ESMO 2017: Atezolizumab in Platinum-Treated Locally Advanced or Metastatic Urothelial Carcinoma: Post-Progression Outcomes from the Phase 2 IMvigor210 Study

Madrid, Spain (UroToday.com) At today’s poster discussion session at ESMO 2017, Dr. Necchi and colleagues presented results from their study assessing atezolizumab in platinum-treated locally advanced or metastatic urothelial carcinoma. Certainly, there are few adequate treatment options for metastatic urothelial carcinoma, which portends a poor overall survival (OS). The IMvigor210 trial demonstrated efficacy and safety of atezolizumab (anti–PD-L1) in metastatic urothelial carcinoma [1], leading to approval in the US and abroad. The objective of the current study was to evaluate outcomes in platinum-treated IMvigor210 patients treated with atezolizumab beyond disease progression.

IMvigor210 was a phase II trial that enrolled patients with metastatic urothelial carcinoma that progressed during or following platinum based chemotherapy. Atezolizumab was given 1200 mg IV q3w until loss of clinical benefit per investigator. For the purposes of this study, a post hoc analysis (with follow-up through July 2016) was performed, assessing (i) on-study RECIST v1.1 response (pre– and post–first progressive disease; central review), (ii) sum of target lesion diameters (% change from progressive disease), (iii) OS, and (iv) post-progression OS. There were 220 patients who experienced progressive disease (among 310 in study) that were evaluable. This included 137 patients who continued atezolizumab post-progressive disease, and 83 patients who received other (n = 19) or no (n = 64) systemic therapy. Patients who continued atezolizumab had fewer poor prognostic factors. Pre-progressive disease treatment duration was similar in patients who did or did not continue atezolizumab post-progressive disease (median 1.5 and 1.4 months, respectively), and median post-progressive atezolizumab duration was 1.6 months. Patients continuing atezolizumab beyond progressive disease had higher pre-progressive disease objective response rate vs other groups. There were 45 patients (42%) who continued atezolizumab following initial progressive disease (of 108 with post–first progressive disease measurements) who experienced decreases in sum of target lesion diameters. Median OS for those continuing atezolizumab beyond progressive disease was 12.8 months, compared to 3.6 months for those not treated with atezolizumab beyond progressive disease.

In conclusion, patients who continued atezolizumab beyond progressive disease derived prolonged clinical benefit including tumor burden reduction and longer OS compared to patients who discontinued atezolizumab post-progressive disease. As Dr. Necchi notes, an important future challenge in the post-progressive disease setting will be to identify patients most likely to respond to atezolizumab and appropriate sequencing of chemotherapy agents thereafter.

Speaker: Andrea Necchi, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy

Co-Authors: R. W. Joseph (Jacksonville, United States of America) Y. Loriot (Villejuif, France)
J. Hoffman-Censits (Philadelphia, United States of America) J. Perez Gracia (Pamplona, Spain)
D. P. Petrylak (New Haven, United States of America) Q. Zhu (South San Francisco, United States of America) B. Ding (South San Francisco, United States of America) C. Kaiser (South San Francisco, United States of America) J. E. Rosenberg (New York, United States of America)

Written By: Zachary Klaassen, MD, Urologic Oncology Fellow, University of Toronto, Princess Margaret Cancer Centre, Twitter: @zklaassen_md at the European Society for Medical Oncology Annual Congress - September 8 - 12, 2017 - Madrid, Spain

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.
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