Abstract 3424
Background
Plat-refractory mUC pts have no therapies that significantly extend OS, which is
Methods
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.
Results
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
| IC2/3 | IC1/2/3 | All | |||||||
|---|---|---|---|---|---|---|---|---|---|
| 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 |
| Metastatic site | |||||||||
| 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
Conclusions
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
ClinicalTrials.gov NCT02108652
Legal entity responsible for the study
F. Hoffmann-La Roche Ltd
Funding
F. Hoffmann-La Roche Ltd
Disclosure
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.