Pemetrexed And Carboplatin Plus Bevacizumab For Advanced Non-Squamous Non-Small Cell Lung Cancer (Nsclc): Preliminary Results

7601 Background: Pemetrexed in combination with carboplatin has been shown to have promising activity and favorable toxicity profile in NSCLC. Bevacizumab has been shown to improve response rates and survival in pts with advanced non-squamous NSCLC when combined with carboplatin and paclitaxel. This study of pemetrexed and carboplatin plus bevacizumab was designed to evaluate the toxicity profile and to estimate the activity of the regimen in this pt population. Methods: Eligibility required that pts were chemotherapy-naive, had stage IIIB (effusion)/IV non-squamous NSCLC, PS 0–1, with no evidence of CNS metastases. Pts received pemetrexed 500 mg/m2 over 10 minutes, carboplatin AUC 6 over 30 minutes, and bevacizumab 15 mg/kg over 30–90 minutes on a 21-day cycle for 6 cycles. Pts with SD or PR received pemetrexed 500 mg/m2 and bevacizumab 15 mg/kg every 21 days until disease progression or toxicity. All pts received folic acid, vitamin B12 and steroid prophylaxis. Results: From 8/05 to 9/06, 39 pts (of planned 50) were enrolled: 20 M/19 F; median age 64 (range 41 - 80). One pt enrolled and subsequently refused treatment. Median number of cycles was 6 (range 1–22), and 25/38 (66%) completed at least 6 cycles of therapy. There was no grade 4 hematological toxicity. Grade 3 hematological toxicities were anemia (5%, N=2) and thrombocytopenia (3%, N=1). The most common grade 3/4 non-hematological toxicities included proteinuria (3%, N=1, gr 3), venous thrombosis (3%, N=1, gr 3), infection (3%, N=1, gr 4), and diverticulitis (11%: 8%, N=3, gr 3/3%, N=1, gr 4). 1 pt with diverticulitis experienced bowel perforation that required surgical intervention. The trial was temporally suspended and the group of pts with diverticulitis was analyzed separately. The only risk factor identified was previous history of diverticulitis. One CR, 20 PRs were observed for an overall response rate of 55% (95%, CI 43–75%). Conclusions: Treatment with pemetrexed and carboplatin plus bevacizumab in pts with advanced non-squamous NSCLC is feasible with an acceptable toxicity profile. The encouraging activity justifies further development of this regimen. However, pts with a prior history of diverticulitis should be excluded until this observation can be investigated further. No significant financial relationships to disclose.