New Molecular Targeted Therapeutic Drugs Clinical Results of Bevacizumab in Non-Small Cell Lung Cancer (NSCLC)

Lung cancer is responsible for one-third of all cancer deaths and accounts for more deaths than breast cancer, prostate cancer and colon cancer combined. Approximately 85% of patients who develop lung cancer will die of the disease. This paper reviews the results of clinical studies in which efficacy of bevacizumab, a humanized anti-VEGF MAb, was investigated in patients with lung cancer. Clinical study of bevacizumab in combination with chemotherapy in lung cancer was done initially in a randomized phase II trial. Ninety-nine NSCLC patients were randomized into three arms: carboplatin/paclitaxel (CP) up to 6 cycles, the same chemotherapy plus bevacizumab of 7.5 mg/kg or 15 mg/kg q3w. Life threatening hemorrhages were observed in the bevacizumab arms with an overall incidence of 9% (6/66) to find following risk factors: baseline hemoptysis and histology. A retrospective analysis excluding case of squamous cell carcinoma showed higher activity when CP was combined with bevacizumab: Of note, treatment arms were not balanced for major prognostic factors in this phase II study and no definitive conclusion regarding the optimal bevacizumab dose can be made. Subsequently, the ECOG-designed E4599, a phase III study, based on the findings of the above trial testing carboplatin/paclitaxel (CP) q3w×6 cycles versus CP + bevacizumab 15 mg/kg q3w×6 cycles followed by bevacizumab15 mg/kg q3w until disease progression. Eight-hundred seventy-eight patients were enrolled (444 in the control and 434 patients in the bevacizumab arm). The second interim analysis was done when 484 deaths had occurred. The baseline factors were well balanced between the two treatment arms. Treatment with bevacizumab increased the overall response from 10.0% to 27.2% (p