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Randomized Double-Blind Phase II Study of Maintenance Pembrolizumab Versus Placebo After First-Line Chemotherapy in Patients With Metastatic Urothelial Cancer.
- Source :
-
Journal of clinical oncology : official journal of the American Society of Clinical Oncology [J Clin Oncol] 2020 Jun 01; Vol. 38 (16), pp. 1797-1806. Date of Electronic Publication: 2020 Apr 09. - Publication Year :
- 2020
-
Abstract
- Purpose: Platinum-based chemotherapy for first-line treatment of metastatic urothelial cancer is typically administered for a fixed duration followed by observation until progression. "Switch maintenance" therapy with PD-1 blockade at the time of chemotherapy cessation may be attractive for mechanistic and pragmatic reasons.<br />Patients and Methods: Patients with metastatic urothelial cancer achieving at least stable disease on first-line platinum-based chemotherapy were enrolled. Patients were randomly assigned double-blind 1:1 to switch maintenance pembrolizumab 200 mg intravenously once every 3 weeks versus placebo for up to 24 months. Patients with disease progression on placebo could cross over to pembrolizumab. The primary objective was to determine the progression-free survival. Secondary objectives included determining overall survival as well as treatment outcomes according to PD-L1 combined positive score (CPS).<br />Results: Between December 2015 and November 2018, 108 patients were randomly assigned to pembrolizumab (n = 55) or placebo (n = 53). The objective response rate was 23% with pembrolizumab and 10% with placebo. Treatment-emergent grade 3-4 adverse events occurred in 59% receiving pembrolizumab and 38% of patients receiving placebo. Progression-free survival was significantly longer with maintenance pembrolizumab versus placebo (5.4 months [95% CI, 3.1 to 7.3 months] v 3.0 months [95% CI; 2.7 to 5.5 months]; hazard ratio, 0.65; log-rank P = .04; maximum efficiency robust test P = .039). Median overall survival was 22 months (95% CI, 12.9 months to not reached) with pembrolizumab and 18.7 months (95% CI, 11.4 months to not reached) with placebo. There was no significant interaction between PD-L1 CPS ≥ 10 and treatment arm for progression-free survival or overall survival.<br />Conclusion: Switch maintenance pembrolizumab leads to additional objective responses in patients achieving at least stable disease with first-line platinum-based chemotherapy and prolongs progression-free survival in patients with metastatic urothelial cancer.
- Subjects :
- Adult
Aged
Aged, 80 and over
Antibodies, Monoclonal, Humanized adverse effects
Antineoplastic Agents, Immunological adverse effects
Cross-Over Studies
Disease Progression
Double-Blind Method
Female
Humans
Immune Checkpoint Inhibitors adverse effects
Maintenance Chemotherapy
Male
Middle Aged
Neoplasm Metastasis
Progression-Free Survival
Time Factors
United States
Urologic Neoplasms mortality
Urologic Neoplasms pathology
Urothelium pathology
Antibodies, Monoclonal, Humanized administration & dosage
Antineoplastic Agents, Immunological administration & dosage
Immune Checkpoint Inhibitors administration & dosage
Urologic Neoplasms drug therapy
Urothelium drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1527-7755
- Volume :
- 38
- Issue :
- 16
- Database :
- MEDLINE
- Journal :
- Journal of clinical oncology : official journal of the American Society of Clinical Oncology
- Publication Type :
- Academic Journal
- Accession number :
- 32271672
- Full Text :
- https://doi.org/10.1200/JCO.19.03091