Pneumologie 2017; 71(S 01): S1-S125
DOI: 10.1055/s-0037-1598330
Posterbegehung – Sektion Pneumologische Onkologie
Lungenkarzinom I – Florian Fuchs/Erlangen, Christoph Schäper/Greifswald
Georg Thieme Verlag KG Stuttgart · New York

Updated survival and biomarker analyses of a randomized phase II study of atezolizumab vs. docetaxel in 2L/3L NSCLC (POPLAR)

A Rittmeyer
1   Lungenfachklinik Immenhausen
,
D Smith
2   US Oncology Research, Compass Oncology, Vancouver
,
J Vansteenkiste
3   University Hospitals Ku Leuven
,
L Fehrenbacher
4   Kaiser Permanente Medical Center
,
K Park
5   Division of Hematology/Oncology, Samsung Medical Centre
,
J Mazieres
6   Toulouse University Hospital
,
A Artal-Cortes
7   Servicio de Oncologia Medica, Hospital Universitario Miguel Servet
,
C Lewanski
8   Department of Oncology, Charing Cross Hospital
,
F Braiteh
9   US Oncology Research, Comprehensive Cancer Centers of Nevada, Las Vegas
,
J Yi
10   Genentech Inc.
,
P He
10   Genentech Inc.
,
W Zou
10   Genentech Inc.
,
D Waterkamp
10   Genentech Inc.
,
M Ballinger
10   Genentech Inc.
,
DS Chen
10   Genentech Inc.
,
A Sandler
10   Genentech Inc.
,
AI Spira
11   US Oncology Research, Virginia Cancer Specialists Research Institute, Fairfax
› Author Affiliations
Further Information

Publication History

Publication Date:
23 February 2017 (online)

 
 

    Background:

    Atezolizumab (atezo, MPDL3280A), a humanized engineered mAb, is the first anti-PD-L1 agent to show improved OS vs. docetaxel (doc) in NSCLC. These results correlate with PD-L1 expression on tumor cells (TC) and/or tumor-infiltrating immune cells (IC) and have shown improvement over time as reflected by the continued late separation of OS curves.

    Methods:

    Pts were randomized to receive atezo 1200 mg IV q3w or doc 75 mg/m2 IV q3w. Tumors were prospectively evaluated for PD-L1 expression using the SP142 IHC assay and scored from low to high (0 – 3). Gene expression was analyzed using a Fluidigm platform. The primary endpoint was OS and the primary analysis included 173 events among 287 randomized pts (event/patient ratio [EPR] 60%; min follow up 13 mo). Here we present data as of Dec 1, 2015 with a min follow up of 20 mo.

    Results:

    With longer follow up and 200 events (EPR 70%) further separation in survival curves and improvement in OS HR were seen for atezo over doc for ITT (HR 0.69, 95% CI 0.52 – 0.92) and across PD-L1 and histology subgroups (Table). Longer mDOR was seen for atezo vs. doc (18.6 vs. 7.2 mo). Improved OS with atezo over doc correlated with high tumor expression of Teff/IFNγ-associated genes (unstratified HR 0.52, 95% CI 0.32 – 0.83). Atezo continues to have a tolerable safety profile distinct from doc.

    OS

    Atezo

    Doc

    HR a

    PValue b

    n

    Median, mo

    n

    Median, mo

    95% CI

    ITT

    144

    12.6

    143

    9.7

    0.69

    0.52 – 0.92

    .011

    TC3 or IC3

    24

    NRC

    23

    11.1

    0.45

    0.22 – 0.95

    .033

    TC2/3 or IC2/3

    50

    15.1

    55

    7.4

    0.50

    0.31 – 0.80

    .003

    TC1/2/3 or

    IC1/2/3

    93

    15.1

    102

    9.2

    0.59

    0.41 – 0.83

    .003

    TC0 and IC0

    51

    9.7

    41

    9.7

    0.88

    0.55 – 1.42

    .601

    Squamous

    49

    10.1

    48

    8.6

    0.66

    0.41 – 1.05

    .075

    Nonsquamous

    95

    14.8

    95

    10.9

    0.69

    0.49 – 0.98

    .039

    aStratified for ITT, unstratified for subgroups

    bDescriptive only

    cNot reached

    Conclusions:

    Extended follow up reveals further separation late in OS curves and increased benefit with atezo monotherapy vs. doc. Relative to the primary analysis, OS benefit is improved in ITT and PD-L1 subgroups, including TC0 and IC0, and in pts with squamous NSCLC. In addition, PD-L1 expression measured by IHC and the tumor Teff/IFNγ gene signature, which reflects pre-existing immunity, can identify pts most likely to benefit from atezo.


    #

    No conflict of interest has been declared by the author(s).