Nivolumab monotherapy in metastatic urothelial cancer (mUC): Updated efficacy by subgroups and safety results from the CheckMate 032 study

Abstract

Background: Nivolumab has shown promising efficacy and acceptable safety in an open‐label, multicenter phase I/II study in patients ( pts) with mUC after ≥1 prior platinum‐based therapy (NCT01928394). Here we report updated efficacy and safety results for the overall population based on additional follow‐up and outcomes by differing levels of PD‐L1 expression. Methods: Pts with mUC, unselected by PD‐L1 expression status, received nivolumab 3 mg/kg IV every 2 wk until progression or discontinuation. Pts who met protocol criteria could continue treatment beyond progression and cross over to nivolumab + ipilimumab. Tumor PD‐L1 membrane expression was assessed with Dako PD‐L1 immunohistochemical staining. Primary endpoint: objective response rate (ORR; RECIST 1.1); other endpoints: safety, progression‐free survival (PFS), overall survival (OS), and duration of response. Results: Of 78 treated pts (median age 65.5 years; range, 31‐85), 52 received ≥2 prior therapies. At a minimum follow‐up of 9 months, 23.1% of pts are on monotherapy and 23.1% switched to combination. Treatment discontinuation was mainly due to disease progression. PD‐L1 was evaluable in 67 pts (86%). Table shows overall efficacy. In pts with PD‐L1 expression ≥1% (n = 25) vs <1% (n = 42), ORR was 24% (95% CI, 9.4‐ 45.1) vs 26.2% (13.9‐42.0); median PFS, 5.5 mo (95% CI, 1.4‐11.2) vs 2.8 mo (1.4‐6.5). Grade 3 or 4 treatment‐related adverse events (TRAEs) occurred in 21.8% of pts; most frequent were ↑ lipase (5.1%), ↑ amylase (3.8%) and fatigue, ↓ neutrophils, rash, ↓ lymphocyte and dyspnea (2.6% each); grade 5 TRAEs occurred in 2.6% (pneumonitis and thrombocytopenia, 1 each). OS by PD‐L1 expression and additional subgroup analyses will be presented. Conclusions: Nivolumab showed encouraging efficacy and acceptable safety regardless of PD‐L1 expression in previously treated, unselected pts with mUC. (Table Presented).