ASCO GU 2020: Dr. Albiges Recounts Exciting Research in RCC

Laurence Albiges, MD, PhD, ‎medical oncologist and head of the Genitourinary Oncology Unit at Gustave Roussy Institute, in Villejuif, France, recounts exciting research in renal cell carcinoma (RCC) presented at the 2020 Genitourinary (GU) Cancers Symposium.

The 42-month follow-up data from the phase III CheckMate-214 trial were among some of the most important data in RCC that were presented at the 2020 GU Cancers Symposium, according to Albiges. Results showed that the combination of nivolumab (Opdivo) and ipilimumab (Yervoy) showed sustained superior overall response rates, progression-free survival (PFS) and overall survival benefit versus sunitinib (Sutent) in the intention-to-treat (ITT) and intermediate- and poor-risk population of patients with newly diagnosed, advanced RCC. Notably, more patients achieved complete response with the combination, regardless of risk status.

Additionally, the HIF-2α inhibitor MK-6482 showed encouraging data in a phase I/II trial in patients with advanced clear cell RCC (ccRCC). The majority of patients with ccRCC have an alteration in VHL, which leads to HIF-2α activation, making HIF-2α inhibition an attractive strategy. Treatment with the oral agent resulted in an objective response rate (ORR) of 24% in previously treated patients, says Albiges, and responses were seen irrespective of risk status. Moreover, the agent was found to be safe and tolerable, suggesting that it could be an optimal combination partner in VEGF-driven cancers.

Furthermore, the combination of the multikinase inhibitor sitravatinib and nivolumab (Opdivo), which was evaluated in a phase I/II trial in patients with advanced ccRCC following progression on VEGF-targeted therapy, demonstrated the importance of immune checkpoint/VEGF inhibition. The combination led to an ORR of 39% and a median PFS of 10.3 months, which is superior to what has historically been reported with either nivolumab or cabozantinib (Cabometyx) monotherapy.

Data from the phase II NIVES trial provided the first robust prospective data regarding the use of radiation therapy plus immune checkpoint inhibition, says Albiges. In the trial, pretreated patients with metastatic disease who received stereotactic body radiotherapy (SBRT) with nivolumab experienced an overall response rate of 17.4% in the ITT analysis, failing to meet the study’s hypothesized rate of 40%. Although the trial showed the safety and feasibility of such an approach, it failed to show the immunogenic effects of SBRT.

Results from the AcSé trial indicated that immune checkpoint inhibition may not play a large role in the majority of patients with metastatic non-clear cell RCC. The results showed that the best ORR was 10% with nivolumab monotherapy. However, patients with collecting duct carcinoma had a best ORR of 25%, suggesting that histology can provide insight on which patient subsets may derive benefit from single-agent PD-1 inhibition.

Regarding other investigational strategies in non-clear cell RCC, Albiges highlights the combination of durvalumab (Imfinzi) and savolitinib, which is being evaluated in patients with papillary RCC.

Albiges also underscores the biomarker research that was presented by Martin Voss, MD, of Memorial Sloan Kettering Cancer Center, as well as data from the NIVOREN GETUG-AFU 26 trial, which evaluated biomarkers of response to immune checkpoint inhibitors. Several biomarkers are under investigation, and ultimately, they will be integrated to help inform treatment selection, says Albiges.

For further perspective on emerging data in RCC, Albiges recommends following the Uromigos group on Twitter (@Uromigos) whose goal is to provide relevant and timely information to the genitourinary oncology community.