Updated efficacy and safety of avelumab in metastatic urothelial carcinoma (mUC): Pooled analysis from 2 cohorts of the phase 1b Javelin solid tumor study - Abstract
Methods:
Patients with mUC progressed after platinum-based therapy or cisplatin ineligible received avelumab 10 mg/kg 1-hour IV Q2W. Tumors were assessed every 6 weeks by independent review (RECIST v1.1). Endpoints included objective response rate (ORR), duration of response (DOR), progression-free survival (PFS), overall survival (OS), safety (NCI CTCAE v4.0), and tumor PD-L1 expression.
Results:
As of Jun 9, 2016, 249 patients had received avelumab for a median of 12 weeks (range 2-92) and were followed up for a minimum of 6 weeks. Primary tumor site was upper tract (renal pelvis/ureter) in 23.3% and lower tract (bladder/urethra) in 76.7%. 242 patients (97.2%) had progressed on prior platinum therapy and 7 patients (2.8%) were platinum naive. In 161 post-platinum patients with ≥6 months of follow-up, confirmed 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 at data cut (82.1%; median DOR not reached), and the 24-week durable response rate was 92.3% (95% CI 72.6-98.0). Responses occurred across PD-L1 expression levels tested (≥5% and < 5% tumor cell‒staining [25.4% and 13.2%]). 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). Treatment-related adverse events (TRAE) of any grade occurred in 166/249 pts (66.7%); most common (≥10%) were infusion-related reaction (22.9%, all grade ≤2) and fatigue (16.1%). 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).
Conclusions:
Avelumab was well tolerated and showed durable responses in heavily pretreated patients with mUC, irrespective of tumor PD-L1 expression status.
Author(s): Adnrea B. Apolo, 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): Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD; 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
Clinical trial information: NCT01772004
Check out updated research from ASCO 2017