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ASCO 2019 Annual Meeting

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 (UroToday.com) 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.

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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).

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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

References:
  1. von der Maase H, Sengelov L, Roberts JT, Ricci S, Dogliotti L, Oliver T, Moore MJ, Zimmermann A, Arning M. Long-term survival results of a randomized trial comparing gemcitabine plus cisplatin, with methotrexate, vinblastine, doxorubicin, plus cisplatin in patients with bladder cancer. Journal of clinical oncology. 2005 Jul 20;23(21):4602-8.
  2. Grivas PD, Daignault S, Tagawa ST, Nanus DM, Stadler WM, Dreicer R, Kohli M, Petrylak DP, Vaughn DJ, Bylow KA, Wong SG. Double‐blind, randomized, phase 2 trial of maintenance sunitinib versus placebo after response to chemotherapy in patients with advanced urothelial carcinoma. Cancer. 2014 Mar 1;120(5):692-701.
  3. Powles T, Huddart RA, Elliott T, Sarker SJ, Ackerman C, Jones R, Hussain S, Crabb S, Jagdev S, Chester J, Hilman S. Phase III, double-blind, randomized trial that compared maintenance lapatinib versus placebo after first-line chemotherapy in patients with human epidermal growth factor receptor 1/2-positive metastatic bladder cancer. Journal of Clinical Oncology. 2017 Jan 1;35(1):48-55.
  4. García-Donas, J., Font, A., Pérez-Valderrama, B., Virizuela, J.A., Climent, M.Á., Hernando-Polo, S., Arranz, J.Á., del Mar Llorente, M., Lainez, N., Villa-Guzmán, J.C. and Mellado, B., 2017. Maintenance therapy with vinflunine plus best supportive care versus best supportive care alone in patients with advanced urothelial carcinoma with a response after first-line chemotherapy (MAJA; SOGUG 2011/02): a multicentre, randomised, controlled, open-label, phase 2 trial. The Lancet Oncology, 18(5), pp.672-681.