Dr Xu on Ongoing Research Initiatives in ccRCC

Wenxin (Vincent) Xu, MD, physician, Dana-Farber Cancer Institute, assistant professor, medicine, Harvard Medical School, highlights ongoing research in patients with renal cell carcinoma (RCC), spotlighting significant developments and emerging updates in patients with non–clear cell RCC (ccRCC).

Recent developments in RCC offer promising avenues for improved patient outcomes, Xu begins. Ongoing trials are generating anticipation, particularly large triplet therapy trials exploring the addition of a third medication to the lenvatinib (Lenvima) plus pembrolizumab (Keytruda) regimen, he reports. Initial results from the phase 3 CLEAR trial (NCT02811861) have already demonstrated the efficacy of lenvatinib plus pembrolizumab in patients with advanced RCC, and the inclusion of a CTLA-4 inhibitor, such as quavonlimab (MK-1308), or a HIF-2α inhibitor, such as belzutifan (Welireg), could enhance treatment responses, offering significant benefits for patients, Xu says.

Additionally, the ongoing phase 3 PDIGREE trial (NCT03793166) is investigating the early introduction of cabozantinib (Cabometyx) to first-line ipilimumab (Yervoy)/nivolumab (Opdivo) therapy in patients with stable disease or non-progressive disease, he expands. This research addresses an important clinical question and may further optimize treatment strategies, according to Xu. Furthermore, smaller trials exploring novel treatment approaches, such as CAR T-cell therapies, show promise, with some phase 1 trials reporting positive clinical responses, Xu reports.

In the realm of non-ccRCC management, although progress has been made, challenges persist compared with the successes achieved in ccRCC management, Xu elucidates. Ongoing trials continue to shed light on treatment options. Additionally, phase 2 trials have shown activity with lenvatinib plus pembrolizumab and cabozantinib plus nivolumab across various non-ccRCC histologies, he continues.

Moving forward, there is a growing emphasis on developing targeted therapies tailored to the biological characteristics of non-ccRCC subtypes, Xu emphasizes. Although navigating the management of these rare histologies poses challenges, concerted efforts by researchers are underway to identify promising compounds based on patient biology rather than extrapolation from ccRCC data, Xu says. With ongoing research and collaboration, the outlook for advancements in non-ccRCC treatment appears promising, with more breakthroughs expected in the future, he concludes.