Status:
Open
Clinicaltrials.gov identifier:
Sponsor:
F Hoffmann-La Roche/Genentech
Enrollment:
809
Study Design:
IMvigor010 was a multicenter international open-label, randomized, phase 3 trial for patients after radical cystectomy or nephroureterectomy with lymph node dissection. Patients had ypT2-4a or ypN+ tumors following neoadjuvant chemotherapy or pT3-4a or pN+ tumors if no neoadjuvant chemotherapy was received. Patients not treated with neoadjuvant chemotherapy were required to be cisplatin ineligible or declined cisplatin-based adjuvant chemotherapy. Patients were randomized (1:1) to atezolizumab anti PD-L1 immunotherapy IV every 3 weeks for 1 year vs. observation. Randomization was stratified by previous neoadjuvant chemotherapy use, number of lymph nodes resected, pathological nodal status, tumor stage, and PD-L1 expression on tumor-infiltrating immune cells.
Rationale:
As mentioned earlier in the nivolumab aduvant trial, despite standard curative-intent treatment with neoadjuvant cisplatin-based chemotherapy, followed by radical surgery in eligible patients, muscle-invasive urothelial carcinoma has a high recurrence rate and there is not enough clincal trial evidence supporting adjuvant therapy. This trial aimed to evaluate atezolizumab as adjuvant therapy in patients with high-risk MIUC.
Endpoints:
The primary endpoint was disease-free survival in the ITT population.
Comments:
IMvigor010 was the first-completed phase 3 adjuvant study to evaluate the role of a checkpoint inhibitor in MIUC. The trial did not meet its primary endpoint of improved DFS in the atezolizumab group compared to observation. Atezolizumab was generally tolerable, with no new safety signals; however, higher frequencies of adverse events leading to discontinuation were reported than in metastatic urothelial carcinoma studies. These data do not support the use of adjuvant atezolizumab therapy in MIUC. The results differ from those in the nivolumab study. There were more patients who discontinued therapy in this study and the reasons for the differences between the two trials require further exploration.
Results:
406 patients were assigned to the atezolizumab group and 403 were assigned to observation. Median follow-up was 21.9 months (IQR 13.2-29.8). Median DFS was 19.4 months (95% CI 15.9-24.8) with atezolizumab and 16.6 months (11.2-24.8) with observation (stratified hazard ratio 0.89 [95% CI 0.74-1.08]; p=0.24).
