This phase III, open-label, multicenter, randomized, controlled trial - IMvigor010 is designed to evaluate the efficacy and safety of adjuvant atezolizumab vs. observation in patients with muscle-invasive bladder or upper-tract UC (UTUC) who are at high risk of recurrence following cystectomy.
This trial is enrolling patients with histologically confirmed muscle-invasive UC of the bladder, renal pelvis or ureters. Eligible patients must have an ECOG performance status of 0-2 and an evaluable sample for PD-L1 immunohistochemical testing. All patients are required to undergo complete surgical resection with lymph node dissection (either radical cystectomy or nephroureterectomy) and have negative surgical margins (except for carcinoma in situ at distal ureteral/urethral margin).
Patients who received NAC, tumor pathological stage must be pT2-T4a or pN+. Patients not treated with NAC must also be ineligible for or have declined cisplatin-based AC, with tumor pathological stage of pT3-T4a or pN+. Post-surgical AC or radiation are not permitted. For patients with UTUC, post-surgical topical chemotherapy or BCG are not permitted as well. Additional Exclusion criteria include history of autoimmune disease or active pneumonitis, significant cardiovascular disease within previous 3 months, severe infection during the 4 weeks before Atezolizumab initiation and positive HIV and/or active hepatitis B or C or tuberculosis.
The trial is currently enrolling and randomizing patients 1:1 to observation or atezolizumab (1200 mg IV every 3 weeks) as adjuvant treatment for 16 cycles or 1 y (whichever occurs first). The trial goal is to recruit approximately 700 patients. The primary efficacy endpoint is disease-free survival. Secondary efficacy endpoints include overall survival, disease-specific survival, distant metastasis–free survival and non–urinary tract recurrence-free survival.
Safety, pharmacokinetics and patient-reported outcomes will also be assessed. Exploratory analyses will assess predictive, prognostic and pharmacodynamic biomarkers. Stratification factors include number of lymph nodes resected (< 10 vs ≥ 10), nodal status (positive vs negative), tumor stage after resection (≤ pT2 vs pT3/pT4), PD-L1 status (IC0/1 vs IC2/3) and prior NAC (yes vs no). Disease recurrence will be assessed based on radiographic evidence and available biopsy results.
Presented by: Gschwend J., Bellmunt J., Castellano D., Daneshmand S., Hussain M., Nishiyama H.6, Powles T., Degaonkar V., Nguyen Duc A., Culine S
Written by: Hanan Goldberg, MD, Urologic Oncology Fellow (SUO), University of Toronto
at the #EAU17 -March 24-28, 2017- London, England