Pemetrexed and carboplatin plus bevacizumab with maintenance pemetrexed and bevacizumab as first-line therapy for advanced non-squamous non-small cell lung cancer (NSCLC)

8044 Background: Pemetrexed in combination with carboplatin has been shown to have promising activity, particularily in adenocarcinoma and large cell carcinoma, as well as superior toxicity profile in advanced NSCLC. Bevacizumab has been shown to improve survival of patients with advanced NSCLC when combined with other platin doublets. This study of pemetrexed and carboplatin plus bevacizumab with maintenance pemetrexed and bevacizumab was designed to evaluate toxicities and estimate median time to progression of this novel regimen. Methods: Pts must be chemotherapy naive, stage IIIB (effusion) or IV non-squamous NSCLC, PS 0–1, and have no evidence of CNS metastases. Patients receive pemetrexed 500 mg/m2, carboplatin AUC 6, and bevacizumab 15 mg/kg. Treatment is repeated every 21 days for 6 cycles. For patients with SD or PR, pemetrexed 500 mg/m2 and bevacizumab 15 mg/kg are continued every 21 days until disease progression or toxicity. All patients receive folic acid, vitamin B12 and steroid prophylaxis. Results: From 8/05 - 7/07, 51 patients were enrolled: 45% male, median age 63 (range 34–80.5). One patient enrolled and subsequently refused treatment. Median follow up is 9.5 months. Median # of cycles was 6 (range 1 to 32). 30 patients (60%) completed ≥ 6 cycles of therapy, and 7 (14%) have completed ≥ 18 cycles of therapy. Grade 3/4 toxicities included: anemia (6%/0), thrombocytopenia (0/6%), leucopenia (4%/0); non-hematologic toxicities included: proteinuria (2%/0),venous thrombosis (4%/2%), arterial thrombosis (2%/0), fatigue (8%/0), and diverticulitis (6%/2%). There were no > grade 3 hemorrhagic events nor did any patients experience grade 3/4 hypertension. 49 patients were evaluable for response 1 CR and 23 PRs were observed for ORR of 49% (95% CI, 35 to 61%). 31 of 49 patients have experienced progression with a median time to progression of 7.2 months. 25 of 50 patients have died with a median survival of 14.0 months. Conclusions: Treatment with pemetrexed and carboplatin plus bevacizumab with maintenance pemetrexed and bevacizumab in pts with advanced non-squamous NSCLC is feasible with an acceptable toxicity profile. The encouraging activity justifies further development of this regimen. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Lilly Oncology Lilly Oncology Genentech™ BioOncology, Lilly Oncology Genentech™ BioOncology, Lilly Oncology