Phase II trial of bevacizumab plus pemetrexed and carboplatin in previously untreated advanced nonsquamous non-small cell lung cancer

Abstract

18163 Background: A randomized phase III trial has demonstrated the efficacy and safety of high dose bevacizumab (15 mg/kg) with carboplatin and paclitaxel in previously untreated advanced nonsquamous NSCLC (Sandler et al, NEJM 2006). Pemetrexed has also shown significant activity in advanced NSCLC. Clinical investigation of combination bevacizumab (BEV), pemetrexed (PEM) and carboplatin (CARBO) is therefore of interest in this population. Methods: Phase II, open label study in stage IIIB/IV NSCLC: eligible patients have non- squamous histology and no prior chemotherapy, brain metastasis, gross hemoptysis, tumor proximity to major vessels, uncontrolled hypertension or anticoagulation. All patients receive PEM (500 mg/m2), CARBO (AUC 6) and BEV (15 mg/kg) every 21 days. Patients are pretreated with vitamin B12 1,000 mcg every 9 weeks and folic acid 1 mg daily. Responses are assessed every 2 cycles. Patients with CR, PR or SD receive maximum of 6 cycles followed by BEV (15 mg/kg) maintenance. Our primary objective is to determine time to progression and secondary objectives include response rate, overall survival, and safety of the combination. Results: 14 patients (9 female/ 5 male; median age 62 years; range 34–77; 2 stage IIIB/12 stage IV, all ECOG PS 0 or 1) have been entered. Median number of cycles received is 5.5 (range 2 - 15). 12 patients are evaluable for response. 9 patients continued to have disease control at a median duration of 20.2 weeks (range 5–52) with 6 PRs and 3 SDs (response rate 60%; disease control rate 75%). 5 patients proceeded to BEV maintenance with 2 still ongoing. Overall survival data is immature to date. Toxicity data is available for all patients. Grade 3/4 toxicities have included neutropenia (4), nausea/vomiting (2), BEV related allergic reaction (1) and epistaxis (1). Conclusions: Combination BEV, PEM and CARBO is safe, well tolerated and shows promising activity to date. The regimen is not associated with alopecia, neuropathy or arthralgias/myalgias, and is conveniently administered. Enrollment continues and updated results will be presented. No significant financial relationships to disclose.