ASCO GU 2023: Atezolizumab + Platinum/gemcitabine vs Placebo + Platinum/Gemcitabine for First-Line Treatment of Locally Advanced or Metastatic Urothelial Carcinoma: Final OS from the Randomized Phase 3 IMvigor130 Study

(UroToday.com) The 2023 GU ASCO annual meeting included an oral abstract session on urothelial carcinoma, featuring a presentation by Dr. Enrique Grande discussing final OS results from the randomized phase 3 IMvigor130 study, assessing atezolizumab + platinum/gemcitabine vs placebo + platinum/gemcitabine for first-line treatment of locally advanced or metastatic urothelial carcinoma. The IMvigor130 primary analysis demonstrated statistically significant PFS benefit with first line atezolizumab + platinum/gemcitabine (Arm A) vs placebo + platinum/gemcitabine (Arm C) in patients with metastatic urothelial carcinoma.¹ Interim data showed improved OS with Arm A vs C but did not cross the pre-specified threshold for significance.^1,2 In exploratory analyses, OS improved when atezolizumab was combined with cisplatin vs carboplatin regardless of PD-L1 status. At the 2023 GU ASCO annual meeting, Dr. Grande and colleagues report final OS data from Arms A and C.

Patients were randomly assigned 1:1:1 to Arms A, B (atezolizumab alone), or C. Arm A and C patients received cisplatin or carboplatin per investigator choice. Co-primary endpoints were PFS per investigator RECIST 1.1 and OS (Arm A vs C), and OS (Arm B vs C), tested hierarchically:

Safety, ORR and duration of response, disease control rate (confirmed complete response, partial response, or [stable disease ≥ 6 months]), and pre-specified exploratory OS data are also reported. With regards to disposition of patients, 7% of patients in Arm A were alive and on treatment, compared to 3% of patients in Arm C:

As of the data cutoff of August 31, 2022 (49 months since the last patient was randomly assigned), in ITT patients, OS benefit was not statistically significant in the cisplatin subgroup (HR 0.85, 95% CI 0.73, 1.00):

Subsequent non-protocol therapies were received by 33% of patients in Arm A and 47% of patients in Arm C:

OS by clinical subgroup showed some benefit for subgroups, however, most of the 95% confidence intervals crossed the threshold of 1.00:

When looking at OS by choice of platinum chemotherapy, again there was no benefit whether patients received cisplatin (HR 0.76, 95% CI 0.57, 1.01) or carboplatin (HR 0.89, 95% CI 0.74, 1.08). Similar results were also reported if patients received cisplatin and had PD-L1 expression (HR 0.74, 95% CI 0.39, 1.38) or no PD-L1 expression (HR 0.75, 95% CI 0.55, 1.03). In ITT patients, disease control rate was 64.9% (290/447) in Arm A and 60.2% (239/397) in Arm C:

With regards to safety, 81% of safety-evaluable patients (370/454) in Arm A and 80% (312/389) in Arm C had a grade 3/4 treated-related adverse events, whereas grade 5 treated-related adverse events occurred in 9 patients (2%) in Arm A and 4 (1%) in Arm C. Grade 3/4 adverse events of special interest were seen in 41 patients (9%) in Arm A and 17 (4%) in Arm C.

Dr. Grande concluded his presentation discussing final OS results from the randomized phase 3 IMvigor130 study with the following take-home messages:

• In this final analysis, improved OS with atezolizumab + platinum/gemcitabine vs placebo + platinum/gemcitabine did not reach statistical significance in ITT patients with metastatic urothelial carcinoma
• As seen with prior exploratory data, improved OS with atezolizumab + platinum/gemcitabine was greater when patients received cisplatin vs carboplatin
• The safety profile of atezolizumab + platinum/gemcitabine remained consistent with that of each agent
• Efficacy and safety results from the final OS analysis are consistent with the first and second interim OS analyses

Clinical trial information: NCT02807636 

Presented by: Enrique Grande, MD, PhD, Msc, MD Anderson Cancer Center, Madrid, Spain

Co-Authors: Matt D. Galsky, Jose Angel Arranz Arija, Maria De Santis, Ian D. Davis, Aristotelis Bamias, Eiji Kikuchi, Xavier Garcia del Muro, Se Hoon Park, Ugo De Giorgi, Boris Alekseev, Marina Mencinger, Kouji Izumi, Javier Puente, Jian-Ri Li, Peter H. O'Donnell, Sandrine Bernhard, Chooi Peng Lee, Fabiola Bene-Tchaleu, Sanjeev Mariathasan

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:

1. 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.
2. Galsky MD, Arranz JA Grande E, et al. Atezolizumab (atezo) + platinum/gemcitabine (plt/gem) vs placebo + plt/gem in patients (pts) with previously untreated locally advanced or metastatic urothelial carcinoma (mUC): Updated overall survival (OS) from the randomized phase III study IMvigor130. Cancer Res. 2021;81(13_suppl): CT042.