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. Also as part of the IMvigor210 trial was a cohort of patients (n=119) that were treated with atezolizumab as first-line treatment secondary to being cisplatin-ineligible 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). Prior to FDA approval of atezolizumab, the US expanded access program granted metastatic urothelial carcinoma patients access to atezolizumab, which included patients previously ineligible for IMvigor210 3. At ASCO 2018 annual meeting, Dr. Hoffman-Censits presented results of patients with impaired baseline renal function or variant histology that received atezolizumab as part of the US extended access program.
For this study, 114 patients with metastatic urothelial carcinoma were enrolled if they had progressed during or following platinum-based chemotherapy and had an ECOG performance status ≤ 2. These patients had predominant urothelial histology, but no restrictions on creatinine clearance levels (initially, enrollment excluded patients with a significant renal disorder requiring dialysis, but was later amended such that these patients were eligible). Patients received atezolizumab 1200 mg IV every three weeks until loss of clinical benefit. The primary outcomes were ORR (per investigator), disease control rate [complete response (CR) + partial response (PR) + stable disease (SD)], and safety, assessed by creatinine clearance or primary tumor histology.
There were 218 previous platinum-treated patients with metastatic urothelial carcinoma enrolled, and 214 were treated with atezolizumab. This included 114 patients with evaluable data, of which the following responses were noted over a median follow-up of 2.3 months (range 1.6-3.4 months):
All-grade treatment-related AEs occurred in 46% of patients, and in the renal function subgroups, treatment-related AE rates ranged from 35% (creatinine clearance 30-45 mL/min) to 54% (creatinine clearance 45-60 mL/min). Furthermore, there were no treatment-related AE rate differences by histology noted (46% for both urothelial only and mixed histology). Importantly, treatment-related AEs leading to discontinuation of therapy were uncommon (< 3% across subgroups).
Patients enrolled in clinical trials are often the fittest and most likely to derive a treatment benefit. The advantage of studies assessing outcomes among patients receiving therapy through extended access programs is that results for patients not typically eligible for trials (herein patients with poor renal function or variant histology) are evaluable. A limitation of the analysis is that minor differences between subgroups were not controlled for and further analyses in larger populations is warranted. Dr. Hoffman-Censits concluded that, based on these results, responses or stable disease with atezolizumab were seen in patients with mixed histology or compromised renal function (notably in patients with creatinine clearance 30-45 mL/min), and safety was comparable across subgroups. Furthermore, Dr. Hoffman-Censits highlights that these results suggest that atezolizumab provides clinical benefit across a broad range of previous platinum-treated metastatic urothelial cancer patients.
Clinical trial information: NCT02589717
Presented By: Jean H. Hoffman-Censits, John Hopkins University Sidney Kimmel Cancer Center, Baltimore, MD
Co-Authors: Sumanta K. Pal, Hanzhe Zheng, Darren Tayama, Joaquim Bellmunt; John Hopkins University Sidney Kimmel Cancer Center, Baltimore, MD; City of Hope, Duarte, CA; Genentech, Inc., San Francisco, CA; Genentech, South San Francisco, CA; Dana-Farber Cancer Institute, Boston, MA
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
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. Barata PC, Gopalakrishnan D, Elson P, et al. Real-world experience with atezolizumab (atezo) in advanced urothelial cancer (UC). ASCO 2017, abstr e16031.