Dana-Farber Cancer InstituteImmunotherapy Post-Surgery Improves Overall Survival For Kidney Cancer

A Breakthrough in Kidney Cancer Treatment: Pembrolizumab Shows Survival Benefit

In a significant advancement for kidney cancer care, the KEYNOTE-564 trial has demonstrated that adjuvant therapy with pembrolizumab, an immunotherapy drug, provides a tangible survival benefit for patients with clear-cell renal-cell carcinoma (ccRCC) at high risk of recurrence post-surgery. This marks the first time in five decades that an adjuvant therapy has shown an overall survival advantage in this patient group, heralding a new standard of care and opening avenues for further therapeutic innovations.

Key Points:

• Pembrolizumab Efficacy: Treatment with pembrolizumab post-surgery led to a significant prolongation of overall survival in patients with high-risk clear-cell renal-cell carcinoma, marking a 38% reduction in the risk of death compared to placebo.
• Historical Context: This is the first adjuvant therapy in fifty years to show an overall survival benefit in kidney cancer patients, overturning decades of clinical trial outcomes that failed to extend life post-surgery.
• Study Design: The KEYNOTE-564 trial, a phase 3, randomized, placebo-controlled study, evaluated pembrolizumab as an adjuvant therapy in 994 patients following nephrectomy, showing significant improvement in both disease-free and overall survival.
• Mechanism of Action: Pembrolizumab targets the PD-1 pathway, a method by which cancer cells evade the immune system, enhancing the body’s ability to fight cancer through T cell activation.
• Patient Eligibility: Participants included those with a clear-cell component of their tumor and at intermediate to high risk of recurrence, including some with resected metastases post-nephrectomy.
• Recurrence Rates: Historically, 30-50% of ccRCC patients experience recurrence after surgery, often leading to metastatic disease, which is challenging to cure.
• Safety Profile: Approximately 18% of participants discontinued pembrolizumab due to side effects, but no treatment-related deaths were reported. The therapy did not significantly impact health-related quality of life negatively.
• Future Research Directions: Following the success of pembrolizumab, research is now focusing on combining it with the HIF-2 inhibitor belzutifan to explore potential enhanced benefits.

“Since 1973, more than 12,000 patients with kidney cancer participated in adjuvant studies versus a control arm and none of the studies showed the experimental arm extends lives until now with the KEYNOTE-564 study. We showed pembrolizumab extends survival. It doesn’t only delay recurrence.”
– Toni Choueiri, MD, Lead Investigator, Director of the Lank Center for Genitourinary Oncology at Dana-Farber

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