KEYNOTE-564: Adjuvant pembrolizumab ups survival in kidney cancer

Adjuvant treatment with pembrolizumab has significantly improved overall survival (OS) in patients with clear cell renal cell carcinoma (RCC) who are at high risk of recurrence after surgery, according to an updated analysis of the KEYNOTE-564 trial presented at ASCO GU 2024.

After a median follow-up of approximately 57 months, patients who received adjuvant pembrolizumab achieved a significant improvement in OS compared with those treated with placebo (median OS not reached in both groups; hazard ratio [HR], 0.62; p=0.002). This translated to a 38-percent decrease in the risk of death with pembrolizumab. [ASCO GU 2024, abstract LBA359]

At 48 months, the OS rate was higher in the pembrolizumab arm than in the placebo arm (91.2 percent vs 86.0 percent).

In addition, the OS benefit with pembrolizumab was consistent across all subgroups, regardless of the presence or absence of sarcomatoid features, ECOG PS, or PD-L1 expression status (HR, 0.62).

“Between 1973 and the present, 17 randomized control studies with >12,000 enrolled patients investigated adjuvant therapies in RCC, [with] zero survival improvements and zero OS benefit,” said lead author Dr Toni Choueiri from Dana-Faber Cancer Institute and Harvard Medical School in Boston, Massachusetts, US.

“This is the first study to show a statistically significant and clinically meaningful survival improvement with any adjuvant therapy in kidney cancer,” Choueiri highlighted.

This phase III, multicentre, double-blind study involved 994 patients (median age 60 years) with clear cell RCC, with or without sarcomatoid features, and ECOG PS 0/1 who had undergone nephrectomy and/or resection of metastatic lesions at ≤12 weeks prior to randomization. Participants were randomized to receive either intravenous pembrolizumab 200 mg Q3W for ≥17 cycles (n=496) or placebo (n=498) for about a year. At baseline, majority of the patients (94 percent) had M0 stage disease, and >85 percent had M0 intermediate-high risk disease.

In the interim analysis, KEYNOTE-564 study met its primary endpoint, demonstrating a significant improvement in disease-free survival (DFS) with pembrolizumab vs placebo (HR, 0.68). [N Engl J Med 2021;385:683-694]

In the current updated analysis, pembrolizumab consistently provides better DFS than placebo over a median follow-up period of 57.2 months (HR, 0.72).

The safety profile of pembrolizumab also remained consistent with that observed during the primary analysis, and there were no new safety signals identified, said Choueiri.

Currently, pembrolizumab is approved for use as an adjuvant treatment for patients with RCC who are at intermediate-high or high risk of recurrence after nephrectomy, or after nephrectomy and resection of metastatic lesions.

“Through this study, we now understand that pembrolizumab is more than just a measure to delay recurrence in kidney cancer; it is a means to significantly improve OS for patients,” said Choueiri in a press release. “Considering that many patients with clear cell RCC have a high risk of recurrence leading to incurable distant metastases, this finding is practice changing.”

Overall, adjuvant treatment with pembrolizumab significantly prolonged OS and continued to provide DFS benefits in patients with clear cell RCC at an increased risk of recurrence following surgery. “These results further support adjuvant pembrolizumab as a standard of care after surgery in this disease setting,” Choueiri noted.