Statistical analysis of a Phase II study of AMG 386 versus AMG 386 combined with anti-VEGF therapy in patients with advanced renal cell carcinoma

The VEGF pathway is associated with angiogenesis and is an important target for molecular therapies for treating Renal Cell Carcinoma. Existing anti-VEGF therapies, including Bevacizumab, Pazopanib, Sorafenib, and Sunitinib, are available to treat this cancer. However, the presence of alternative pathways, such as the angiopoietin-Tie pathway, is hypothesized to lead to anti-VEGF therapy resistance. AMG 386 was developed to treat renal cell carcinoma through the angiopoietin-Tie pathway. In a Phase II randomized clinical trial, the overall response rate of AMG 386 alone and in combination with an anti-VEGF therapy was assessed. We analyzed the data from this trial to evaluate the efficacy of AMG 386. For this Phase II randomized trial, AMG 386 alone and in combination with anti-VEGF therapy were evaluated separately. The primary endpoint was overall response. For this thesis, we compared the two arms, although this was not done for the original trial. ❧ A total of 35 evaluable patients were available in this study, where we evaluated baseline characteristics, toxicity, response, and progression-free survival. Toxicity was summarized by grade and toxicity system; also, using logistic regression, odds ratios were calculated to analyze the association between hematologic and non-hematologic toxicities and baseline explanatory variables. Response was summarized in terms of RECIST Criteria and a waterfall plot. Fisher’s Exact test and Wilcoxon Rank Sum were used to test the difference between baseline explanatory variables in the two treatments. A Kaplan Meier plot and log-rank test were used to analyze progression-free survival. ❧ The primary conclusion is that neither AMG 386 alone or in combination with an anti-VEGF therapy was effective in treating advanced renal cell carcinoma. Only two patients—both in the combination arm—experienced an objective response to treatment, and 37% of the patients in both arms had stable disease as their best response.