ASCO Perspective
“Despite surgery, recurrence is common in clear-cell renal cell carcinoma, and should it recur, there are limited curative treatment options 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.
ALEXANDRIA, Va. — Immunotherapy after surgery significantly improved disease-free survival (DFS) for patients with the most common type of kidney cancer, clear-cell renal carcinoma (RCC). A phase III international study, to be presented at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting, found that pembrolizumab (Keytruda) could offer an effective treatment for patients currently with few other options. KEYNOTE-564 is the first phase III study with a checkpoint inhibitor in the adjuvant setting to improve DFS for patients with high risk fully resected RCC.
Study at a Glance
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Focus |
To determine whether adjuvant immunotherapy with pembrolizumab is effective and safe. |
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Population |
994 patients with histologically confirmed clear-cell renal cell carcinoma (RCC) with:
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Findings |
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Significance |
The findings support adjuvant pembrolizumab as a potential new standard of care to reduce disease recurrence in patients with fully resected intermediate to high-risk clear cell RCC. |
Key Findings
At the study’s first interim analysis with 24 months median follow-up, the risk of disease recurrence or death was reduced by 32% compared with placebo. The 24-month estimated DFS rate was 77.3% with pembrolizumab, compared to 68.1% with placebo. Overall, DFS benefit was consistent across subgroups.
The estimated preliminary OS rate at 24 months was 96.6% with pembrolizumab and 93.5% with placebo.
Grade 3-5 all-cause AEs were more common with pembrolizumab than placebo — 32.4% versus 17.7% with placebo, respectively. No treatment-related deaths occurred in the pembrolizumab arm.
“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 the adjuvant setting to delay disease recurrence for patients with fully resected clear cell RCC,” said lead author Tony Choueiri, MD, who heads the Lank Center for Genitourinary Oncology at the Dana Farber Cancer Institute.
Kidney cancer is common in both men and women. Most patients present with local disease, but up to 40% develop metastatic disease following surgery.1
Surgical removal of the tumor by partial nephrectomy or the entire kidney by radical nephrectomy is commonly used to treat RCC. However, patients with intermediate- to high-risk advanced disease are at risk for relapse. Currently, there are no standard treatment options post-surgery.
Pembrolizumab, an immunotherapy agent that belongs to a class of therapies known as checkpoint inhibitors, improves immune system response to tumor cells by blocking a protein (PD-1) on the tumor cell surface. Because targeting PD-1 has proven to be effective efficacy and safe for the treatment of metastatic RCC, researchers investigated PD-1 as a novel target to prevent disease recurrence following surgery.
About the Study
In this phase III study, 994 pts were randomized 1:1 to receive either pembrolizumab or placebo at least 12 weeks after surgery.
Study primary endpoint was DFS; overall survival (OS) was key secondary endpoint Patients were enrolled if they had histologically confirmed clear-cell RCC with:
Intermediate high risk, high risk, or no evidence of disease after primary tumor and soft tissue metastases completely resected ≤1 year from nephrectomy.
Next Steps
While early OS results will be presented, patients will be followed for long-term OS data.
For your readers:
- Guide to Kidney Cancer
- Understanding Immunotherapy
- Cancer.Net Blog Post (English)
- Cancer.Net Blog Post (Spanish)
View the disclosures for the 2021 Cancer Communications Committee: https://www.asco.org/sites/new-www.asco.org/files/content-files/about-asco/pdf/2021-am-news-planning-team-disclosures.pdf
View the disclosures for Dr. Gralow: https://coi.asco.org/share/CKD-HYVM/Julie%20Gralow
View the disclosures for Dr. Pierce: https://coi.asco.org/share/Z2M-8YDX/Lori
ATTRIBUTION TO THE AMERICAN SOCIETY OF CLINICAL ONCOLOGY ANNUAL MEETING IS REQUESTED IN ALL COVERAGE.
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1. Motzer RJ, Ravaud A, Patard JJ, et al. Adjuvant Sunitinib for High-risk Renal Cell Carcinoma After Nephrectomy: Subgroup Analyses and Updated Overall Survival Results. Eur Urol. 73:62-68, 2018.
About ASCO:
Founded in 1964, the American Society of Clinical Oncology, Inc. (the Society) is committed to the principle that knowledge conquers cancer. Together with the Association for Clinical Oncology, ASCO® represents nearly 45,000 oncology professionals who care for people living with cancer. Through research, education, and promotion of high quality and equitable patient care, ASCO works to conquer cancer and create a world where cancer is prevented or cured, and every survivor is healthy. Conquer Cancer, the ASCO Foundation, supports the Society by funding groundbreaking research and education across cancer’s full continuum. Learn more at www.ASCO.org, explore patient education resources at www.Cancer.Net, and follow us on Facebook, Twitter, LinkedIn, Instagram, and YouTube.