Atezolizumab (atezo) in platinum (plat)-treated locally advanced/metastatic urothelial carcinoma (mUC): Updated OS, safety and biomarkers from the Ph II IMvigor210 study

Date

09 Oct 2016

Session

Poster display

Presenters

Yohann Loriot

Citation

Annals of Oncology (2016) 27 (6): 266-295. 10.1093/annonc/mdw373

Authors

Y. Loriot¹, J.E. Rosenberg², T.B. Powles³, A. Necchi⁴, S. Hussain⁵, R. Morales Barrera⁶, M. Retz⁷, G. Niegisch⁸, I. Duran⁹, C. Theodore¹⁰, J.L. Perez-Gracia¹¹, E. Grande Pulido¹², A. Thåström¹³, B. Danner¹³, S. Mariathasan¹³, O. Abidoye¹³, M. van der Heijden¹⁴

Author affiliations

¹ Oncology, Institut Gustave Roussy, 94805 - Villejuif/FR
² Medical Oncology, Memorial Sloan-Kettering Cancer Center, 10065 - New York, NY/US
³ Department Of Medical Oncology, Barts Cancer Institute-Queen Mary University of London, EC1M 6BQ - London/GB
⁴ Medical Oncology/urology Unit, Fondazione IRCCS - Istituto Nazionale dei Tumori, 20133 - Milano/IT
⁵ Molecular And Clinical Cancer Medicine, University of Liverpool-Royal Liverpool University Hospital,, L69 3GA - Liverpool/GB
⁶ Oncologia Médica, Vall d`Hebron University Hospital Institut d'Oncologia, 08035 - Barcelona/ES
⁷ Technische Universität München, Urologische Klinik und Poliklinik, München/DE
⁸ Heinrich Heine University Düsseldorf, Univesitätsklinikum Düsseldorf, Düsseldorf/DE
⁹ Departamento De Oncologia, Hospital Universitario Virgen del Rocio, 41013 - Sevilla/ES
¹⁰ Medical Oncology, Hopital Foch Service d'Oncologie, Suresnes/FR
¹¹ Medical Oncology, Universidad de Navarra, 31008 - Pamplona/ES
¹² Medical Oncology, Hospital Universitario Ramon y Cajal, 28031 - Madrid/ES
¹³ Oncology, Genentech, Inc., South San Francisco/US
¹⁴ Oncology, The Netherlands Cancer Institute, Amsterdam/NL

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 IMvigor210^a 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.

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