In the phase 3 KEYNOTE-426 trial, patients with metastatic renal cell carcinoma (mRCC) had significant improvement in overall survival (hazard ratio [HR], 0.53; P<.0001), progression-free survival (HR, 0.69; P=.001), and objective response rate (HR, 59.3% vs 35.7%; P<.0001) and manageable toxicity when treated with pembrolizumab (pembro) plus axitinib (axi) as first-line therapy for mRCC compared with patients treated with sunitinib. The benefit with pembro + axi was seen across all International Metastatic RCC Database Consortium (IMDC) risk groups and regardless of programmed-death-ligand 1 expression. At the 2019 ASCO Annual Meeting, Brian I. Rini, MD, and colleagues presented data for the combined intermediate/poor risk group and for patients with sarcomatoid features.
A total of 861 patients met eligibility criteria, including diagnosed clear cell mRCC, no prior systemic therapy for mRCC, and Karnofsky performance status ≥70. Patients were randomized 1:1 to pembro 200 mg intravenously every 3 weeks for a maximum of 35 cycles plus axi 5 mg orally twice a day (n=432) or sunitinib 50 mg orally once daily (4 weeks on/2 weeks off) (n=429).
The primary end points of interest were overall survival and progression-free survival, validated by blinded, independent central review. A secondary end point was objective response rate. The intermediate/poor risk group was prespecified; the sarcomatoid group was exploratory. Cox proportional hazards model was used to calculate HRs and 95% confidence intervals (CIs). None of the analyses were multiplicity-controlled.
Of all randomized patients, 68.8% (n=592) were IMDC intermediate/poor risk: 294 in the pembro + axi arm and 298 in the sunitinib arm. In patients with intermediate/poor risk, pembro + axi improved overall survival (HR, 0.52; 95% CI, 0.37-0.74; 12-month rate 87.3% vs 71.3%), progression-free survival (HR, 0.67; 95% CI, 0.53-0.85; median 12.6 months vs 8.2 months) and objective response rates (55.8%, 95% CI, 49.4-61.5% vs 29.5%; 95% CI, 24.4-35.1%). Complete response rates were 4.8% (95% CI, 2.6-7.9%) versus 0.7% (95% CI, 0.1-2.4%).
Of the 578 patients with known status, 18.2% (n=105) had sarcomatoid features: 51 in the pembro + axi arm and 54 in the sunitinib arm. In the pembro + axi arm, overall survival was improved compared with the sunitinib arm: HR, 0.58; 95% CI, 0.21-1.59; 12-month rate 83.4% versus 79.5%. Progression-free survival in the pembro + axi arm: HR, 0.54; 95% CI, 0.29-1.00; median not reached versus 8.4 months; overall response rate, 58.8% (95% CI, 44.2-74.4%) versus 31.5% (95% CI, 19.5-45.6%) in patients with sarcomatoid features. Rates of complete response were 11.8% (95% CI, 4.4-23.9%) versus 0% (95% CI, 0.0-6.6%).
“Pembro + axi provides benefit in the combined population of patients with IMDC intermediate or poor risk and in patients whose tumors had sarcomatoid features. The observed benefits were consistent with those seen in the total population,” the researchers said.
Clinical trial information: NCT02853331
Source: Rini BI, Plimack ER, Stus V, et al. Pembrolizumab (pembro) plus axitinib (axi) versus sunitinib as first-line therapy for metastatic renal cell carcinoma (mRCC): Outcomes in the combined IMDC intermediate/poor risk and sarcomatoid subgroups of the phase 3 KEYNOTE-426 study. Abstract of a presentation at the American Society of Clinical Oncology 2019 Annual Meeting, June 3, 2019, Chicago, Illinois.