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.

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.

Surgical removal of the tumour 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 tumour cells by blocking a protein (PD-1) on the tumour 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.

In this phase III study, 994 patients were randomised 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 tumour and soft tissue metastases completely resected ≤1 year from nephrectomy.

While early OS results will be presented, patients will be followed for long-term OS data.

“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.

Watch our interview with Dr Choueiri on the study here.

Source: American Society of Clinical Oncology (ASCO)