Dr Yekedüz on the Importance of the KEYNOTE-564 Trial in Adjuvant ccRCC

Emre Yekedüz, MD, research fellow, Dana-Farber Cancer Institute, discusses results from a case study on a patient with clear cell renal cell carcinoma (ccRCC), highlighting adjuvant treatment options for this individual.

Yekedüz used social media to poll members of the oncology community about the management of RCC to raise awareness for World Kidney Cancer Day, which took place on June 20, 2024. The poll read: “62-year-old man underwent radical nephrectomy for a 75-mm left renal mass diagnosed as ccRCC with sarcomatoid features. Tumor invaded perirenal sinus fat but did not [extend] beyond Gerota’s fascia, with clear surgical margins. Imaging revealed no distant metastases. What’s [the] next step?”

Some poll responders opted for adjuvant sunitinib (Sutent) as the treatment choice for this patient, Yekedüz begins. This decision was likely influenced by clinical trial data demonstrating that adjuvant sunitinib can improve disease-free survival, according to Yekedüz. However, it is important to note that despite this benefit, sunitinib has not generated an overall survival (OS) advantage in this setting, he explains. Therefore, it’s crucial to consider pembrolizumab (Keytruda) as an adjuvant treatment option for RCC, he notes. The rationale for this consideration stems from the findings of the phase 3 KEYNOTE-564 trial (NCT03142334), which indicate that pembrolizumab should be a key option in the adjuvant setting for this patient population, Yekedüz emphasizes.

The importance of discussing how oncologists approach adjuvant therapy for ccRCC cannot be overstated, he shares. KEYNOTE-564 was a landmark trial, as it was the first to demonstrate an improvement in OS in the adjuvant setting for patients with ccRCC. This breakthrough makes it essential to evaluate patients according to their risk categories—specifically, those with intermediate/high-risk or high-risk disease, Yekedüz emphasizes. For patients falling into these categories, pembrolizumab should be strongly considered as a treatment option in the adjuvant setting, he says.

Understanding risk stratification is also critical, he expands. Patients with T2, T3, or grade 4 disease, or those with sarcomatoid features, can be classified as having intermediate/high-risk disease, and those with T4 and node-positive disease are considered to have high-risk disease. Additionally, in the metastatic setting, if there is no evidence of disease, adjuvant pembrolizumab should still be considered, Yekedüz explains. This approach aims to maximize the potential benefits of adjuvant therapy, thereby improving outcomes for patients with RCC, Yekedüz concludes.