852PD - Atezolizumab (atezo) in Platinum-Treated Locally Advanced or Metastatic Urothelial Carcinoma (mUC): Post-Progression Outcomes from the Phase 2 IMvi...

Date 10 September 2017
Event ESMO 2017 Congress
Session Genitourinary tumours, non-prostate
Topics Urothelial Cancers
Cancer Immunology and Immunotherapy
Genitourinary Cancers
Presenter Andrea Necchi
Citation Annals of Oncology (2017) 28 (suppl_5): v295-v329. 10.1093/annonc/mdx371
Authors A. Necchi1, R.W. Joseph2, Y. Loriot3, J. Hoffman-Censits4, J.L. Perez Gracia5, D.P. Petrylak6, Q. Zhu7, B. Ding7, C. Kaiser7, J.E. Rosenberg8
  • 1Medical Oncology, Fondazione IRCCS - Istituto Nazionale dei Tumori, 20133 - Milan/IT
  • 2Department Of Hematology/oncology, Mayo Clinic, 32224 - Jacksonville/US
  • 3Oncology, Institut Gustave Roussy, 94800 - Villejuif/FR
  • 4Thomas Jefferson University Hospital, Sidney Kimmel Cancer Center, Philadelphia/US
  • 5Medical Oncology, Clinica Universidad de Navarra, Pamplona/ES
  • 6Smilow Cancer Center, Yale University School of Medicine Medical Oncology, 06520-8032 - New Haven/US
  • 7Oncology, Genentech, Inc., South San Francisco/US
  • 8Oncology, Memorial Sloan-Kettering Cancer Center, 10065 - New York/US

Abstract

Background

mUC remains a disease with few treatment (tx) options and short OS. IMvigor210 demonstrated efficacy and safety of atezo (anti–PD-L1) in mUC and led to approval in the US and elsewhere. Here, we evaluate outcomes in platinum-treated IMvigor210 patients (pts) treated with atezo beyond progression.

Methods

IMvigor210 (NCT02108652 cohort 2) enrolled pts with mUC that progressed during/following platinum. Atezo was given 1200 mg IV q3w until loss of clinical benefit per investigator. In this descriptive, post hoc analysis (data cut 4 Jul 2016), assessments included on-study RECIST v1.1 response (pre– and post–first progressive disease [PD]; central review), sum of target lesion diameters (SLD; % change from PD), OS, post-progression (pp) OS and safety grouped by tx status post-PD.

Results

220 pts who experienced PD (of 310 total in study) were evaluable: 137 continued atezo post-PD, and 83 received other (n = 19) or no (n = 64) systemic tx. Pts who continued atezo had fewer poor prognostic factors (Table). Pre-PD tx duration was similar in pts who did or did not continue atezo post-PD (median, 1.5 and 1.4 mo, respectively), and median post-PD atezo duration was 1.6 mo. Pts continuing atezo beyond PD had higher pre-PD ORR vs other groups (Table). 45 pts who continued atezo following initial PD (of 108 with post–first PD measurements) experienced decreases in target lesion SLD. OS data are in Table. In pts continuing atezo, pre- and post-PD exposure-adjusted tx-related AEs were similar (Table), with no related G5 AEs.Table:

852PD Key baseline characteristics and outcomes in patients treated beyond first RECIST v1.1 PD

ATEZO TREATMENT BEYOND PD (n = 137)NO ATEZO BEYOND PD (n = 83)NO ATEZO BEYOND PD (n = 83)
Other systemic tx (n = 19)No systemic tx (n = 64)
Characteristic
Median age66 yr67 yr65 yr68 yr
Male sex80%71%63%73%
Primary site: bladder75%75%79%73%
ECOG PS 043%31%42%28%
Mets, visceral/liver82%/27%87%/41%84%/42%88%/41%
Response (with respect to study entry [baseline])
Pre-PD RECIST v1.1 ORR12%1%0%2%
Post-PD RECIST v1.1 ORR1%0%0%0%
Overall survival
Median follow-up duration (event/pt rate)21.2 mo (70%)20.0 mo (92%)19.0 mo (90%)20.0 mo (92%)
OS, median12.8 mo3.6 mo8.8 mo2.9 mo
18-mo OS33.4%3.9%10.5%1.7%
ppOS, median8.6 mo1.5 mo6.8 mo1.2 mo
12-mo ppOS37.1%2.7%10.5%0%
Treatment-related AEs, % (exposure-adjusted rate)
All Gr: on/before PD (total of 18 pt-yr)66% (512 per 100 pt-yr)
All Gr: after PD (total of 31 pt-yr)53% (234 per 100 pt-yr)
Gr 3-4: on/before PD (total of 43 pt-yr)9% (28 per 100 pt-yr)
Gr 3-4: after PD (total of 60 pt-yr)9% (22 per 100 pt-yr)

Conclusions

Pts who continued atezo beyond PD derived prolonged clinical benefit including tumor burden reduction and numerically longer OS vs pts who discontinued atezo post-PD in this single-arm study. Atezo was well tolerated throughout tx. An important future challenge in the post-PD setting will be to identify pts most likely to respond to atezo and appropriate sequencing of chemo agents thereafter.

Clinical trial identification

NCT02108652

Legal entity responsible for the study

F. Hoffman-La Roche Ltd.

Funding

F. Hoffman-La Roche Ltd.

Disclosure

A. Necchi: Reports personal fees from Roche, grants and personal fees from Merck Sharp & Dohme. R.W. Joseph: Reports personal fees from Bristol-Myers Squib, personal fees from Merck, personal fees from Nektar, personal fees from Eisai, personal fees from Novartis, personal fees from Cerulean, outside the submitted work. Y. Loriot: Consultancy: Sanofi, Astellas, Janssen, Roche AstraZeneca, MSD; Travel, accomodations, expenses: Astellas, Roche, MSD. J. Hoffman-Censits: Consultancy: Roche genentech, outside the submitted work. J.L. Perez Gracia: Reports grants from Roche, during the conduct of the study. D.P. Petrylak: Grants and personal fees from Genetech, during the conduct of the study; grants and personal fees from Merck, AstraZeneca, Novartis, Pfizer, Agenysis, outside the submitted work. Q. Zhu, B. Ding, C. Kaiser: Employee and stock owner - Genentech, Inc. J.E. Rosenberg: Reports non-financial support from Roche-Genetech, during the conduct of the study; personal fees from Agensys, Eli Lilly, Merck, Sanofi, Oncogenex, outside the submitted work.