity in resistant cells. In a phase I study, gefitinib (250 mg) and the mTOR inhibitor everolimus (5 mg) were safely administered orally once-a-day (Milton Proc ASCO 2005). This combination induced regressions in patients with NSCLC. To assess the efficacy of this regimen, we designed this phase II trial. Methods: Two cohorts of patients with measurable stage IIIB/IV NSCLC were entered: (1) untreated with chemotherapy and (2) previously treated with cisplatin or carboplatin and docetaxel. A Simon two-stage design proposed to enroll up to 31 patients in each cohort. Response was assessed after 1 month then every 2 months. Pretreatment tumor s...