Status:
Open
Clinicaltrials.gov identifier:
Sponsor:
SWOG/NRG (National Cancer Institute), Genentech
Enrollment:
475
Study Design:
This is a randomized trial for patients with localized muscle-invasive bladder cancer T2-4N0M0 who have refused or are unfit for radical cystectomy or preferentially choose bladder sparing treatment whereby patients are randomized to radiation therapy (three-dimensional conformal or intensity-modulated) with chemotherapy as per the treating physician with or without atezolizumab. The chemotherapy can consist of either gemcitabine, cisplatin, or fluorouracil and mitomycin. Patients treated in the atezolizumab arm are treated every 3 weeks for up to 6 months.
Rationale:
Chemoradiation has an established therapeutic role in localized muscle-invasive bladder cancer. This cooperative group trial tests the hypothesis that the addition of immunotherapy, specifically atezolizumab, improves bladder intact event-free survival.
Endpoints:
The primary outcome is bladder intact event-free survival (BI-EFS) rate from the date of randomization to the first documentation of a BI-EFS event, assessed up to 5 years.
This composite endpoint includes the absence of muscle invasive bladder recurrence, regional pelvic soft tissue or nodal recurrence, distant metastases, bladder cancer or toxicity related death or cystectomy. Secondary endpoints include: overall survival at 5 years, disease-specific survival, NMIBC recurrence rate, cystectomy rate, and several immunologic and biologic endpoints.
Comments:
This is an ongoing trial with a target enrollment of 475 patients. As of July 1,2021 172 patients have been registered with a target enrollment of 10 patients per month. The DSMC considered it safe to continue the trial, though it is surprising that there were more grade 3 or high toxicity events in the immunotherapy arm that were deemed not to be immune-related. This suggests that combination therapy may result in a higher number of toxicities that are a result more of combination treatment as opposed to being related to immunotherapy alone.
Results:
At GU ASCO 2021, safety data were reported for the first 73 patients enrolled on trial. The atezolizumab arm contained 37 patients while the trimodal therapy arm contained 36 patients. Overall, the immunotherapy arm had 23 grade 3 or higher toxicity rates compared to 11 in the trimodal therapy alone arm. Moreover, none of the toxicities were deemed to be immune-related. The most common toxicity was hematological (anemia, lymphopenia and decreased WBC).
