Avelumab treatment of metastatic urothelial carcinoma (mUC) in the phase 1b JAVELIN solid Tumor study: Updated analysis with ≥6 months of follow-up in all patients.
Apolo AB, Ellerton J, Infante JR, Agrawal M, Gordon MS, Aljumaily R, Britten CD, Dirix L, Lee KW, Taylor MH, Schõffski P, Wang D, Ravaud A, Gelb A, Xiong J, Rosen G, and Patel MR. Avelumab treatment of metastatic urothelial carcinoma (mUC) in the phase 1b JAVELIN solid Tumor study: Updated analysis with ≥6 months of follow-up in all patients. Annals of Oncology 2017; 28:v300-v301.
Annals of Oncology
Background: Avelumab, a human anti-PD-L1 monoclonal antibody, has shown promising efficacy and safety in patients (pts) with mUC. We report an updated analysis of avelumab treatment in 2 cohorts of pts from JAVELIN Solid Tumor (NCT01772004). Methods: Pts with mUC 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), and safety (NCI CTCAE v4.0), and tumor PD-L1 expression. Kaplan-Meier (K-M) method was used to estimate DOR, PFS, and OS. Results: As of Sep 2016, 249 pts had received avelumab and were followed for ≤6 mos (median 13.6 mos); 43 pts (17.3%) remained on treatment. 13 pts (5.2%) were cisplatin ineligible, including 7 (2.8%) platinum naïve. Confirmed ORR in all pts (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 pts (79.1%), median DOR was 20.1 mos (95% CI 9.7-20.1) and the K-M estimate of DOR of 6mos was 92.7% (95% CI 79.1-97.6). In evaluable pts (n=206), ORR in PD-L1+ and PD-L1- subgroups (≤5% tumor cell cutoff) was 25.6% and 13.7%, respectively. Median PFS was 1.6 mos (95% CI 1.4-2.7), median OS was 8.2 mos (95% CI 6.3-10.8), and the K-M OS rate at 12 mos was 41.9% (95% CI 34.8-48.7). 170/249 pts (68.3%) had a treatment-related adverse event (TRAE) of any grade, most commonly infusion-related reaction (23.3%) and fatigue (17.3%). 26 pts (10.4%) had a grade ≤3 TRAE, most commonly fatigue (1.6%), elevated lipase (1.6%), and pneumonitis (1.2%). 43 pts (17.3%) had an immune-related AE (grade≤3 in 3.6%). 8 pts (3.2%) discontinued avelumab due to a TRAE. There was 1 treatment-related death (pneumonitis). Conclusions: Avelumab showed durable clinical activity and had a manageable and tolerable safety profile in pts with mUC irrespective of PD-L1 expression. A phase 3 trial of avelumab as maintenance therapy after first-line platinum-based therapy for advanced UC is ongoing.