Safety and efficacy of atezolizumab (atezo) for locally advanced or metastatic urothelial or non-urothelial urinary tract carcinoma: Subgroup analyses of the international SAUL study according to PD-L1 status and age

Introduction and Objectives: The monoclonal antibody atezo, which targets PD-L1, is an approved therapy for locally advanced/metastatic urothelial carcinoma based on results from the IMvigor210 and IMvigor211 phase 2 and 3 trials. The single-arm SAUL study (NCT02928406) in a broader patient (pt) population demonstrated median overall survival (OS) of 8.7 months; safety was consistent with previous atezo trials [Sternberg, Eur Urol 2019]. We report prespecified analyses of efficacy and safety according to PD-L1 status and age.

Materials and methods: Eligible pts had locally advanced/metastatic urothelial or non-urothelial urinary tract carcinoma; pts with renal impairment, ECOG PS 2, treated asymptomatic CNS metastases, stable controlled autoimmune disease, concomitant steroids, HIV, or non-urothelial histology (excluded from IMvigor211) were eligible for SAUL. Pts received atezo 1200 mg q3w until loss of clinical benefit or unacceptable toxicity. Safety was the primary endpoint; OS and overall response rate (ORR) were secondary endpoints. Predefined subgroup analyses included outcomes according to PD-L1 status (assessed by VENTANA SP142) and age.

Results: Of 1004 pts enrolled Nov 2016–Mar 2018, 997 received atezo. PD-L1 status was IC0/1 in 66% and IC2/3 in 27% (unknown in 7%). The table summarises efficacy and safety.

Conclusions: Atezo was effective and well tolerated across both IC subgroups. OS and ORR appear enhanced in the PD-L1 IC2/3 subgroup (overall and in IMvigor211-like pts). There was no evidence of increased toxicity or reduced efficacy in older pts.