CHICAGO — Durvalumab demonstrated an encouraging clinical response and a positive safety profile in patients with locally advanced or metastatic urothelial cancer, according to results presented at the ASCO Annual Meeting.
Tumors with high PD-L1 activity appeared particularly responsive.
“Anti-PD-L1 immunotherapy shows promising clinical activity in urothelial carcinoma,” the researchers wrote. “We report a planned update of the safety and efficacy of durvalumab (Imfinzi, AstraZeneca) in patients with locally advanced or metastatic urothelial carcinoma from a multicenter, phase 1/phase 2, open-label study.”
Noah M. Hahn, MD, associate professor of medicine in the department of oncology and urology at Johns Hopkins University School of Medicine, and colleagues analyzed the safety and efficacy associated with durvalumab in 191 patients. All patients had stage IV disease and almost all patients (99.5%) previously received anticancer treatment; of these, researchers enrolled 95.3% following treatment with platinum chemotherapy.
Participants received durvalumab 10 mg/kg every 2 weeks for up to 12 months or until unacceptable toxicity, progression or initiation of another anticancer agent. The primary endpoints included safety and confirmed objective response rate as determined by blinded, independent central review (RECIST version 1.1 criteria). Key secondary endpoints included duration of response, PFS and OS.
Median follow-up was 5.78 months (range, 0.4-25.9). At data cutoff, patients achieved an ORR of 17.8% (n = 34) — including seven complete responses — regardless of PD-L1 expression. In addition, responses appeared early (median time to response, 1.41 months) and remained durable (median duration of response not reached).
Patients demonstrated a median PFS of 1.5 months (95% CI, 1.4-1.9) and median OS of 18.2 months (95% CI, 8.1-not estimable). OS at one year was 55% (95% CI, 43.9%-64.7%).
PD-L1 expression was high — defined as 25% or more of tumor or immune cells — in 98 patients and low or negative in 79 patients. PD-L1 status could not be confirmed in 14 patients. Confirmed ORR increased in patients with a high PD-L1 status (27.6%; range, 19-37.5) or unknown (21.4%; range, 4.7-50.8).
Grade 3 or grade 4 treatment-related events developed in 6.8% of patients. Grade 3 or grade 4 immune-mediated adverse events occurred in four patients, of whom two discontinued treatment due to acute kidney injury and autoimmune hepatitis (n = 1 each). – by Julia Ernst, MS
Hahn NM, et al. Abstract 4525. Presented at: ASCO Annual Meeting; June 2-6, 2017; Chicago.
Disclosures: Hahn reports that he serves as a consultant or adviser for AstraZeneca/MedImmune, Bristol-Myers Squibb, Genentech/Roche, Health Advances, Inovio Pharmaceuticals, Merck, Oncogenex and Pieris Pharmaceuticals; and receives research funding through his institution from Acerta Pharma, Bristol-Myers Squibb, Genentech/Roche, Heat Biologics, MedImmune/AstraZeneca, Merck, Mirati Therapeutics, Novartis, Oncogenex and Principa Biopharma. Please see the full study for a list of all other researchers’ relevant financial disclosures.