Next-Generation Standard of Care for Renal Cell Carcinoma?
The immunomodulatory effects of vascular endothelial growth factor (VEGF) tyrosine kinase inhibitors in combination with immunotherapy may prove to become the next-generation standard of care for patients with renal cell carcinoma, according to Tian Zhang, MD, of Duke University School of Medicine, in Durham, North Carolina. She explored the benefits of these combination therapies, including high disease control rates and high objective response rates compared with immunotherapy alone, at the 2017 International Kidney Cancer Symposium in Miami.
Several phase IB and II trials have shown that VEGF may augment the benefits of immunotherapy in renal cell carcinoma. Responses from combination therapies such as axitinib/avelumab and lenvatinib/pembrolizumab have resulted in “deep, durable responses” and tumor shrinkage, with recorded disease control rates ranging from 78% to 100%, she stated. Generally, the incidence of grade 3 and 4 toxicities was low with many of these combination regimens, and common side effects included diarrhea, hypertension, and fatigue.
Despite the success of these early clinical trials, unanswered questions remain, Dr. Zhang noted. For instance, she asked, “Will [these early high response rates] translate into higher progression-free and overall survivals?” “What biomarkers will improve outcomes and select patients for VEGF/immunotherapy combinations?” More data are needed to determine the optimal combinations of these and sequencing.