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.