Benefit of Pembrolizumab/Axitinib Combo in Intermediate/Poor-Risk RCC


The KEYNOTE-426 study evaluated pembrolizumab plus axitinib vs sunitinib in patients with metastatic RCC with intermediate/poor risk disease and those with sarcomatoid features.

Pembrolizumab plus axitinib significantly improved overall survival, progression-free survival, and response rate as first-line treatment compared with sunitinib in patients with metastatic renal cell carcinoma (RCC) with intermediate/poor risk disease and those with sarcomatoid features, according to results of the KEYNOTE-426 study (abstract 4500) presented at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago.

KEYNOTE-426 randomly assigned patients to pembrolizumab plus axitinib or sunitinib, and showed significant improvement in overall survival (hazard ratio [HR], 0.53; P < .0001), progression-free survival (HR, 0.69; P = .0001), and overall response rate (59.3% vs 35.7%; P < .0001) compared with sunitinib in the intention-to-treat analysis.

“The clinical benefit in terms of survival, progression-free survival and response rate was observed across key subgroups,” said study presenter Brian I. Rini, MD, of Cleveland Clinic Taussig Cancer Institute. “Pembrolizumab plus axitinib is a new standard of care for first-line treatment of advanced clear-cell renal cell carcinoma with overall survival, progression-free survival, and overall response benefit in all IMDC [International Metastatic RCC Database Consortium) risk categories and substantial activity in participants with sarcomatoid RCC.”

The prespecified analysis of patients with intermediate/poor-risk disease showed that risk for death was reduced by 48% with pembrolizumab plus axitinib compared with sunitinib (HR, 0.52; 95% CI, 0.37–0.74.). The 12-month overall survival rate was 87.3% compared with 71.3%, respectively.

This group also experienced an advantage to treatment with pembrolizumab plus axitinib for progression-free survival (HR, 0.67; 95% CI, 0.53–0.85) and overall response rate (55.8% vs 29.5%). There was an almost 4-month improvement in 12-month progression-free survival for patients assigned pembrolizumab plus axitinib (median 12.6 vs 8.2 months).

An exploratory analysis of patients with sarcomatoid features showed that the risk for death was reduced by 42% with pembrolizumab plus axitinib compared with sunitinib (HR, 0.58; 95% CI, 0.21–1.59). The 12-month overall survival rate was 83.4% with pembrolizumab plus axitinib compared with 79.5% with sunitinib). The median overall survival has not been reached in either arm.

Similar improvements in progression-free survival (HR, 0.54; 95% CI, 0.29–1.00) and overall response rate 58.8% vs 31.5%) were seen with pembrolizumab/axitinib assignment compared with sunitinib.

The abstract discussant, Rana R. McKay, MD, of University of California San Diego, emphasized that the data on sarcomatoid disease are from a post-hoc exploratory analysis without central pathology, but that these data highlight that immunotherapy combination therapies seem to yield a dramatic response in patients with sarcomatoid disease who have historically done poorly with traditional therapies.

“Immunotherapy combinations are now the new standard front-line treatment for all patients with metastatic RCC without contraindication,” McKay said.  

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