Advanced Renal Cell Carcinoma: What is the Role of Adjuvant Therapy?

Contextualizing discussion with clinical trial data and real-world experience, expert hematologist-oncologists consider the role of adjuvant therapy in managing advanced RCC.

Ulka N. Vaishampayan, MBBS:
Do you want to summarize the adjuvant therapy considerations for us, Moshe?

Moshe Ornstein, MD: The adjuvant space has been a challenging space for the last 30 years or so. All the TKI [tyrosine kinase inhibitor] studies were essentially negative except for the S-TRAC study. Taking a step back, many patients are at high risk of relapse, especially patients who have T3a disease and above. The S-TRAC study compares sunitinib vs placebo for a year, and patients had a disease-free survival benefit but no overall survival benefit. The studies are investigating adjuvant immunotherapy for patients with high-risk RCC [renal cell carcinoma] after a nephrectomy. There was a lot of excitement about the KEYNOTE-564 study, in which patients got pembrolizumab vs placebo for a year. That study demonstrated a disease-free survival benefit, both at the first analysis and with an updated analysis. Although we don’t have overall survival data yet, fortunately patients are living longer, so we probably won’t have those data for a while.

There was a lot of excitement—urologists and medical oncologists were excited: “Let’s give pembrolizumab to patients with localized kidney cancer following a nephrectomy.” Then at ESMO [European Society for Medical Oncology Congress] 2022, there were 3 trials: the IMmotion010 trial, which was atezolizumab vs placebo in the adjuvant setting; CheckMate 914, which had the cohort of nivolumab plus ipilimumab vs placebo; and the PROSPER study, which was nivolumab vs observation given in the perioperative setting—before and after. All studies were negative for disease-free survival. There are many reasons, one could speculate, on why that’s the case. But at the end of the day, we’re stuck with 1 positive trial for disease-free survival benefit and 3 negative trials.

When I piece it together, I tell my patients and the urologists that there’s a role for adjuvant immunotherapy. Hopefully, the survival data will pan out. Patient selection is critical. I try to give more adjuvant pembrolizumab to the higher-risk patients and have a more nuanced discussion with the patients who are at lower risk, who hopefully won’t recur. Should they recur, we might have better options for them at that point.

Ulka N. Vaishampayan, MBBS: True.

Moshe Ornstein, MD: What’s it like in your practice?

Ulka N. Vaishampayan, MBBS: You summarized it very well. It’s a treatment dilemma whether to use adjuvant therapy. Going forward, hopefully there will be biomarkers, such as minimal residual disease, that will help us. They’ll get validated enough to help us make those decisions. There’s a huge discussion of the pros and cons and the risk-benefit ratio. For the T4s and lymph node–positive disease, I absolutely offer adjuvant pembrolizumab, especially if it’s an otherwise healthy younger patient, because the risk of relapse is fairly high. In T3 disease, I have mixed feelings. I usually need another high-risk characteristic, such as sarcomatoid rhabdoid features—those tend to be very responsive to immune checkpoint therapy—or another feature that would make me lean toward treating them with adjuvant therapy. The patient response and thought process is very critical in this decision. In adjuvant therapy, in kidney cancer, we’re practicing shared decision-making.

Transcript edited for clarity.

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