Phase II study of everolimus-erlotinib in previously treated patients with advanced non-small-cell lung cancer

Based on the results of a multicenter, open-label, phase II study conducted among patients with previously treated, advanced NSCLC, the combination of everolimus 5 mg/day plus erlotinib 150 mg/day does not warrant further investigation in light of increased toxicity and lack of substantial improvement in disease stabilization compared with erlotinib monotherapy.Preclinical data suggest combining a mammalian target of rapamycin inhibitor with erlotinib could provide synergistic antitumor effects in advanced non-small-cell lung cancer (NSCLC). In this multicenter, open-label, phase II study, patients with advanced NSCLC that progressed after one to two previous chemotherapy regimens were randomized 1:1 to erlotinib 150 mg/day +/- everolimus 5 mg/day. Primary end point was the disease control rate (DCR) at 3 months; secondary end points included progression-free survival (PFS) and safety. One hundred thirty-three patients received everolimus-erlotinib (n = 66) or erlotinib alone (n = 67). The DCR at 3 months was 39.4% and 28.4%, respectively. The probability for the difference in disease control at 3 months to be >= 15% was estimated to be 29.8%, which was below the prespecified probability threshold of >= 40%. Median PFS was 2.9 and 2.0 months, respectively. Grade 3/4 adverse events occurred in 72.7% and 32.3% of patients, respectively. Grade 3/4 stomatitis was observed in 31.8% of combination therapy recipients. Everolimus 5 mg/day plus erlotinib 150 mg/day was not considered sufficiently efficacious per the predefined study criteria. The combination does not warrant further investigation based on increased toxicity and the lack of substantial improvement in disease stabilization.