Plat-refractory mUC pts have no therapies that significantly extend OS, which is
Pts who had progressed during/following plat received 1200 mg atezo IV q3w and could continue treatment past RECIST v1.1 PD until loss of clinical benefit. Co-primary endpoints were confirmed RECIST v1.1 ORR (central review) and immune-modified RECIST ORR (per investigator). PD-L1 status on immune cells (IC) was scored centrally (SP142 IHC assay): IC2/3, 1, 0.
310 pts (median 66 y) were evaluable: 78% had visceral mets; 43% had ≥ 2 prior mUC regimens. RECIST v1.1 ORR was 28% in IC2/3 pts (95% CI: 19, 38), 19% (14, 25) in IC1/2/3 and 16% (12, 20) in all pts. Both CRs (15% in IC2/3; 9% in IC1/2/3; 7% in all pts) and PRs occurred in pts with poor prognostic factors and were durable (71% ongoing at the 14 Mar 2016 data cut off). mDOR was not reached with a 17.5-mo mFU (range, 0.2 + -21.1). Among 134 pts continuing treatment post PD, 19% had subsequent ≥ 30% decrease in target lesions. 1-y OS was 50% in IC2/3 pts (95% CI: 40, 60), 40% (33, 47) in IC1/2/3 and 37% (31, 42) overall, with 30% of all pts alive. Overall and subgroup mOS are in the Table. Atezo remained well tolerated with low rates of immune-mediated AEs and discontinuations. 70% of pts had a related AE (mostly fatigue [31%]; nausea [14%]), 16% were G3-4 (no G5 events). > 1-y safety, biomarker correlates of OS (immune gene expression, mutation load) and TCGA classification will be presented.
Median OS in IMvigor210a Cohort 2 Subgroups
|Subgroup||n||mo||95% CI||n||mo||95% CI||n||mo||95% CI|
|All||100||11.9||9.0, 17.9||207||9.0||7.1, 10.9||310||7.9||6.7, 9.3|
|Prior regimens for mUC|
|0||24||8.5||3.9, NE||42||9.5||5.7, 12.8||58||9.5||5.9, 15.5|
|1||34||NE||10.9, NE||79||10.9||8.0, 13.3||120||9.0||7.2, 11.3|
|2||20||17.0||2.8, NE||43||6.2||3.1, 17.8||66||5.9||3.3, 8.7|
|3||12||8.7||5.0, 16.5||26||6.6||4.5, 10.2||42||6.4||3.8, 10.2|
|≥4||10||13.8||2.7, NE||17||8.0||2.5, 17.9||24||7.4||4.6, 11.1|
|Bellmunt risk factors:b|
|0||31||NE||17.1, NE||61||NE||17.8, NE||83||NE||17.1, NE|
|1||35||11.9||5.1, NE||72||8.3||5.1, 13.3||117||6.8||5.4, 10.3|
|2||28||9.0||2.5, 11.4||59||5.1||2.9, 8.0||89||5.0||3.1, 6.5|
|3||6||5.3||2.8, 7.2||15||3.4||2.8, 5.7||21||3.4||2.1, 5.0|
|Primary tumor site|
|Upper tract||18||10.9||7.4, NE||42||8.3||5.1, 11.4||69||7.6||5.0, 10.5|
|Bladder||79||12.8||7.2, NE||160||9.0||6.7, 11.4||233||7.9||6.4, 9.6|
|Lymph node only||24||17.7||9.3, NE||39||17.8||9.3, NE||43||17.8||9.3, NE|
|Visceral||66||9.9||6.2, 16.5||152||7.3||5.8, 9.5||243||7.0||5.9, 8.1|
a Study ID NCT02108652. b Defined as baseline ECOG PS ≥ 1, liver metastasis, and/or hemoglobin
Heavily pre-treated mUC pts on atezo monotherapy had durable responses, with encouraging OS. Combined with favorable safety, atezo may transform treatment of plat-treated mUC. A randomized Ph III study vs chemo in this population is ongoing (NCT02302807).
Clinical trial identification
Legal entity responsible for the study
F. Hoffmann-La Roche Ltd
F. Hoffmann-La Roche Ltd
Y. Loriot: grants and personal fees from Sanofi, personal fees from Roche, Astellas, Jannsen, Ipsen. Personal fees from BMS, from null, outside the submitted work. J.E. Rosenberg: Non-financial support and other from Roche-Genetech, personal fees from Agensys, Eli Lilly, Merck, Sanofi, Oncogenex. T.B. Powles: Honoraria: Roche, BMS, Merck. Research Funding: Roche, AstraZeneca. A. Necchi: personal fees from Roche, grants and personal fees from Merck Sharp & Dohme. I. Duran: Cnsulting/advisory: Jansen, Roche, Amgen, Novartis, Pierre fabre. Travel, Accomdations: Astellas. C. Theodore: Travel and accommodation expenses from Novartis, Sanofi. J.L. Perez-Gracia: Grant from Roche. A. Thåström, B. Danner, S. Mariathasan, O. Abidoye: Employee and shareholder of Genentech, Inc. M. van der Heijden: Roche/Genentech - Reimbursement for patient care and data management of study subjects. advisory board: Roche/GenentechAstellas, Astra Zeneca. Astellas - Research grant. All other authors have declared no conflicts of interest.