A multicenter phase II study of irinotecan (CPT), cisplatin (CIS), and bevacizumab (BEV) in patients with unresectable or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma

4025 Background: BEV is an anti-VEGF-monoclonal antibody that improves survival in colorectal cancer. CPT/CIS is an active combination in the treatment of gastric and GEJ cancers with a median time to tumor progression(TTP) of 4.5 months. We performed this study to evaluate the efficacy and safety of the combination of CPT, CIS, and BEV in the treatment of gastric and GEJ cancers. Methods: Patients with previously untreated metastatic gastric and GEJ adenocarcinomas are eligible. The primary endpoint is to improve median TTP to 7.5 months. Response, survival, and safety are secondary endpoints. Evaluable or measurable disease was required. Patients received BEV 15mg/kg on day 1, CPT 65mg/m2 and CIS 30mg/m2 on days 1 and 8, every 21 days. Response is assessed by RECIST criteria, and CTCv 3.0 was used for toxicity assessment. Results: We have enrolled 24 patients with the following characteristics: median age 55(range 25–67), KPS 80%(70–90%), Male:Female 19:5. We have observed only 3 patients with progression at a median follow up of 3.4 months. The progression free survival at 3 months is 89%(95%CI: 81–100%), and at 6 months, is 76%(52–100%). Median TTP has not been reached. In 16 patients with measurable disease, we have observed 12 confirmed partial responses(75%, 95%CI:47–92%), 3 minor responses(15–29% reduction) and 1 stable disease. The combination therapy has been well tolerated, without an increase in CPT/CIS related toxicity: i.e. grade 3/4 neutropenia, nausea/vomiting, or diarrhea in 8% of patients. However, thromboembolic events were seen in 25% of patients(95%CI:11–45%): 4 patients with asymptomatic pulmonary embolism and 2 patients with deep vein thrombosis. Of 20 patients with their primary tumor in place, 2 patients had a gastric perforation, and another had a near perforation. There was no significant bleeding or toxicity related death. Conclusions: The combination of CPT/CIS/BEV appears active in gastric and GEJ cancers. Though preliminary, the high rates of response and disease control are noteworthy. The combination appears safe, although thromboembolic phenomenon are concerning. Accrual continues. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech