(UroToday.com) The 2023 GU ASCO annual meeting included an oral abstract session on urothelial carcinoma, featuring a presentation by Dr. Aristotelis Bamias discussing final OS analysis of atezolizumab monotherapy vs chemotherapy in untreated locally advanced or metastatic urothelial carcinoma from the phase 3 IMvigor130 study. Two interim OS analyses from IMvigor130 demonstrated non-statistically significant OS benefit with atezolizumab monotherapy (Arm B) vs placebo + platinum (investigator choice of carboplatin or cisplatin)/gemcitabine (platinum/gemcitabine; Arm C) in patients with PD-L1–high (IC2/3) metastatic urothelial carcinoma, as well as a favorable safety profile vs chemotherapy.1 Exploratory data showed clinical benefit with atezolizumab monotherapy in cisplatin-ineligible patients with IC2/3 tumors. At the 2023 GU ASCO annual meeting, Dr. Bamias and colleagues reported the final OS analysis from IMvigor130 Arms B and C.
Patients were randomly assigned 1:1:1 to Arm A (atezolizumab + platinum/gemcitabine; not reported here), B or C. Due to the statistical testing hierarchy, no formal comparison of OS (co-primary endpoint) in Arm B vs C was performed in ITT and IC2/3 patients:
ORR and duration of response, both per investigator-assessed RECIST 1.1 (secondary endpoints), and safety were assessed. Subgroup analyses of OS in cisplatin-ineligible patients and disease control rate (confirmed complete response, partial response or [stable disease ≥6 months]) were exploratory.
As of the data cutoff of August 31, 2022, time since last patient randomly assigned was 49 month. The final disposition of patients included 7% of patients alive and on treatment in Arm B and 4% of patients in Arm C:
OS data did not show benefit for ITT patients for Arm B vs Arm C (HR 0.98, 95% CI 0.82, 1.16):
In the ITT population, the 24-month OS rates were 34% in Arm B and 32% in Arm C. With regards to next subsequent therapy, 46% of patients in Arm B and 47% of patients in Arm C received a next line of therapy:
In the cisplatin-ineligible IC2/3 subgroup, patients in Arm B had significantly improved OS compared to those in Arm C (HR 0.56, 95% 0.34, 0.91):
ORR was 24.2% (87/359; 38% disease control rate) in Arm B and 44.4% (158/356; 59% disease control rate) in Arm C; median duration of response was 29.6 and 8.1 months, respectively. In cisplatin-ineligible IC2/3 patients, ORR was 40.0% (20/50) in Arm B and 32.6% (14/43) in Arm C, which median duration of response was not evaluable in Arm B and 6.2 months in Arm C:
Of safety-evaluable patients, 57 of 354 in Arm B (16%) and 312 of 389 in Arm C (80%) had a grade 3/4 treatment-related adverse event; 3 (1%) and 4 (1%), respectively, had a grade 5 treatment-related adverse event. Grade 3/4 adverse events of special interest occurred in 36 patients (10%) in Arm B and 17 (4%) in Arm C.
Dr. Bamias concluded his presentation discussing final OS analysis of atezolizumab monotherapy vs chemotherapy in untreated locally advanced or metastatic urothelial carcinoma from the phase 3 IMvigor130 study with the following take-home messages:
- Data from the final OS analysis of the IMvigor130 study of first-line atezolizumab in metastatic urothelial carcinoma was consistent with finding from the first and second interim OS analyses
- Atezolizumab monotherapy continued to show better tolerability vs chemotherapy with no new safety concerns
- These exploratory data support the benefit-risk ratio of atezolizumab monotherapy vs chemotherapy for first-line cisplatin-ineligible IC2/3 metastatic urothelial carcinoma
Clinical trial information: NCT02807636
Presented by: Aristotelis Bamias, MD, National and Kapodistrian University of Athens, Athens, Greece
Co-Authors: Ian D. Davis, Matt D. Galsky, Jose Angel Arranz Arija, Eiji Kikuchi, Enrique Grande, Xavier Garcia del Muro, Se Hoon Park, Ugo De Giorgi, Boris Alekseev, Marina Mencinger, Kouji Izumi, Javier Puente, Jian-Ri Li, Fabiola Bene-Tchaleu, Sanjeev Mariathasan, Chooi Peng Lee, Sandrine Bernhard, Maria De Santis
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, @zklaassen_md on Twitter during the 2023 Genitourinary (GU) American Society of Clinical Oncology (ASCO) Annual Meeting, San Francisco, Thurs, Feb 16 – Sat, Feb 18, 2023.
References:
- 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.