Background.
1L treatment options for mUC currently include platinum-based chemo and/or checkpoint inhibitors such as atezo (anti–PD-L1), depending on pt eligibility factors. IMvigor210 was a Phase 2 study of atezo in mUC; Cohort 1 investigated atezo as 1L treatment in cis-ineligible pts (Balar Lancet 2016, ASCO 2018). Here we evaluate Cohort 1 efficacy over time, including outcomes by PD-L1 status.
Methods.
Cohort 1 (NCT02951767) pts were treatment naive for mUC, had ECOG PS ≤2 and were considered cis ineligible by ≥1 of the following: GFR >30 and <60 mL/min, ≥G2 hearing loss or peripheral neuropathy or ECOG PS 2. Atezo 1200 mg IV q3w was given until RECIST v1.1 PD or intolerable toxicity. We evaluated RECIST v1.1 ORR by independent review (primary endpoint [EP]), DOR and OS (secondary EPs) in ITT pts and subgroups based on PD-L1 status on tumor-infiltrating immune cells (VENTANA SP142 assay; IC2/3, ≥5%; IC0/1, <5%) across 4 datacuts.
Results.
Efficacy data over time are in the Table (n=119 evaluable pts). Notably, between the initial 2015 and recent 2017 datacuts, ORR (95% CI) in PD-L1 IC2/3 pts increased from 22% (9, 40) to 28% (14, 47), with the CR rate increasing from 3% to 13%. Over the same period, IC0/1 ORR (95% CI) increased from 18% (11, 28) to 22% (14, 32), and the CR rate from 6% to 7%. Responses in many pts appeared durable regardless of PD-L1 status, with 68%, 67% and 68% of ITT, IC2/3 and IC0/1 responses ongoing as of July 12th, 2017, respectively; mDOR was not yet reached in ITT and IC2/3 pts (as of July 12th, 2017, IC0/1 mDOR was 30.4 mo). mOS also increased over time (Table). At the 2017 cutoff, the 2-y OS (NE in prior datacuts) was 41% in ITT pts, 39% in IC2/3 pts and 42% in IC0/1 pts.
Conclusions.
In IMvigor210 Cohort 1, evolution of ORR, CR, and OS was seen with additional follow-up, including late responses and conversions to CR, particularly in the IC2/3 subgroup. Atezo monotherapy provided notable durable clinical benefit as 1L treatment for cis-ineligible pts with mUC.
|
Sept 14, 2015
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Primary analysis:
Mar 14, 2016
|
July 4, 2016
|
July 12, 2017
|
Median follow-up, mo
|
8.5
|
14.4
|
17.2
|
29.3
|
|
ITT (N=119)
|
ORR, n (%)
|
23 (19)
|
28 (24)
|
27 (23)
|
28 (24)
|
CR rate, n (%)
|
6 (5)
|
8 (7)
|
11 (9)
|
10 (8)
|
mOS, mo
|
10.6
|
14.8
|
15.9
|
16.3
|
1-y OS, %
|
49
|
57
|
57
|
58
|
|
IC2/3 (n=32)
|
ORR, n (%)
|
7 (22)
|
9 (28)
|
9 (28)
|
9 (28)
|
CR rate, n (%)
|
1 (3)
|
2 (6)
|
4 (13)
|
4 (13)
|
mOS, mo
|
10.6
|
12.3
|
12.3
|
12.3
|
1-y OS, %
|
36
|
52
|
52
|
52
|
|
IC0/1 (n=87)
|
ORR, n (%)
|
16 (18)
|
19 (22)
|
18 (21)
|
19 (22)
|
CR rate, n (%)
|
5 (6)
|
6 (7)
|
7 (8)
|
6 (7)
|
mOS, mo
|
NE
|
15.3
|
19.1
|
19.1
|
1-y OS, %
|
52
|
59
|
59
|
60
|
COI/Disclosures:
I. Duran has participated on Advisory Boards for MSD, Bristol-Myers Squibb, Roche-Genentech and Sanofi and has received research funding and travel expenses from Astra-Zeneca and Roche-Genentech.
R. Dreicer has had a consultant/advisory role for Astellas Pharma, AstraZeneca, Bristol-Myers Squibb, EMD Serono, Genentech/Roche, Incyte and Pfizer; his institution has received research funding from Genentech, Lilly, Merck and Seattle Genetics.
Y. Loriot has had a consulting/advisory role with Astellas Medivation, AstraZeneca, Janssen, MSD, Roche, Sanofi and Seattle Genetics; he has received travel/accommodations/expenses from AstraZeneca, MSD, Roche, and Seattle Genetics. His institution has received research funding from Sanofi.
J.L.P. Gracia has had a consulting/advisory role, received research funding, received travel/accommodations/expenses and participated in Speakers’ Bureaus with Bristol-Myers Squibb and Roche; he has received research funding from MSD.
JH Hoffman-Censits has received honoraria from Clovis Oncology and Roche/Genentech and has had a consulting/advisory role with Foundation Medicine and Roche/Genentech; she has received research funding from Sanofi and travel/accommodations/expenses from Roche/Genentech.
D.P. Petrylak has ownership interest in Bellicum Pharmaceuticals and Tyme, Inc, has received honoraria from Astellas Pharma, Bayer, Bellicum Pharmaceuticals, Exelixis, Ferring, Genentech, Johnson & Johnson, Medivation, Merck Serono, Millennium, Pfizer, Progenics, and Sanofi, and has had consultancies with Bayer, Bellicum Pharmaceuticals, Dendreon, Exelixis, Ferring, Johnson & Johnson, Medivation, Millennium, Pfizer, and Sanofi.
M.S. van der Heijden has had a consulting/advisory role with Astellas Pharma, AstraZeneca/MedImmune, Bristol-Myers Squibb, and Roche/Genentech; he has received research funding from Astellas Pharma, and travel/accommodations/expenses from Astellas Pharma, MSD Oncology, and Novartis.
B. Ding is an employee of Genentech and a shareholder of Roche.
X. Shen is an employee of Genentech and shareholder of Roche.
V. Antic is an employee and shareholder of Roche.
J.E. Rosenberg has stock and other ownership interests in Illumina. He has received honoraria from AstraZeneca, Bristol-Myers Squibb, Medscape, Peerview, UpToDate, and Vindico; he has had a consulting or advisory role with Agensys, AstraZeneca/MedImmune, Bayer, Bristol-Myers Squibb, EMD Serono, Inovio Pharmaceuticals, Lilly, Merck, Roche/Genentech, Sanofi, and Seattle Genetics. He has received research funding from Agensys, Genentech/Roche, Incyte, Mirati Therapeutics, Novartis, Oncogenex, and Viralytics. He has received travel/accommodations/expenses from Bristol-Myers Squibb and Genentech/Roche.
A.V. Balar has received honoraria from Genentech/Roche and Merck; he has had a consulting or advisory role with AstraZeneca/MedImmune, Cerulean Pharma, Genentech/Roche, Merck, Pfizer/EMD Serono, Incyte and Kyowa Kirin; he has received research funding from AstraZeneca/MedImmune, Genentech/Roche, Merck, and Seattle Genetics.