Pembrolizumab is associated with longer overall survival and fewer treatment-related toxicities vs chemotherapy for patients with advanced urothelial carcinoma.
Second-line pembrolizumab is associated with prolonged overall survival (OS) and fewer treatment-related toxicities compared with chemotherapy for patients with platinum treatment–refractory advanced urothelial carcinomas, according to findings from KEYNOTE-045, an international, open-label, phase III clinical study. The findings were published in the New England Journal of Medicine to coincide with the 2017 American Society of Clinical Oncology (ASCO) Genitourinary Cancers Symposium, held February 16–18 in Orlando, Florida (abstract 282).
Pembrolizumab was associated with an approximately 3-month OS advantage over chemotherapy, reported lead study author Joaquim Bellmunt, MD, PhD, of the Dana-Farber Cancer Institute in Boston, and colleagues. The findings are expected to lead to US Food and Drug Administration approval for this indication.
Pembrolizumab is a human monoclonal antibody that highly selectively targets programmed death 1 (PD-1). The research team randomly assigned 542 patients with recurrence or progression after platinum-based chemotherapy to receive either pembrolizumab (200 mg every 3 weeks) or chemotherapy with paclitaxel, docetaxel, or vinflunine.
Median OS was 10.3 months vs 7.4 months for pembrolizumab and chemotherapy, respectively (hazard ratio [HR], 0.73; 95% CI, 0.59–0.91; P = .002).
“The median OS among patients who had a tumor PD-L1 [programmed death ligand 1] combined positive score of 10% or more was 8.0 months (95% CI, 5.0–12.3) in the pembrolizumab group, as compared with 5.2 months (95% CI, 4.0–7.4) in the chemotherapy group (HR, 0.57; 95% CI, 0.37–0.88; P = .005),” the researchers reported.
Objective response rate was significantly higher for patients receiving pembrolizumab compared with chemotherapy (21% vs 11.4%; P = .001), with a median time to response of 2.1 months for both groups, the authors reported.
Pembrolizumab was associated with fewer treatment-related adverse events (60.9%) vs chemotherapy (90.2%). Fifteen percent of patients receiving pembrolizumab experienced grade 3 or higher adverse events, compared with 49.4% in the chemotherapy group.
“The KEYNOTE-045 trial will have a practice-changing effect,” commented Guru Sonpavde, MD, of the University of Alabama at Birmingham Comprehensive Cancer Center, in an accompanying editorial. “The longer survival and lower rates of toxic effects with pembrolizumab than with chemotherapy confer an improved therapeutic index in these generally elderly patients with coexisting conditions. As we celebrate the major advance that is provided by pembrolizumab, it is important to remember that this remains an incremental advance overall, although the responses were remarkably durable. Patients who require salvage therapy remain incurable.”