ASCO GU 2021: Atezolizumab Monotherapy vs Chemotherapy in Previously Untreated Locally Advanced or Metastatic Urothelial Carcinoma: Clinical Outcomes by PD-L1 Status In Cisplatin-Ineligible Patients From the Phase III IMvigor130 Study

In IMvigor130, patients were randomized 1:1:1 to Arms A, B or C.² The trial schema for IMvigor130 is as follows:

Evaluation of overall survival (co-primary endpoint) was performed via a hierarchical fixed sequence procedure: Arm A versus Arm C in the intention to treat population; then, Arm B versus Arm C in the intention to treat population and IC2/3 patients. No formal testing was performed in this exploratory subgroup analyses. Overall survival and RECIST 1.1 objective response rate (per investigator, a secondary end point) were descriptively evaluated.

There was no difference in overall survival comparing atezolizumab (Arm B) versus placebo plus platinum/gemcitabine (Arm C) in the intention to treat population (HR 1.02, 95% CI 0.83-1.24). Similarly, there was no survival benefit comparing Arm B versus Arm C in PD-L1 IC2/3 patients (HR 0.68, 95% CI 0.43-1.08), however there was an overall survival (Arm B versus Arm C: HR 0.53, 95% CI 0.30-0.94) and objective response benefit (Arm B 38%, 95% CI 25-53; Arm C 33%, 95% CI 19-49) in atezolizumab-treated cisplatin-ineligible IC2/3 patients:

In the overall safety population, all-grade treatment-related adverse events had occurred in 60% of Arm B and 96% of Arm C patients. Grade 3-4 treatment-related adverse events occurred in 15% of Arm B and 81% of Arm C patients. 

Dr. Galsky concluded this exploratory analysis of the IMvigor130 trial with the following take home messages:

• Many patients with metastatic urothelial carcinoma are ineligible for first-line cisplatin-based chemotherapy and are in need of other treatment options
• IMvigor130 showed significant benefit and encouraging interim overall survival data favoring atezolizumab plus platinum/gemcitabine versus placebo plus platinum/gemcitabine as first-line treatment for metastatic urothelial carcinoma in the intention to treat population (Arm A versus Arm C) were observed
• In this exploratory study, results suggested improved overall survival with atezolizumab monotherapy versus placebo plus platinum/gemcitabine in cisplatin-ineligible patients with IC2/3 status, and objective response rates were higher in with atezolizumab in this subgroup
• Together with atezolizumab’s better tolerability profile relative to chemotherapy, these results provide additional evidence of clinical benefit with atezolizumab monotherapy in patients with first-line cisplatin-ineligible IC2/3 metastatic urothelial carcinoma

Presented by: Matthew Galsky, MD, Director of Genitourinary Medical Oncology, Tisch Cancer Institute, Professor of Medicine, Mount Sinai

Co-Authors: Aristotelis Bamias, Jose Angel Arranz Arija, Ian D. Davis, Maria De Santis, Eiji Kikuchi, Xavier Garcia del Muro, Se Hoon Park, Ugo De Giorgi, Boris Alekseev, Marina Mencinger, Kouji Izumi, Javier Puente, Jian-Ri Li, Almut Mecke, Sanjeev Mariathasan, Romain Banchereau, Xinhui Huang, Chooi Peng Lee, Enrique Grande; Icahn School of Medicine at Mount Sinai/Tisch Cancer Institute, New York, NY; National and Kapodistrian University of Athens, Athens, Greece; Gregorio Marañón Hospital, Madrid, Spain; Eastern Health Clinical School, Monash University, Box Hill, VIC, Australia; Department of Urology, Charité University Hospital, Berlin, Germany and Department of Urology, Medical University of Vienna, Vienna, Austria; St. Marianna University School of Medicine, Kawasaki, Japan; Catalan Institute of Oncology, IDIBELL, University of Barcelona, Barcelona, Spain; Samsung Medical Center, Seoul, South Korea; Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST), IRCCS, Meldola, Italy; Research Oncology Institute, Tomsk, Russian Federation; Institute of Oncology Ljubljana, Ljubljana, Slovenia; Kanazawa University Hospital, Kanazawa, Japan; Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), CIBERONC, Madrid, Spain; Taichung Veterans General Hospital, Taichung, Taiwan; F. Hoffmann-La Roche Ltd., Basel, Switzerland; Genentech, Inc., South San Francisco, CA; Roche Products Limited, Welwyn Garden City, United Kingdom; MD Anderson Cancer Center Madrid, Madrid, Spain

References:

1. 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.
2. Galsky MD, Arranz Arija JA, Bamias A, et al. Atezolizumab with or without chemotherapy in metastatic urothelial cancer (IMvigor130): A multicentre, randomized, placebo-controlled phase 3 trial. Lancet. 2020 May 16;395(10236):1547-1557.