Dr Tan on the Efficacy and Safety of IO-IO and IO-TKI Combination Regimens in RCC

“There’s activity [with these IO-TKI regimens] across favorable-, intermediate-, and poor-risk populations but are we helping patients live longer without toxicity and with the durability that we’ve seen from IO-IO treatment with ipilimumab plus nivolumab?”

Alan Tan, MD, genitourinary oncology and melanoma specialist, Vanderbilt-Ingram Cancer Center; associate professor, medicine, Division of Hematology Oncology, Vanderbilt University Medical Center, discusses immuno-oncology (IO)–based combination therapies that are available for the frontline treatment of patients with renal cell carcinoma (RCC).

RCC is a heterogeneous solid tumor that lacks a robust collection of biomarkers to aid in treatment selection, Tan begins. Although the International Metastatic RCC Database Consortium risk criteria provide guidance for prognostic categorization, these criteria are not predictive, he says. Emerging research on angiogenic, RNA, and immune-inflamed signatures may refine RCC therapy selection, particularly for IO-IO or IO-TKI combinations in the frontline setting, he explains.

Currently, 4 IO-based doublet regimens are FDA approved for the first-line treatment of patients with RCC. The IO-IO combination of ipilimumab (Yervoy) plus nivolumab (Opdivo) has the longest follow-up data from its pivotal phase 3 trial, CheckMate-214 (NCT02231749), compared with other approved doublet regimens, according to Tan. Additionally, Tan notes that the efficacy and safety profiles are similar between the 3 available IO-TKI regimens: pembrolizumab (Keytruda) plus axitinib (Inlyta), cabozantinib (Cabometyx) plus nivolumab, and lenvatinib (Lenvima) plus pembrolizumab. Common TKI-related toxicities include hand-foot syndrome, dysphonia, taste changes, and fatigue, he reports. These toxicities often necessitate treatment breaks to manage cumulative effects, he adds.

IO-TKI regimens have generally produced greater progression-free survival and overall survival (OS) benefits compared with IO-IO regimens in RCC, Tan continues. However, it remains unclear whether the IO-TKI regimens extend OS compared with the agents used in the comparator arms of their respective pivotal trials, such as sunitinib (Sutent), which is no longer commonly used in RCC, he says. IO-TKI regimens show efficacy across favorable-, intermediate-, and poor-risk subgroups but oncologists question their ability to deliver durable responses without added toxicity, Tan concludes.