Phase 2 study of carboplatin, docetaxel, and bevacizumab as frontline treatment for advanced nonsmall-cell lung cancer.

William N William, Merrill S Kies, Frank V Fossella, Diane D Liu, Gregory Gladish, Warner H Tse, J Jack Lee, Waun K Hong, Scott M Lippman, Edward S Kim

Index: Cancer 116(10) , 2401-8, (2010)

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Abstract

Bevacizumab has recently been demonstrated to prolong overall survival when added to carboplatin and paclitaxel for chemotherapy-naïve patients with nonsquamous nonsmall-cell lung cancer (NSCLC). However, the effects of combining bevacizumab with other standard, front-line, platinum-based doublets have not been extensively explored. We designed this single treatment arm, phase 2 trial to determine whether the combination of carboplatin, docetaxel, and bevacizumab is tolerable and prolongs progression-free survival of chemotherapy-naïve patients with advanced, nonsquamous NSCLC.Forty patients were treated with up to 6 cycles of carboplatin (AUC 6), docetaxel (75 mg/m(2)), and bevacizumab (15 mg/kg) on Day 1 every 21 days. Patients with an objective response or stable disease received maintenance bevacizumab (15 mg/kg) every 21 days until disease progression. The primary endpoint was median progression-free survival. Secondary endpoints included safety, response rates, and overall survival.The median number of chemotherapy and maintenance bevacizumab cycles/patient was 6 and 2, respectively. Grades 3-5 adverse events included febrile granulocytopenia (10%), infections (13%), bleeding (13%), thrombotic events (13%), hypertension (5%), bowel perforation (5%), and proteinuria (3%). Median progression-free survival was 7.9 months and median overall survival was 16.5 months. Partial responses were observed in 21 patients (53%), and stable disease >or=6 weeks occurred in another 17 patients (43%), for a disease control rate of 95%.Carboplatin, docetaxel, and bevacizumab were feasible and effective for front-line treatment of advanced, nonsquamous NSCLC. These data provide further evidence that bevacizumab may be used in combination with multiple standard, platinum-based doublets in this setting.(c) 2010 American Cancer Society.