For this trial, patients with metastatic urothelial carcinoma whose disease had progressed after platinum-based therapy or were cisplatin ineligible received avelumab 10 mg/kg 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. The Kaplan-Meier method was used to estimate DOR, PFS, and OS. As of September 2016, 249 patients had received avelumab and were followed for ≥6 month (median 13.6 months); 43 patients (17.3%) remained on treatment.
Thirteen patients (5.2%) were cisplatin ineligible, including 7 (2.8%) platinum naïve. Confirmed ORR in all patients (n = 249) was 17.3% (95%CI 12.8–22.5; complete response in 4.4%) and the disease control rate was 44.6%. Response was ongoing in 34/43 patients (79.1%), median DOR was 20.1 months (95%CI 9.7–20.1) and the K-M estimate of DOR of 6 months was 92.7% (95%CI 79.1–97.6). In evaluable patients (n = 206), ORR in PD-L1+ and PD-L1– subgroups (≥5% tumor cell cut-off) was 25.6% and 13.7%, respectively. Median PFS was 1.6 months (95%CI 1.4–2.7), median OS was 8.2 months (95%CI 6.3–10.8), and the K-M OS rate at 12 months was 41.9% (95%CI 34.8–48.7). There were 170 of 249 patients (68.3%) who had a treatment-related adverse event of any grade, most commonly infusion related reaction (23.3%) and fatigue (17.3%). Twenty-six patients (10.4%) had a grade ≥3 treatment-related adverse events, most commonly fatigue (1.6%), elevated lipase (1.6%), and pneumonitis (1.2%). Forty-three patients (17.3%) had an immune-related adverse event (grade ≥3 in 3.6%), and 8 pts (3.2%) discontinued avelumab due to a treatment-related adverse events. There was one treatment-related death (pneumonitis).
In summary, in this updated analysis of the JAVELIN study for patients with metastatic urothelial carcinoma, avelumab showed durable clinical activity and had a manageable and tolerable safety profile irrespective of PD-L1 expression. Importantly, a phase III trial of avelumab as maintenance therapy after first-line platinum-based therapy for advanced urothelial carcinoma is ongoing.
Speaker: Andrea B. Apolo, National Cancer Institutde, Bethesda, United States of America
Co-Authors: J. Ellerton (Las Vegas, United States of America) J. R. Infante (Nashville, United States of America) M. Agrawal (Rockville, United States of America) M. S. Gordon (Scottsdale, United States of America) R. Aljumaily (Oklahoma City, United States of America) C. D. Britten (Charleston, United States of America) L. Dirix (Antwerpen, Belgium) K. Lee (Seongnam, Korea, Republic of) M. H. Taylor (Portland, United States of America) P. Schöffski (Leuven, Belgium) D. Wang (Detroit, United States of America) A. Ravaud (Bordeaux Cedex, France) A. Gelb (Billerica, United States of America) J. Xiong (Billerica, United States of America) G. Rosen (Billerica, United States of America) M. R. Patel (Sarasota, United States of America)
Written By: Zachary Klaassen, MD, Urologic Oncology Fellow, University of Toronto, Princess Margaret Cancer Centre, Twitter: @zklaassen_md at the European Society for Medical Oncology Annual Congress - September 8 - 12, 2017 - Madrid, Spain
Heery CR, O’Sullivan-Coyne G, Madan RA, et al. Avelumab for metastatic or locally advanced previously treated solid tumours (JAVELIN Solid Tumor): A phase 1a, multicohort, dose-escalation trial. Lancet Oncol 2017;18(5):587-598.