Phase II Trial of Bevacizumab plus Pemetrexed and Carboplatin in Previously Untreated Advanced Nonsquamous Non–Small-Cell Lung Cancer

Abstract

<h3>Background</h3> 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 non–small-cell lung cancer (NSCLC; Sandler et al, 2006). Pemetrexed has also shown significant activity in advanced NSCLC. Clinical investigation of bevacizumab/pemetrexed/carboplatin is, therefore, of interest in this population. <h3>Patients and Methods</h3> This is a phase II, open-label study in stage IIIB/IV NSCLC. Eligible patients have nonsquamous histology and no previous chemotherapy, brain metastasis, gross hemoptysis, tumor proximity to major vessels, uncontrolled hypertension, or anticoagulation. All patients receive pemetrexed 500 mg/m², carboplatin (area under the curve of 6), and bevacizumab 15 mg/kg every 21 days. Patients are pretreated with vitamin B₁₂ 1000 μg every 9 weeks and folic acid 1 mg daily. Responses are assessed every 2 cycles. Patients with complete response, partial response, or stable disease receive a maximum of 6 cycles followed by bevacizumab (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. <h3>Results</h3> Twenty-one patients (13 women/8 men; median age, 62 years; range, 36-77 years; 3 stage IIIB; 18 stage IV, all Eastern Cooperative Oncology Group performance status 0/1) have been entered. The median number of cycles received is 6.2 (range, 2-23 cycles). Nineteen patients are evaluable for response. Sixteen patients continued to have disease control at median duration of 20.68 weeks (range, 5-70 weeks; disease control rate, 84.21%) with 6 partial responses (response rate, 32%) and 10 stable diseases. The response rate is comparable with Sandler et al (35%). Eight patients proceeded to bevacizumab maintenance, with 6 still ongoing. Overall survival data are immature to date. Toxicity data are available for all patients. Grade 3/4 toxicities have included neutropenia (n = 7), nausea/vomiting (n = 4), diarrhea (n = 1), hypertension (n = 1), bevacizumab-related allergic reaction (n = 1), and epistaxis (n = 1). There were 5 events of grade 2 proteinuria. <h3>Conclusion</h3> Bevacizumab/pemetrexed/carboplatin 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.