KEYNOTE-052 confirms response with pembrolizumab in patients with advanced urothelial cancer
CHICAGO – Pembrolizumab induced clinically beneficial, lasting responses among patients with advanced urothelial cancer who were not fit for treatment with cisplatin, according to updated safety and efficacy data from the KEYNOTE-052 trial presented at the ASCO Annual Meeting.
“Comorbidities and renal impairment preclude many with advanced urothelial cancer from receiving chemotherapy,” the researchers wrote. “Initial results from the phase 2 KEYNOTE-052 trial suggested that first-line pembrolizumab (Keytruda, Merck) is active and safe in cisplatin-ineligible patients with advanced urothelial carcinoma.”
Peter H. O'Donnell, MD, assistant professor of medicine at the University of Chicago, and colleagues presented updated safety and efficacy data from KEYNOTE-052. Patients with advanced urothelial cancer included in the phase 2 trial were ineligible for treatment with cisplatin (ECOG performance status 2; creatinine clearance, ≥ 30 to < 60 mL/min; grade 2 or higher neuropathy/hearing loss; New York Heart Association Class III heart failure) and had not received systemic chemotherapy for advanced disease.
All patients were treated with 200 mg pembrolizumab IV every three weeks. Imaging was first completed at Week 9; it was then done every 6 weeks for the first year of the trial and every 12 weeks after the first year.
Objective response rate as confirmed by independent review of RECIST 1.1 criteria served as the primary endpoint. Researchers evaluated safety and efficacy in 370 patients who received one or more doses of pembrolizumab. They also analyzed correlations between an 18-gene expression profile and IHC PD-L1 combined positive score with ORR.
At the data cutoff point, ORR was 29% (95% CI, 24-34). Complete responses were observed in 7% (n = 25) patients; 22% (n = 81) had partial responses. Stable disease was achieved as the best response among 69 patients (19%), leading to a clinical benefit ratio of 47%.
The median time to response was 2 months (range, 1-5). At the median follow-up point of 8 months (range, 0.1 to 20) in all patients, median duration of response had not been achieved (range, 1+ to 18+ months), and the majority of response (74%) were ongoing.
Sixty-eight and an additional 239 patients reported experiencing any-grade and grade 3 or higher drug-related adverse event. Immune-mediated adverse events occurred in 76 patients.
“Consistent with PD-1 pathway biology, biomarkers [GEP and CPS] showed the expected trends of positive association with response to pembrolizumab,” the researchers wrote. – by Julia Ernst, MS
O’Donnell PH, et al. Abstract 4502. Presented at: ASCO Annual Meeting; June 2-6, 2017; Chicago.
Disclosures: The researchers report no relevant financial disclosures.