Adjuvant and Neoadjuvant Therapies Under Evaluation for Renal Cell Carcinoma

Expert perspectives on the possible roles of neoadjuvant nivolumab and adjuvant sunitinib for patients with renal cell carcinoma.


Robert J. Motzer, MD:You led the trial at MSKCC [Memorial Sloan Kettering Cancer Center] with neoadjuvant nivolumab in RCC [renal cell carcinoma], which has recently been published, and I know there is a large trial going on, the PROSPER trial. What are your thoughts in terms of the neoadjuvant trial? Is that a part of our standard of care or investigational, or how do you see that?

Maria I. Carlo, MD: It’s definitely investigational. We don’t have compelling evidence to show that this is a better approach. There’s certainly biologic rationale for why a neoadjuvant approach with more tumor in place, immune therapy would have greater efficacy. That’s still at least an RCC theory but has not been proven. We look forward to larger trials. In our experience, in our small, published trial, we used single-agent nivolumab, 4 doses prior to nephrectomy. Although we didn’t see any significant tumor shrinkage, we also didn’t see a high rate of complications, and all patients proceeded to nephrectomy without delay. We look forward to further study of the kidney specimens, tumor infiltration, what’s their rate of recurrence afterward, to see if this approach does lead to better outcomes than an adjuvant approach.

Robert J. Motzer, MD: Sunitinib was also approved in this space, based on the S-TRAC trial. Joe, is there still a role for sunitinib in adjuvant therapy, or has that been outdated now or replaced here?

Chung-Han Lee, MD:S-TRAC was a positive trial that looked at and demonstrated a disease-free survival. However, taken in the context of the other TKI [tyrosine kinase inhibitor] trials in the adjuvant setting that did not necessarily show a benefit from a disease-free survival standpoint, the key difference within the S-TRAC trial was the use of sunitinib at the 50-mg, 4 weeks on, 2 weeks off starting dose. Historically that’s been a challenging regimen for patients, and a lot of the patients did end up seeing a lot more toxicity related to using adjuvant TKIs. Having an adjuvant option that is IO [immunotherapy]-based, in which generally from a quality of life standpoint is much better tolerated, is definitely a benefit for the patients. Certainly in discussion with the patients, their preference often is something like an IO, immunotherapy, despite the fact that it’s switching you from an oral agent to an IV [intravenous] agent, from the overall quality of life standpoint.

Transcript edited for clarity.

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