Up to half of mUC pts are ineligible for cis due to ECOG PS or comorbidities. These pts have been underserved in clinical trials and have a high unmet need. Carboplatin-based regimens are associated with notable toxicity, transient responses and mOS of 6-9 mo. Atezo is effective and tolerable in platinum-treated mUC and was tested in cis-ineligible pts as 1L treatment (tx).
Cis ineligibility criteria included any of: renal impairment (CrCl 30-60 ml/min), hearing loss or peripheral neuropathy ≥ G2 or ECOG PS2 (Table). Pts with no prior tx for mUC (> 12 mo since any perioperative tx) received 1200 mg atezo IV q3w until RECIST v1.1 PD. Primary endpoint was ORR (central review). PD-L1 on immune cells (IC) was centrally scored as IC2/3, 1 or 0 (SP142 IHC assay).
Of 119 evaluable pts, most (70%) had renal impairment. Confirmed ORR was 24%; CR rate was 7%. Responses were durable (21/28 ongoing at the 14 Mar 2016 data cut off), with mDOR not reached at 14.4 mo median follow up (mDOR range 3.7-16.6+). Responses occurred across all IC subgroups, in pts with poor prognostic factors and were enriched in upper tract primary disease (Table). mOS was 14.8 mo in all-comer pts (95% CI 10.1, NE; 47% event:pt ratio). With a median of 15 wk on tx, atezo was well tolerated (6% AE tx withdrawal) with no decline in renal function and a low immune-mediated AE rate. Common (≥ 10%) tx-related AEs were fatigue, pruritus and diarrhea. 1 tx-related G5 AE, sepsis, was seen. Updated OS and efficacy by molecular subtype, mutation load and microsatellite status will be presented.
IMvigor210a Cohort 1: ORR by Baseline Subgroups (All Pts)b
|n||ORR||95% CI||CR Rate|
|Primary tumor site|
|Renal pelvis||20||35%||15, 59||15%|
|Lymph node only||31||32%||17, 51||16%|
|Prior systemic therapy||22||36%||17, 59||9%|
|Bajorin risk factorsc|
|Cisplatin ineligibility criteriad|
|Renal impairment (GFR > 30 but 1 and/or visceral metastases. d Galsky, et al. J Clin Oncol. 2011.
1L atezo provided clinical benefit in cis-ineligible mUC, with a well-tolerated AE profile. Responses were persistent and continue to evolve with additional PRs/CRs observed with more follow up. These encouraging DOR and OS (vs historic and real world data) support atezo as a favorable alternative to chemo in the broader 1L mUC pt population.
Clinical trial identification
Legal entity responsible for the study
F. Hoffmann-La Roche Ltd.
J. Bellmunt: Advisory board with Genentech,inc. A. Balar: Consulting/advisory role: Roche, Cerulean, Pfizer, Dendreon. Research funding: Roche, Merck M.D. Galsky: Advisory Board: Genentech, Merck, Astellas, Novartis, Consulting: BioMotiv. Research funding: Novartis, NMS, Celgene. Y. Loriot: personal fees from Roche, grants and personal fees from Sanofi, personal fees from Astellas, personal fees from Jannsen, personal fees from Ipsen, personal fees from BMS, from null, outside the submitted work. C. Theodore: Travel and accomodations from Novartis and Sanofi. S. Bracarda: Advisory Board Member for: Bayer, Pfizer, Astellas, BMS, Novartis, Exelixis, Roche. Honoraria: Pfizer, Novartis, Astellas, Bayer, BMS. A. Necchi: personal fees from Roche, grants and personal fees from Merck Sharp & Dohme, from null, during the conduct of the study. S. Sridhar: Honoraria:Astellas Pharma, Janssen Oncology. Consulting/advisory: AstellaPharma, Janssen Pharmaceuticals, Sanofi, Bayer, Roche/Genentech, Bristol-Meyers Squibb Research funding: Sanofi M. van der Heijden: Roche/Genentech, Astellas, Astra Zeneca. B. Danner, S. Mariathasan, F. Legrand: Employee of Genentech, Inc. J.E. Rosenberg: non-financial support and other from Roche-Genetech; personal fees from Agensys, Eli Lilly, Merck, Sanofi, Oncogenex. All other authors have declared no conflicts of interest.