Status:
Open
Clinicaltrials.gov identifier:
Sponsor:
Hoffmann-La Roche
Primary Investigator(s):
Study Director: Clinical Trials Hoffmann-La Roche
Enrollment:
439
Study Design:
Phase II, single arm multi-center trial of atezolizumab in patients with locally advanced or metastatic urothelial bladder cancer. Two cohorts were planned: Cohort 1 consisted of 119 treatment naïve patients who were cisplatin ineligible and Cohort 2 consisted of patients who had progressed during or following platinum therapy (see below). The results of cohort 1 were presented at the ASCO meeting for the first time (Balar AV et al).
The primary endpoint was objective response rate (ORR) and the secondary endpoints were duration of response, progression-free survival (PFS), overall survival (OS), and the incidence of adverse events.
Rationale:
PD-L1 checkpoint blockade has recently received FDA approval for metastatic urothelial cancer refractory to standard chemotherapy and the results of Cohort 1 are exciting because this is the use of such therapy as upfront therapy for locally advanced or metastatic urothelial bladder cancer in patients who are ineligible for cisplatin-based chemotherapy.
Comments:
This is the first study to present atezolizumab as upfront therapy for urothelial cancer. The results are encouraging for the use of checkpoint blockade inhibitors as first line therapy, especially in patients unfit for cisplatin.
Results:
Most patients were ineligible due to renal impairment. Median follow-up for patients was 14.4 months with ORR of 24% , and responses we seen in all PDL-1 IC subgroups. Responders included patients with poor baseline prognostic factors. Median overall survival was 14.8 months. Severe adverse events were noted in 10–15% of patients including hypothyroidism, liver function abnormalities, rash, and diarrhea, with a low rate of Garde 3-4 side effects.
