Is the Juice Worth the Squeeze? Optimizing Adjuvant Combinations in RCC

The quest to optimize adjuvant therapy for resected renal cell carcinoma (RCC) has led investigators to evaluate intensive combination regimens, but these clinical gains may often come at a cost. Saum Ghodoussipour, MD, dissected the safety and tolerability profile of adding the CTLA-4 inhibitor tremelimumab (Imjudo) to durvalumab (Imfinzi) based on a presentation of the phase 3 RAMPART trial (NCT03288532) at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting. Initially, he explained that dual-agent checkpoint inhibition inherently intensified the immune attack, resulting in a marked escalation of immune-related adverse effects (AEs).

Further critiquing current clinical trial methodologies, he questioned standard quality-of-life metrics, noting that traditional questionnaires are rarely immune directed and often captured after the fact. Looking ahead, Ghodoussipour suggested the field may pivot away from purely immune-based doublets. Instead, the future of personalized RCC care likely relies on combining immunotherapy with targeted agents––such as VEGF inhibitors or belzutifan (Welireg)––to ensure that the therapeutic benefit truly outweighs the toxicity burden.

Ghodoussipour is the director of the Bladder and Urothelial Cancer Program at Rutgers Cancer Institute and an associate professor of Surgery at Rutgers Robert Wood Johnson Medical School.

Transcript:

CancerNetwork®: Were there any unique toxicities with tremelimumab for these patients?

Ghodoussipour: When you add [tremelimumab] to [durvalumab], you’re intensifying the immune attack, so you’re going to get an intensification of immune-related adverse [effects]. They reported on quality of life, and they said it was no different, but we have to look at how we’re assessing quality of life. Not a lot of the quality-of-life questionnaires that exist are immune directed in terms of adverse [effects], and you’re sometimes asking these questions after the fact.

The whole thought that we can maybe do these adjuvant therapies better than single-agent [therapy] is why there is reason and rationale to study combination therapies. [However], if you’re adding immune therapies on top of each other, I think, based on these data, we now see what the effect of that is, and it’s why others are looking at immunotherapy plus targeted agents as well. People have looked at belzutifan, and there are VEGF inhibitors in an ongoing clinical trial at our center right now as well in combination with immunotherapy. It might become a very personalized approach in the future of what you’re adding to a checkpoint inhibitor, and whether [for] the anticipated toxicity: is the juice going to be worth the squeeze?

Reference

Larkin JM, Powles T, Frangou E, et al. Durvalumab monotherapy versus active monitoring for resected primary renal cell carcinoma in RAMPART: an international, phase 3, randomized controlled trial. J Clin Oncol. 2026;44(suppl 17):LBA4511. doi:10.1200/JCO.2026.44.17_suppl.LBA4511