Adjuvant Pembrolizumab Extends Disease-Free Survival in High-Risk Renal Cell Carcinoma

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Immunotherapy following surgery significantly improved disease-free survival compared to placebo among patients with high-risk clear cell renal cell carcinoma (RCC), according to results from the international phase III KEYNOTE-564 study presented at the 2021 ASCO Annual Meeting by Toni K. Choueiri, MD, and colleagues (Abstract LBA5). The addition of the immune checkpoint inhibitor pembrolizumab as adjuvant therapy led to a 32% reduction in the risk of disease recurrence or death compared with placebo.

Toni K. Choueiri, MD

Toni K. Choueiri, MD

“KEYNOTE-564 is the first phase III study to show an improvement in disease-free survival with adjuvant immunotherapy in patients with high-risk, fully resected clear cell RCC, the most common type of kidney cancer. The improvement in disease-free survival was statistically significant and clinically meaningful. Pembrolizumab may provide a promising treatment for patients for whom there are few therapy options. KEYNOTE-564’s disease-free survival supports pembrolizumab as a potential new standard of care in RCC,” said lead author Dr. Choueiri, of Dana-Farber Cancer Institute.

RCC is common in both men and women, responsible for 175,000 deaths worldwide in 2018. At diagnosis, most patients present with localized disease, but up to 40% will develop metastatic disease after surgery.

Partial nephrectomy to remove the tumor is commonly used to treat RCC. Patients with intermediate- to high-risk advanced RCC are at risk for relapse, and there are no standard treatment options postsurgery to prevent relapse.

“Despite surgery, recurrence is common in clear cell RCC, and should it recur, there are limited curative treatments for patients. Given the success of pembrolizumab in the KEYNOTE-564 trial, this population may soon have a new standard of care,” said ASCO Chief Medical Officer and Executive Vice President Julie R. Gralow, MD, FACP, FASCO, at a premeeting press conference where these findings were presented.

KEYNOTE-564 Details

KEYNOTE-564 enrolled 994 patients with histologically confirmed clear cell RCC at high risk who had undergone partial nephrectomy at least 12 weeks prior to random assignment. Patients had received no prior systemic therapy. They were randomly assigned to receive adjuvant pembrolizumab for up to 17 cycles or placebo.

The primary endpoint was disease-free survival per investigator’s assessment. Overall survival and safety were secondary endpoints.

At a median follow-up of 24 months, the primary endpoint was met. Median disease-free survival was not met in either treatment arm. Pembrolizumab reduced the risk of recurrence or death by 32% compared with placebo, and this difference was statistically significant (P = .0010).

KEYNOTE-564’s disease-free survival supports pembrolizumab as a potential new standard of care in RCC.
— Toni K. Choueiri, MD

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Twelve-month disease-free survival was 85.7% for pembrolizumab vs 76.2% for placebo. At month 24, the difference in disease-free survival remained about 10% higher in the pembrolizumab group.

Survival data are premature, but at month 24, 94.6% of patients in the pembrolizumab group were alive vs 93.5% of the placebo group, representing a 46% reduction for pembrolizumab. There were 18 deaths in the pembrolizumab group vs 33 in the placebo group. Additional follow-up is planned.

“Safety results were in line with expectations, and there were no new safety signals [seen] with pembrolizumab,” Dr. Choueiri said.

All-cause adverse events were reported in 96.3% of the pembrolizumab group vs 91.1% of the placebo group. Grade 3 to 5 adverse events occurred in 32.4% vs 17.7%, respectively; none of these events led to death.

The study authors concluded, “KEYNOTE-564 is the first positive phase III study with a checkpoint inhibitor in adjuvant RCC, and these results support pembrolizumab as a potential new standard of care for patients with RCC in the adjuvant setting.”

Disclosure: For full disclosures of the study authors, visit


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