Combined treatment with pembrolizumab and axitinib is superior to sunitinib alone as first-line therapy for locally advanced or metastatic renal cell carcinoma (mRCC), according to research presented at the 2019 Genitourinary Cancers Symposium.
In the phase 3 KEYNOTE-426 trial (ClinicalTrials.gov Identifier: NCT02853331), patients who received the combination treatment had significantly longer overall survival, progression-free survival (PFS), and objective response rate (ORR) compared with those treated with sunitinib, investigator Thomas Powles, MD, PhD, of Barts Health and the Royal Free NHS Trusts, Barts Cancer Institute, and Queen Mary University of London in the United Kingdom, reported. In addition, the combined treatment had a manageable safety profile. Pembrolizumab plus axitinib should be the standard of care for previously untreated locally advanced or metastatic RCC, the authors concluded.
The study included 861 patients who were randomly assigned to receive either pembrolizumab plus axitinib (432 patients) or sunitinib (429 patients). After a median follow-up of 12.8 months, 59% of patients in the combined treatment arm remained on treatment compared with 43.1% of the sunitinib arm. The 12-month survival rate was 89.9% in the pembrolizumab-axitinib arm compared with 78.3% in the sunitinib arm. Median PFS was 15.1 months for patients receiving combination therapy compared with 11.1 months among sunitinib-treated patients. Recipients of pembrolizumab with axitinib had a significant 47% decreased risk of death (hazard ratio [HR], 0.53 [95% CI, 0.38-0.74]; P < .0001) and 31% decreased risk of disease progression (HR, 0.69 [95% CI, 0.57-0.84]; P =.0001) compared with the sunitinib arm. The ORR was significantly higher in the pembrolizumab-axitinib group than the sunitinib group (59.3% vs 35.7%; P <.0001).
All of the subgroups examined, including all International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk and PD-Ll expression subgroups, benefited from the dual regimen, Dr Powles said.
Treatment-related adverse events (AEs) were grade 3 to grade 5 in 62.9% of patients in the pembrolizumab-axitinib group and 58.1% in the sunitinib arm. These events led to discontinuation of treatment with both pembrolizumab and axitinib in the combined treatment group (8.2% of patients), but no patient in the sunitinib arm discontinued treatment due to treatment-related AEs.
Powles T, Rini BI, Plimack ER, et al. Pembrolizumab (pembro) plus axitinib (axi) versus sunitinib as first-line therapy for locally advanced or metastatic renal cell carcinoma (mRCC): phase III KEYNOTE-426 study. Data presented at: 2019 Genitourinary Cancers Symposium; San Francisco, CA; February 14-16. Abstract 543.