2019 ASCO Annual Meeting!
Session: Genitourinary (Nonprostate) Cancer
Type: Oral Abstract Session
Time: Monday June 3, 8:00 AM to 11:00 AM
Location: Arie Crown Theater
Randomized double-blind phase II study of maintenance pembrolizumab versus placebo after first-line chemotherapy in patients (pts) with metastatic urothelial cancer (mUC): HCRN GU14-182.
Genitourinary (Nonprostate) Cancer
2019 ASCO Annual Meeting
J Clin Oncol 37, 2019 (suppl; abstr 4504)
Author(s): Matt D. Galsky, 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, Erwin L. Robin, Jue Wang, Shilpa Gupta, David D. Chism, Joel Picus, George Philips, David I. Quinn, Noah M. Hahn, Menggang Yu; Department of Medicine, Icahn School of Medicine at Mount Sinai, Tisch Cancer Institute, New York, NY; City of Hope National Medical Center, Duarte, CA; 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, NC; Roswell Park Cancer Institute, Buffalo, NY; Huntsman Cancer Institute-University of Utah Health Care, Salt Lake City, UT; Virginia Oncology Associates, US 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's Hospital and Medical Center, Phoenix, AZ; Department of Medicine, Masonic Cancer Center, University of Minnesota, Minneapolis, MN; Vanderbilt University Medical Center, Nashville, TN; Washington University in St. Louis School of Medicine, St. Louis, MO; Georgetown Univ Hosp, Washington, DC; USC Norris Comprehensive Cancer Center, Los Angeles, CA; Johns Hopkins University School of Medicine, Baltimore, MD; University of Wisconsin Department of Biostatistics and Medical Informatics, Madison, WI
Background: Platinum-based chemotherapy for 1st-line treatment of pts with metastatic urothelial cancer (mUC) is typically administered for a fixed duration followed by observation until recurrence. PD-1 blockade with pembro improves survival of pts with mUC progressing despite platinum-based chemotherapy. We explored the potential benefit of earlier use of PD-1 blockade using a "switch maintenance" approach. Methods: Pts with mUC achieving at least stable disease after up to 8 cycles of 1st-line platinum-based chemotherapy were enrolled. Pts were randomized 1:1 to pembro 200 mg IV q3 weeks versus placebo for up to 24 months; pts progressing on placebo could cross over to pembro. Randomization was stratified based on pre-chemotherapy visceral metastases (Y/N) and response to 1st-line chemotherapy (CR/PR vs. SD). The primary objective was to determine the progression-free survival (PFS) as per irRECIST among pts treated with pembro versus placebo. Results: Between 12/2015 and 11/2018, 107 pts were randomized to placebo (n=52) versus pembro (n=55). The baseline pt characteristics are shown in the Table. Pts randomized to placebo and pembro received a median of 6 and 8 cycles, respectively. Excluding patients with baseline CRs, the objective response rate was 12% (5/42) on placebo and 22% (10/46) on pembro. Grade 3-4 treatment emergent adverse events occurred in 48% of pts on placebo and 56% on pembro. At a median follow-up of 14.7 months, 41 pts have died and 26/52 pts randomized to placebo have crossed over to pembro. PFS was significantly longer in patients randomized to pembro vs. placebo (Maximum Efficiency Robust Test p=0.036; log-rank p = 0.038). The 18-month restricted mean progression-free survival time was 5.6 months with placebo and 8.2 months with pembro (p=0.023). Conclusions: Switch maintenance pembro may “deepen” responses achieved with 1st-line chemotherapy. Switch maintenance pembro prolongs PFS in pts with mUC completing 1st-line platinum-based chemotherapy. Clinical trial information: NCT02500121
|Placebo (N=52)||Pembro (N=55)|
|Age, median (range)||65 (44-87)||68 (41-83)|
|Pre-chemo metastatic disease|
|Visceral metastases||32 (62%)||39 (71%)|
|No visceral metastases||20 (38%)||16 (29%)|
|Median # cycles of 1st line chemo||6||5|
|Response to 1st line chemotherapy|
|CR/PR||36 (69%)||40 (73%)|
|SD||16 (31%)||15 (27%)|
|1st line chemo|
|Carboplatin-based||11 (21%)||16 (29%)|
|Cisplatin-based||41 (79%)||39 (71%)|
1. CALGB 90601 (Alliance): Randomized, double-blind, placebo-controlled phase III trial comparing gemcitabine and cisplatin with bevacizumab or placebo in patients with metastatic urothelial carcinoma.