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

作者：Akerley Wallace^*; Boucher Kenneth; Rich Nathan; Egbert Lyle; Harker Graydon; Bylund Julie; Van Duren Terry; Reddy Chakravarthy

来源：Lung Cancer, 2013, 79(3): 307-311.

DOI：10.1016/j.lungcan.2012.12.005

• Lung cancer
• Serum proteomic evaluation
• Erlotinib
• Bevacizumab
• Chemotherapy
• EGFR mutation

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 (R) 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 (R) analysis was performed in 42 subjects (Good 32, Poor 9, and Indeterminate 1). Significant differences based on VeriStrat (R) 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 (R) analyses distinguished patients who were likely or unlikely to benefit from this combination.

• 出版日期2013-3