Erlotinib plus Bevacizumab Is Effective in EGFR-Mutant NSCLC

Targeted inhibition of EGFR with tyrosine kinase inhibitors such as erlotinib extends survival in patients with EGFR-mutant non–small cell lung cancer (NSCLC). However, the long-term efficacy of these inhibitors is diminished by acquisition of resistance, underscoring the need to develop combinatorial therapeutic strategies. Previous studies have suggested that inhibition of VEGF signaling with the monoclonal antibody bevacizumab enhances the efficacy of second-line erlotinib treatment in unselected patients with recurrent NSCLC, prompting Seto and colleagues to investigate this combination as a first-line treatment specifically in patients with EGFR-mutant NSCLC. In an open-label phase II study, 152 patients with advanced EGFR-mutant NSCLC who had not received prior chemotherapy were randomized to receive either erlotinib alone or the combination of erlotinib plus bevacizumab as first-line treatment, and progression-free survival (PFS) was determined as the primary endpoint. Intriguingly, although the median duration of response and the proportion of patients who exhibited an objective response were not significantly different between treatment groups, combined treatment with erlotinib and bevacizumab induced a reduction in tumor size in all patients and significantly prolonged PFS compared with single-agent erlotinib treatment (16.0 months versus 9.7 months). The incidence of serious adverse events was similar among both treatment groups; however, addition of bevacizumab resulted in a somewhat higher incidence of grade 3 or 4 adverse events, including rash, hypertension, proteinuria, and hemorrhagic events. These results support additional clinical studies of this therapeutic regimen to evaluate its effect on overall survival and suggest that the combination of erlotinib plus bevacizumab may be a potential first-line therapeutic strategy in EGFR-mutant NSCLC.

Seto T, Kato T, Nishio M, Goto K, Atagi S, Hosomi Y, et al. Erlotinib alone or with bevacizumab as first-line therapy in patients with advanced non-squamous non-small-cell lung cancer harbouring EGFR mutations (JO25567): an open-label, randomised, multicentre, phase 2 study. Lancet Oncol 2014 Aug 28 [Epub ahead of print].