1. Atezolizumab monotherapy for metastatic urothelial carcinoma: final analysis from the phase II IMvigor210 trial.
- Author
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Rosenberg, J, Galsky, M, Powles, T, Petrylak, D, Bellmunt, J, Loriot, Y, Necchi, A, Hoffman-Censits, J, Perez-Gracia, J, van der Heijden, M, Dreicer, R, Durán, I, Castellano, D, Drakaki, Alexandra, Retz, M, Sridhar, S, Grivas, P, Yu, E, ODonnell, P, Burris, H, Mariathasan, S, Shi, Y, Goluboff, E, and Bajorin, D
- Subjects
PD-L1-high ,checkpoint inhibitor ,cisplatin-ineligible ,long-term survival ,metastatic urothelial carcinoma ,platinum-refractory ,Humans ,Antibodies ,Monoclonal ,Humanized ,Male ,Female ,Aged ,Middle Aged ,Aged ,80 and over ,Carcinoma ,Transitional Cell ,Urologic Neoplasms ,Adult ,B7-H1 Antigen ,Treatment Outcome - Abstract
BACKGROUND: The IMvigor210 trial demonstrated clinical benefit and manageable toxicity with atezolizumab monotherapy [anti-programmed death-ligand 1 (PD-L1)] in patients with metastatic urothelial carcinoma (UC) in primary analyses. Final efficacy and safety results after long-term follow-up are reported. PATIENTS AND METHODS: This phase II single-arm trial of atezolizumab monotherapy in patients with advanced UC included two cohorts: untreated patients ineligible for cisplatin-based chemotherapy (cohort 1; n = 119) and those previously treated with platinum-based chemotherapy (cohort 2; n = 310). Atezolizumab was administered i.v. (1200 mg every 21 days) until progression or unacceptable toxicity. Primary endpoints were independent review facility-assessed confirmed objective response rate (ORR) per RECIST 1.1 in cohort 1 and independent review facility-assessed ORR per RECIST 1.1 and investigator-assessed modified (m)RECIST in cohort 2. Overall survival (OS), efficacy by PD-L1 status, and safety were also assessed. RESULTS: At data cut-off (1 June 2023), the median survival follow-up was 96.4 months (range, 0.2-103.4 months) in cohort 1 and 46.2 months [0.2 (censored)-54.9 months] in cohort 2. In cohort 1, the ORR [95% confidence interval (CI)] was 23.5% (16.2% to 32.2%) in all patients and 28.1% (13.8% to 46.8%) in the PD-L1 tumor-infiltrating immune cell (IC)2/3 subgroup. Median OS (95% CI) was 16.3 months (10.4-24.5 months) overall and 12.3 months (6.0-49.8 months) in the PD-L1 IC2/3 subgroup. In cohort 2, the ORR (95% CI) was 16.5% (12.5% to 21.1%) per RECIST 1.1 and 19.7% (95% CI 15.4% to 24.6%) per mRECIST in all patients and 27.0% (18.6% to 36.8%) and 28.0% (19.5% to 37.9%), respectively, in the PD-L1 IC2/3 subgroup. Median OS (95% CI) was 7.9 months (6.7-9.3 months) in all patients and 11.9 months (9.0-22.8 months) in the IC2/3 subgroup. Treatment-related grade 3/4 adverse events occurred in 21.8% (cohort 1) and 18.7% (cohort 2); one treatment-related death occurred in cohort 1. CONCLUSIONS: With long-term follow-up, atezolizumab monotherapy demonstrated clinically meaningful efficacy with durable responses in a subset of patients with metastatic UC; there were no new safety signals.
- Published
- 2024