Immunotherapy drug delays recurrence in kidney cancer patients

STATUE: Toni K. Choueiri, MD, Dana-Farber Cancer Institute, led the KEYNOTE-564 clinical trial. Interim results show that adjuvant immunotherapy in renal cancer revealed a 32% reduction in the risk of recurrence or death…. view more

Credit: Dana-Farber Cancer Institute

An immunotherapy drug given after surgery improved disease-free survival rates in kidney cancer patients at high risk of relapse. Interim results from a phase 3 study of adjuvant therapy showed a 32% reduction in the risk of recurrence or death with pembrolizumab compared to placebo. This is the first positive study of immunotherapy in renal cancer patients at high risk of relapse.

BOSTON — Immunotherapy drug treatment after renal cancer surgery extended disease-free survival in patients at high risk of recurrence, according to an interim report of a phase 3 clinical trial of adjuvant immunotherapy in this patient population.

Patients treated with pembrolizumab for nearly a year experienced a longer delay before disease recurrence, compared with those who received a placebo, said Toni K. Choueiri, MD, of the Dana-Farber Cancer Institute, who reported on the KEYNOTE clinical trial. -564 . This translated into a 32 percent decrease in the risk of recurrence or death in the first two years of the trial. Choueiri, the director of the Lank Center for Genitourinary Oncology at Dana-Farber, will present the findings in a plenary presentation to the American Society of Clinical Oncology (ASCO).

“KEYNOTE-564 is the first positive Phase 3 trial of an adjuvant immunotherapy in this setting and represents a potential new standard of care,” said Choueiri, who led the study. The report contained the first pre-specified analysis of the survey data.

Adjuvant treatment is an adjunct therapy given after primary treatment to reduce the risk of the cancer coming back.

Reporting on the results of the KEYNOTE-564 trial to date, Choueiri said the estimated disease-free survival 24 months after surgery was 77.3% with pembrolizumab treatment versus 68.1% with placebo. The study is continuing to see if adjuvant treatment increases overall survival. There have been too few deaths so far to answer the question, but Choueiri said, “the early signs are promising.” The estimated overall survival rate at 24 months was 96.6% with pembrolizumab and 93.5% with placebo.

The KEYNOTE-564 study was designed to evaluate adjuvant immunotherapy following partial or radical nephrectomy (removal of the cancerous kidney) within 12 weeks prior to randomization. The double-blind, phase 3 study, conducted at multiple international sites, included 994 patients who were randomized to pembrolizumab, or placebo, once every three weeks for approximately one year. Pembrolizumab targets a molecular pathway that cancer cells use to evade recognition and destruction by the body’s immune system. By blocking this “checkpoint” pathway, the drug helps free the immune system — primarily with its army of T cells — to fight tumors.

For inclusion in the study, patients were required to have a clear-cell component of their tumor and have a medium to high risk of recurrence. This level of risk was defined as tumor stage 2 with nuclear grade 4 or sarcomatoid differentiation, tumor stage 3 or higher, regional lymph node metastasis or stage M1 (metastases that were surgically removed) with no evidence of disease.

The primary endpoint was disease-free survival, ie time from randomization to first documented recurrence of local or distant renal cell carcinoma or death from any cause. Overall survival, defined as time from randomization to death from any cause, is a secondary endpoint.

Median disease-free survival was not achieved in the pembrolizumab or placebo arms. The estimated percentage of patients who survived at 24 months and did not relapse was 77.3% with pembrolizumab and 68.1% with placebo. The researchers will continue to follow the patients to determine if there is a difference in overall survival between the two arms of the study, which Choueiri said may need additional follow-up.

Most patients in both arms had at least one adverse event and 32.4% of patients in the pembrolizumab arm had a Grade 3-5 adverse reaction versus 17.7% in the placebo arm. No treatment-related deaths were reported with pembrolizumab. The most common adverse events in both groups were fatigue, diarrhea, and itching, and adverse events with the greatest risk difference between the two groups were hypothyroidism, hyperthyroidism, pruritus, and rash. In the AS-treated population, 101 patients (20.7% in the pembrolizumab arm) and 10 patients (2.0% in the placebo arm) discontinued study treatment due to adverse reactions.

In conclusion, the study authors said, “our results support the use of pembrolizumab for patients at medium to high risk of disease recurrence in the adjuvant setting.”

Choueiri said researchers will look for biomarkers to help determine which patients need adjuvant therapy. “There are patients in our study who were most likely cured with surgery alone and did not require adjuvant therapy, and there are patients who received pembrolizumab and yet their disease progressed.”


The research was supported by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.

Pembrolizumab versus placebo as adjuvant therapy after nephrectomy for patients with renal cell carcinoma: Randomized, double-blind, phase 3 KEYNOTE-564 study (abstract LBA5) will be presented virtually at the plenary session on Sunday, June 6, 2021, 1:00 pm – 4:00 pm ET .

For all ASCO-related media inquiries, call or email Victoria Warren, 617-939-5531, Follow the meeting live on Twitter using the hashtag #ASCO21 and follow Dana-Farber on Twitter at @DanaFarberNews.

About Dana-Farber Cancer Institute

Dana-Farber Cancer Institute is one of the world’s leading centers for cancer research and care. Dana-Farber’s mission is to reduce the burden of cancer through scientific research, clinical care, education, community engagement and advocacy. The Institute offers the latest cancer treatments for adults through Dana-Farber/Brigham and Women’s Cancer Center and for children through Dana-Farber/Boston Children’s Cancer and Blood Disorders Center. Dana-Farber is the only hospital in the entire country with a top 6 US News & World Report Best Cancer Hospital in both adult and pediatric care.

As a global leader in oncology, Dana-Farber is committed to a unique and equal balance between cancer research and care, translating the results of discovery into new treatments for patients locally and around the world, with more than 1,100 therapeutic and non-therapeutic clinical taste.

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