COPENHAGEN, Denmark — Second-line nivolumab monotherapy demonstrated clinically meaningful efficacy in patients with metastatic or surgically unresectable, locally advanced urothelial cancer, according to phase 2 study results presented at the European Society for Medical Oncology Congress.
Nivolumab (Keytruda, Merck) also exhibited a manageable safety profile.
“[These] data [are] being submitted to support registration of nivolumab for patients with metastatic urothelial cancer that has progressed despite platinum-based chemotherapy, an indication for which the U.S. Food and Drug Administration has granted breakthrough therapy designation to nivolumab,” researcher Matthew Galsky, MD, professor of medicine at Mount Sinai School of Medicine, said in a press release. “Immune checkpoint blockade has become the most promising approach for these patients.”
Patients with platinum-resistant, advanced metastatic urothelial carcinoma who undergo chemotherapy typically have poor objective response rates and achieve poor OS.
Results from the phase 1/phase 2 CheckMate 032 showed nivolumab, a humanized IgG4 anti–PD-1 monoclonal antibody, could be a safe and effective option for this patient population.
In the open-label, single-arm, phase 2 CheckMate 275 study, Galsky and colleagues assessed the safety and efficacy of nivolumab in 265 patients with metastatic or surgically unresectable, locally advanced urothelial carcinoma that progressed after platinum-based chemotherapy.
All patients received nivolumab 3 mg/kg via IV every 2 weeks. Treatment continued until disease progression or unacceptable toxicity.
Overall response rate confirmed by blinded independent review served as the primary endpoint.
After median follow-up of 7 months, 24.4% of patients remained on therapy. Researchers reported an objective response rate of 19.6% (95% CI, 15-24.9).
Galsky and colleagues evaluated response data based on tumor programmed death-1 ligand 1 (PD-L1) expression.
They determined patients whose tumors expressed 5% or more PD-L1 (n = 81) were more likely than those whose tumors expressed 5% or less (n = 184) to achieve complete response (4.9% vs. 1.1%), partial response (23.5% vs. 14.7%) and stable disease (28.4% vs. 20.1%).
Patients with higher PD-L1 expression were more likely to achieve confirmed objective response (28.4% vs. 15.8%) and less likely to experience progressive disease (25.9% vs. 45.1%).
In the entire cohort, median duration of response had not been reached, and 76.9% of responses were continuing at the time of analysis.
Median PFS was 2 months (95% CI, 1.87-2.63) and median OS was 8.74 months (95% CI, 6.05-not reached).
Eighteen percent of patients experienced grade 3 or grade 4 treatment-related adverse events and 1% of patients experienced grade 5 events. The most common adverse events were diarrhea and fatigue. – by Mark Leiser
For more information: Galsky MD, et al. LBA31_PR. Presented at: European Society for Medical Oncology Congress; Oct. 7-11, 2016; Copenhagen, Denmark.
Disclosure: Bristol-Myers Squibb provided funding for this study. Galsky reports stock ownership with Dual Therapeutics; consultant roles with Astellas, Genentech, Merck and Novartis; research funding from Bristol-Myers Squibb, Dendreon, Janssen, Novartis and Merck; and intellectual property with Mount Sinai School of Medicine. Please see the abstract for a list of all other researchers’ relevant financial disclosures.