ASCO 2019: Randomized Double-blind Phase II Study of Maintenance Pembrolizumab Versus Placebo After First-line Chemotherapy in Patients with Metastatic Urothelial Cancer: HCRN GU14-182

Chicago, IL ( Although anti-PD-1/L1 checkpoint blockade has made substantial inroads into the treatment landscape of metastatic urothelial cancer, platinum-based chemotherapy constitutes the current standard of care in the first-line setting. Despite initial responses, patients generally develop refractory disease within approximately eight months.1 Previous attempts to establish the efficacy of post-platinum maintenance therapy with oral tyrosine kinase inhibitors2,3 or chemotherapy4 have failed to demonstrate a survival benefit to post-platinum maintenance, though these studies were conducted largely in the pre-immunotherapy era.

Matt D. Galsky, MD, FASCO, presented data from HCRN GU14-182, a Hoosier Cancer Research Network study of post-platinum maintenance immune checkpoint blockade. HCRN GU14-182 was a randomized double-blind phase II study of the PD-1 antibody pembrolizumab versus placebo following first-line platinum-based chemotherapy for metastatic urothelial cancer. Patients with at least stable disease following no more than eight cycles of platinum-based chemotherapy stratified patients by lymph-node only metastases as well as by response to platinum (CR/PR vs SD) and randomized to pembrolizumab (200 mg q3 weeks for up to 24 months) or to placebo. The primary endpoint was progression-free survival by irRECIST.


At baseline, while no statistical differences were noted between study arms, the pembrolizumab arm tended toward older patients (median age 68 vs 65) and a higher prevalence of visceral metastases (71% vs 62%). Most patients achieved a response to platinum (cisplatin in 77% and 65% of the placebo and pembrolizumab arms, respectively), with 69% achieving CR/PR in the placebo arm versus 73% in the pembrolizumab arm.

Investigators utilized a maximum efficiency robust test to examine for differences in progression-free survival between pembrolizumab maintenance and placebo. Accordingly, patients treated with post-platinum pembrolizumab achieved a statistically significant improvement in progression-free survival relative to patients who received post-platinum placebo (P=0.036).


Survival was subsequently stratified by smoking status. While smokers assigned to the placebo arm generally exhibited the worst progression-free survival, no statistically significant differences were observed with respect to smoking status.

Dr. Galsky indicated that while switch-maintenance pembrolizumab significantly improves progression-free survival, overall survival data are not yet matured and will be presented in the future. Data from ongoing phase III trials will further define the role of post-platinum switch-maintenance therapy in metastatic urothelial cancer.

Presented by: Matt D. Galsky, MD, FASCO, Medical Oncologist, Professor of Medicine and of Urology, Tisch Cancer Institute and Icahn School of Medicine at Mount Sinai, New York, NY

Written by: Michael Lattanzi, MD, Internal Medicine Resident, Department of Medicine, NYU School of Medicine, Twitter: @MikeLattanzi at the 2019 ASCO Annual Meeting #ASCO19, May 31- June 4, 2019, Chicago, IL USA

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