A phase II study of bevacizumab and erlotinib as initial treatment for metastatic non-squamous, non-small cell lung cancer with serum proteomic evaluation.

Background: Erlotinib alone or bevacizumab in combination with chemotherapy improve survival in patients with advanced non-small cell lung cancer. The current trial of erlotinib and bevacizumab was designed as an alternative to initial conventional chemotherapy for advanced lung cancer and a platform to explore selection factors.

Methods: Eligibility criteria included stage IIIB/IV or recurrent non-squamous, non-small cell lung cancer (NSNSCLC), no prior chemotherapy for metastatic disease, PS=0-1, and no history of brain metastases for the first 40 patients. An expansion cohort of an additional 10 patients allowed treated brain metastases. Patients received erlotinib 150 mg/day and bevacizumab 15 mg/kg/3 weeks until objective or symptomatic progression. Pretreatment serum was collected for blinded VeriStrat® evaluation.

Results: Fifty patients were accrued. The median age was 65 years, 10 were octogenarians, 37 had PS=1, 25 were female and 12 were never-smokers. Histologies were adenocarcinoma in 26 and unspecified in 24. Partial responses were observed in 12 (24%), stable in 30 (60%) and progressive disease in 8 (16%). The median time on therapy was 15.5 weeks. The median survival was 50.4 weeks with 1 and 2 years survivals of 50% and 21%, respectively. Only 38% of eligible patients received second line therapy, most often due to decline in PS. VeriStrat® analysis was performed in 42 subjects (Good 32, Poor 9, and Indeterminate 1). Significant differences based on VeriStrat® signature were noted in PFS (Good=18.9 weeks, Poor=6.3 weeks, p=0.0035) and overall survival (Good=71.4 weeks, Poor=19.9 weeks, p=0.0015).

Conclusions: Survival in an unselected population of patients with NSNSCLC treated with bevacizumab and erlotinib approximated that expected with conventional chemotherapy. VeriStrat® analyses distinguished patients who were likely or unlikely to benefit from this combination.