Dr Braun on the Evolution of Immunotherapy Combinations in RCC

David A. Braun, MD, PhD, assistant professor, medicine (medical oncology), Louis Goodman and Alfred Gilman Yale Scholar, member, Center of Molecular and Cellular Oncology, Yale Cancer Center, discusses considerations with immuno-oncology (IO)/IO regimens vs IO/TKI regimens in patients with renal cell carcinoma (RCC).

Historically, prior to the advent of targeted therapies, cytokine-based immunotherapy was a standard treatment option for patients with kidney cancer, Braun says. However, although some patients responded well to therapies such as high-dose interleukin-2, most needed more effective treatment options, Braun notes. Although the subsequent rise of anti-angiogenic therapies for patients with kidney cancer appeared promising, these agents did not generate durable survival outcomes, instead eliciting responses that, though clinically meaningful, were usually transient, Braun explains.

The emergence of immune checkpoint inhibitors for RCC has redefined the standard of care in the frontline metastatic, adjuvant, and treatment-refractory settings, Braun emphasizes. For most patients with treatment-naive metastatic clear-cell RCC, which comprise approximately 75% of all kidney cancer cases, immunotherapy should be the frontline systemic therapy of choice, according to Braun. Several treatment options exist in this setting, including dual immune checkpoint blockade with nivolumab (Opdivo) plus ipilimumab (Yervoy) and the combination of a PD-1 inhibitor and a TKI, Braun says.

Although he cautions against taking liberties with cross-trial comparisons, since IO/IO regimens have never been compared head-to-head with IO/TKI regimens, he notes that there is likely a role for each of these combinations. For instance, IO/IO regimens elicit particularly durable responses among responders, as seen in trials such as the phase 3 CheckMate 214 trial (NCT02231749), which evaluated nivolumab plus ipilimumab in patients with advanced or metastatic RCC, Braun explains. Additionally, although upfront response rates appear higher with IO/TKI regimens compared with IO/IO regimens, those responses are often transient, Braun adds.

In patients where an upfront response is critical to achieve disease control and tumor shrinkage, Braun tends to favor IO/TKI regimens. However, when long-term responses are a treatment goal, IO/IO regimens may be the optimal choice, Braun concludes.