ASCO 2018: Atezolizumab in First-Line Cisplatin-Ineligible or Platinum Treated Locally Advanced or Metastatic Urothelial Cancer: Long-Term Efficacy from Phase 2 Study IMvigor210

Chicago, IL (UroToday.com) Platinum-based chemotherapy is a standard first-line approach for patients with metastatic urothelial carcinoma, however many patients are ineligible for cisplatin. Over the last several years, encouraging survival outcomes for patients treated with immunotherapy has led to FDA approval of these agents. The IMvigor210 phase II trial, published two years ago, treated 310 patients with atezolizumab after progressing on first line platinum-based chemotherapy 1. Compared with a historical control objective response rate (ORR) of 10%, treatment with atezolizumab resulted in a significantly improved RECIST v1.1 ORR (15%, 95%CI 11-20, p=0·0058), as well as for each prespecified immune cell group: IC 2/3 - 27%, 95%CI 19-37, p<0·0001; IC1/2/3 - 18%, 95%CI 13-24, p=0·0004.Furthermore, over a median follow-up of 11.7 months (95%CI 11.4-12.2), ongoing responses were recorded in 38 (84%) of 45 responders. Last year, the IMvigor210 group reported results of atezolizumab as first-line treatment in 119 cisplatin-ineligible patients 2. At a median follow-up of 17.2 months, the ORR was 23% (95%CI 16-31%), the complete response rate (CRR) was 9%, and 19 of 27 responses were ongoing. Furthermore, the median PFS was 2.7 months (95%CI 2.1-4.2) and median OS was 15.9 months (95%CI 10.4-NR). Arjun Balar, MD, and colleagues presented updated follow-up for both cohorts in the IMvigor210 trial.

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:

Cohort 1: 
  • 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)
Cohort 2:
  • 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)
The updated follow-up of the important IMvigor210 phase II trial demonstrate durable and encouraging responses among this comorbid population with few treatment alternatives. Balar concluded with several important take-home points:

  • 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). 
Clinical trial information: NCT02951767 and NCT02108652

References:
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
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