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Chicago, IL (UroToday.com) Platinum-based chemotherapy for the first-line treatment of patients with metastatic carcinoma of the urothelium is usually administered for a fixed duration, followed by a observation until recidivism. However, blocking PD-1 by pembrolizumab improves the survival of patients with metastatic urothelial cancer despite platinum-based chemotherapy.
"Substitution" treatment includes primary treatment followed by treatment with another treatment modality. There is a precedent for maintenance treatment of metastatic urothelial cancer through three studies evaluating outcomes of progression-free survival. 
Dr. Matt Galsky and colleagues presented the results of their Phase II trial evaluating the maintenance of pembrolizumab versus placebo after first-line chemotherapy in patients with metastatic urothelial cancer.
HCRN GU14-182 was a pilot study conducted in patients with metastatic carcinoma of the urothelium with at least stable disease after 8 cycles of platinum-based first-line chemotherapy. Patients were randomized 1: 1 to receive 200 mg pembrolizumab intravenously every three weeks versus placebo for up to 24 months; patients on placebo could switch to pembrolizumab. Randomization was stratified by visceral metastasis before chemotherapy (yes versus no) and response to first-line chemotherapy (complete response / partial response to stable disease). The primary objective was to determine progression-free survival (PFS) according to IRRECIST in patients treated with pembrolizumab versus placebo. The complete test scheme is as follows:
Between December 2015 and November 2018, 107 patients were randomized to receive placebo (n = 52) compared to pembrolizumab (n = 55). Initial patient characteristics were well-balanced and included approximately 2/3 of patients with visceral metastases, a median of 6 cycles of first-line chemotherapy, 2/3 of patients achieving a complete or partial response and approximately 2/3 of patients receiving cisplatin. chemotherapy-based. Excluding patients with a complete baseline response, the objective response rate was 12% placebo and 22% pembrolizumab. Grade 3-4 treatment-related adverse events occurred in 48% of placebo-treated patients and 56% of pembrolizumab. After a median follow-up of 14.7 months, 41 patients died and 26/52 patients randomized to receive placebo switched to pembrolizumab. PFS was significantly longer in patients randomized to receive pembrolizumab compared to placebo (HR 0.64, 0.41-0.98). Robustness test at maximum efficiency p = 0.036; log-rank p = 0.038):
The mean progression-free survival time limited to 18 months was 5.6 months with placebo and 8.2 months with pembrolizumab (p = 0.023). 
Considering that smoking can increase the response to immunotherapy, Dr. Galsky's team badessed the smoking status (> 2/3 of all smokers in each arm), but did not appreciate the measurable difference between the groups (never / never smoker) stratified by placebo versus pembrolizumab.
Dr. Galsky concluded his presentation of HCRN GU14-182 with several messages to remember:
- Pembrolizumab maintenance therapy with drug switching significantly delays disease progression in patients with metastatic urothelial carcinoma
- The adverse event profile corresponds to the other treatment parameters.
- It should be noted that SSP and OS in PD-L1 positive patients will be reported in the near future.
- The role of PD-1 blocking related to switch maintenance will be clarified by ongoing Phase III studies
Clinical Trial Information: NCT02500121
Presented by: Matt D. Galsky, Department of Medicine, Mount Sinai School of Medicine Icahn, Tisch Cancer Institute, New York, NY
Coauthors: Sumanta K. Pal, Amir Mortazavi, Matthew I. Milowsky, Saby George, Sumati Gupta, Mark T. Fleming, Long H. Dang, Daniel M. Geynisman, Radhika Walling, Robert S. Alter and Erwin L. Robin. , Wang Jue, Shilpa Gupta, David D. Chism, Joel Picus, George Philips, David I. Quinn, Noah M. Hahn, Menggang Yu; City of Hope National Medical Center, Duarte, California; Arthur G. James Cancer Hospital, Ohio State University Wexner Medical Center, Columbus, OH; University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina; Roswell Park Cancer Institute, Buffalo, NY; Huntsman Cancer Institute – Health Care of the University of Utah, Salt Lake City, Utah; Virginia Oncology Associates, American Oncology Research, Norfolk, VA; Ochsner Medical Center, Baton Rouge, LA; Fox Chase Cancer Center, Philadelphia, PA; Community Cancer Center, Indianapolis, IN; John Theurer Cancer Center at Hackensack University Medical Center, Hackensack, NJ; Community Hospital, Munster, IN; University of Arizona Cancer Center at Dignity Health St. Joseph & Medical Center, Phoenix, AZ; Department of Medicine, Center for Masonic Cancer Control, University of Minnesota, Minneapolis, MN; Vanderbilt University Medical Center, Nashville, TN; Washington University at St. Louis School of Medicine, St. Louis, MO; Georgetown Univ Hosp, Washington, DC; USC Norris Comprehensive Cancer Center, Los Angeles, CA; Faculty of Medicine, Johns Hopkins University, Baltimore, MD; Department of Biostatistics and Medical Informatics of the University of Wisconsin, Madison, WI
Written By: Zachary Klabaden, MD, MSc – Assistant Professor of Urology, Georgia Cancer Center, Augusta University / Medical College of Georgia, @zklabaden_md at the ASCO 2019 Annual Meeting # ASCO19, May 31 at June 4, 2019, Chicago, IL, United States
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