In this abstract, the authors present updated data from a pooled analysis of patients with mUC from the JAVELIN Solid Tumor trial. The JAVELIN study is a Phase 1, open-label, dose-escalation trial of avelumab [antibody targeting programmed death ligand 1 (anti PD-L1)] in multiple solid tumors. They elaborate on the clinical activity of avelumab in this specific disease state (mUC).
Patients with mUC who had progressed after platinum-based therapy or who were cisplatin ineligible were recruited for the study. Included patients received avelumab 10 mg/kg 1-hour IV every 2 weeks until tumor progression or toxicity. Tumors were assessed every 6 weeks by independent review based RECIST v1.1 criteria. Primary endpoints included objective response rate (ORR). Secondary endpoints included duration of response (DOR), progression-free survival (PFS), overall survival (OS), safety (NCI CTCAE v4.0), and tumor PD-L1 expression.
While still recruiting, as of June 2016, 249 pts had received avelumab for a median of 12 weeks (range 2-92) and were followed up for a minimum of 6 weeks. In this study, the primary tumor site for the mUC was upper tract (renal pelvis/ureter) in 23.3% of patients and lower tract (bladder/urethra) in 76.7%. As indicated in the inclusion criteria, the majority of patients (97.2%) had failed prior platinum therapy, but 2.8% were platinum-ineligible.
In all post-platinum pts (n = 242), median PFS was 6.6 weeks (95% CI 6.1-11.6), median OS was 7.4 months (95% CI 5.7-10.3) and 6-month OS rate was 54.9 (95% CI 47.7-61.7).
In a subset of 161 patients who had prior platinum-based therapy and had a minimum of 6 months follow-up, ORR was 17.4% (95% CI 11.9-24.1; complete response in 6.2%) with a disease control rate of 39.8%. Response was ongoing in 23/28 responders, and the 24-week durable response rate was 92.3% (95% CI 72.6-98.0). 35 patients (21%) had tumor shrinkage ≥ 30%. Responses occurred across PD-L1 expression levels tested. ORR was 25.4% in patients with ≥5% PD-L1 expression, while ORR was 13.2% in patients with < 5% PD-L1 expression.
Treatment-related adverse events (TRAE) of any grade occurred in 166/249 pts (66.7%); but only 21 pts (8.4%) had a grade ≥3 TRAE (fatigue [1.6%] and asthenia [0.8%] in > 1 pt). 34 pts (13.7%) had an immune-related AE (grade ≥3 in 2.4%). There was 1 treatment-related death (pneumonitis).
Though ongoing, these reports support the finding that avelumab is relatively well tolerated and has efficacy consistent with other ICI’s. With an approximate 20% ORR, and durable response in patients who do respond, its outcomes are similar to other ICI’s. While these results are promising, and likely led to its FDA approval, confirmatory studies are needed. Indeed, a phase III study comparing avelumba + best supportive care (BSC) vs. BSC alone is ongoing (JAVELIN Bladder 100, NCT02603432).
Clinical Trial Information
Presented By: Andrea B. Apolo, MD, Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD
Co-Author(s): John Allan Ellerton, Jeffrey R. Infante, Manish Agrawal, Michael S. Gordon, Raid Aljumaily, Carolyn D. Britten, Luc Yves Dirix, Keun-Wook Lee, Matthew H. Taylor, Patrick Schöffski, Ding Wang, Alain Ravaud, Arnold Gelb, Junyuan Xiong, Galit Rosen, Manish R. Patel
Institution(s): Nevada Cancer Research Foundation, Las Vegas, NV; Sarah Cannon Research Institute and Tennessee Oncology, PLLC, Nashville, TN; Associates in Oncology, Rockville, MD; Pinnacle Oncology Hematology, A Division of Arizona Center for Cancer Care, HonorHealth Research Institute Clinical Trials Program at the Virginia G. Piper Cancer Center, Scottsdale, AZ; Oklahoma University Medical Center, Oklahoma City, OK; Medical University of South Carolina, Charleston, SC; Sint-Augustinus Hospital, Antwerpen, Belgium; Seoul National University Bundang Hospital, Seongnam, South Korea; Knight Cancer Institute, Oregon Health & Science University, Portland, OR; University Hospitals Leuven, Leuven Cancer Institute, Leuven, Belgium; Henry Ford Health System, Detroit, MI; Groupe Hospitalier Saint Andre - Hopital Saint Andre, Bordeaux Cedex, France; EMD Serono, Inc., Billerica, MA; Florida Cancer Specialists and Research Institute, Sarasota, FL
Written By: Thenappan Chandrasekar, MD, Clinical Fellow, University of Toronto
at the 2017 ASCO Annual Meeting - June 2 - 6, 2017 - Chicago, Illinois, USA
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