Illustration of human kidneys in blue, surrounded by red cancer cells to illustrate renal cell carcinoma before treatment with allogeneic CAR T-cell therapy.
Credit: wildpixel/Getty Images

In a clinical trial, researchers at the Dana-Farber Cancer Institute in Boston, MA, have demonstrated that administering the immunotherapy drug pembrolizumab after surgery can significantly improve overall survival rates for patients with a high risk of recurring kidney cancer.

Published in the New England Journal of Medicine, the study’s findings mark an advancement in kidney cancer treatment, challenging five decades of clinical outcomes.

The Phase III randomized, placebo-controlled KEYNOTE-564 study focused on patients with clear-cell renal-cell carcinoma (ccRCC), the most common type of kidney cancer.

The trial enrolled 994 patients across numerous international locations. Participants were randomly assigned to receive either pembrolizumab or a placebo within 12 weeks after undergoing nephrectomy—the surgical removal of the cancerous kidney.

Pembrolizumab, which targets and blocks a specific molecular pathway that cancer cells use to evade the immune system, was administered once every three weeks for approximately a year. This therapy is designed to enhance the body’s immune system, particularly activating T cells to attack tumor cells more effectively.

The study revealed a remarkable 38% reduction in the risk of death for patients treated with pembrolizumab compared to those who received the placebo.

“We can now tell our patients that pembrolizumab after surgery not only delays recurrences but also helps them live longer,” said Toni Choueiri, MD, the study’s lead investigator and director of the Lank Center for Genitourinary Oncology at Dana-Farber.

Historically, patients with ccRCC faced a 30–50% chance of cancer recurrence following surgery, often leading to metastatic disease which is difficult to cure. Since the first randomized controlled trial in 1973, numerous studies have attempted to improve post-surgical outcomes for these patients.

However, until the KEYNOTE-564 study, none had successfully demonstrated a clear survival benefit from adjuvant therapy—treatments given after the primary surgery to enhance its effectiveness.

The results from this latest analysis, based on a median follow-up period of 57.2 months, confirmed the significant role pembrolizumab can play in not only extending the disease-free period but also the overall survival of patients. This benefit was consistent across various patient subgroups, regardless of cancer stage, risk of recurrence, or immunological biomarkers.

Despite the effectiveness of pembrolizumab, approximately 18% of participants discontinued treatment due to side effects. However, the study reported no treatment-related deaths, and it did not observe any clinically meaningful deterioration in the health-related quality of life among patients.

The FDA approved pembrolizumab as an adjuvant treatment for kidney cancer in 2021, based on earlier results from the KEYNOTE-564 study. Following this approval, the focus of ongoing research has shifted toward enhancing this treatment by potentially combining pembrolizumab with other therapeutic agents, such as the HIF-2 inhibitor belzutifan, to further improve patient outcomes.

The investigators believe that this breakthrough offers renewed hope for patients with kidney cancer, establishing a new standard of care in the post-operative treatment landscape and paving the way for more effective and personalized therapeutic strategies.

Also of Interest