For the purposes of this updated analysis, the authors defined the cohorts as follows:
- Cohort 1 (n=119) as patients who were treatment naive for metastatic urothelial carcinoma, had an ECOG performance status ≤ 2, and were ineligible for cisplatin by at least one of the following criteria: GFR > 30 and < 60 mL/min, ≥ G2 hearing loss or peripheral neuropathy or ECOG performance status 2.
- Cohort 2 (n=310) as patients progressed after platinum-based chemotherapy and had ECOG performance status ≤ 1 and GFR ≥ 30 mL/min. Atezolizumab 1200 mg IV was given every three weeks until disease progression (Cohort 1) or loss of clinical benefit (Cohort 2). The following endpoints were evaluated: RECIST v1.1 ORR by central review, duration of response, and OS.
The median follow-up for Cohort 1 was 29 months, and 33 months for Cohort 2. In Cohort 1, the ORR was 24% (95%CI 16-32), CRR was 8%, and median duration of response was not reached (95%CI 30.4 months to NR; 19 of 28 responses ongoing). In patients in Cohort 1 ≥ 80 years of age (n=25), the ORR was 28% (95%CI 12-49), and CRR was 12%. In Cohort 2, the ORR was 16% (95%CI 13-21), CRR was 7%, and median duration of response was 24.8 months (95%CI 13.8-30.4). Interestingly, in both cohorts, sustained responses occurred among patients who discontinued atezolizumab for reasons besides disease progression. Survival outcomes were as follows:
- Median OS 16.3 months (95%CI 10.4-24.5)
- 1-year OS 58% (95%CI 49-67)
- 2-year OS 41% (95%CI 32-50)
- Median OS 7.9 months (95%CI 6.7-9.3)
- 1-year OS 37% (95%CI 31-42)
- 2-year OS 23% (95%CI 19-28)
- With > 2 y median follow-up, responses to first-line atezolizumab in cisplatin-ineligible metastatic urothelial carcinoma patients, including patients ≥ 80 years of age, appeared durable, resulting in continued improvement in OS since the primary analysis.
- For pre-treated patients, ORR and OS were in line with prior data and taken together with the duration of response, data were consistent with Phase 3 results (IMvigor211 3).
1. Rosenberg JE, Hoffman-Censits J, Powles T, et al. Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: A single-arm, multicentre, phase 2 trial. Lancet 2016;387(10031):1909-1920.
2. Balar AV, Galsky MD, Rosenberg JE, et al. Atezolizumab as first-line treatment in cisplatin-ineligible patients with locally advanced and metastatic urothelial carcinoma: A single-arm, multicentre, phase 2 trial. Lancet 2017;389(10064):67-76.
3. Powles T, Duran I, van der Heijden MS, et al. Atezolizumab versus chemotherapy in patients with platinum-treated locally advanced or metastatic urothelial carcinoma (IMvigor211): A multicentre, open-label, phase 3 randomized controlled trial. Lancet 2018;391:748-757.
Presented by: Arjun Vasant Balar, MD, Laura and Isaac Perlmutter Cancer Center, NYU Langone Medical Center, New York, NY
Co-Authors: Robert Dreicer, Yohann Loriot, Jose Luis Perez-Gracia, Jean H. Hoffman-Censits, Daniel Peter Petrylak, Michiel Simon Van Der Heijden, Beiying Ding, Xiaodong Shen, Jonathan E. Rosenberg; Laura and Isaac Perlmutter Cancer Center, NYU Langone Medical Center, New York, NY; University of Virginia Emily Couric Clinical Cancer Center, Charlottesville, VA; Gustave Roussy, Villejuif, France; Clinica Universidad de Navarra, Pamplona, Spain; John Hopkins University Sidney Kimmel Cancer Center, Baltimore, MD; Yale School of Medicine, New Haven, CT; Department of Medical Oncology, The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam, Netherlands; Genentech, Inc., South San Francisco, CA; Memorial Sloan Kettering Cancer Center, New York, NY
Written by: Zachary Klaassen, MD, Urologic Oncology Fellow, University of Toronto, Princess Margaret Cancer Centre, Twitter: @zklaassen_md at the 2018 ASCO Annual Meeting - June 1-5, 2018 – Chicago, IL USA