89PD - Results from OAK subgroup analyses: A randomized Phase III study of atezolizumab vs docetaxel in patients (pts) with advanced NSCLC

Date 07 May 2017
Event ELCC 2017
Session Targeted therapies and immunotherapies
Topics Non-Small-Cell Lung Cancer, Locally Advanced
Cancer Immunology and Immunotherapy
Lung and other Thoracic Tumours
Presenter Diego Cortinovis
Citation Annals of Oncology (2017) 28 (suppl_2): ii28-ii51. 10.1093/annonc/mdx091
Authors D. Cortinovis1, S.M. Gadgeel2, A. Rittmeyer3, F. Barlesi4, M. Cobo Dols5, T. Hida6, P. He7, M. Ballinger7, D.R. Gandara8, J. von Pawel9
  • 1Medical Oncology Unit, AOU San Gerardo, 20052 - Monza/IT
  • 2Karmanos Cancer Institute/Wayne State University, Detroit, Detroit/US
  • 3Lungenfachklinik Immenhausen, Immenhausen/DE
  • 4Aix Marseille University; Assistance Publique Hôpitaux de Marseille, Marseille/FR
  • 5Medical Oncology Section, Hospital Regional Universitario Carlos Haya, Malaga/ES
  • 6Aichi Cancer Center Hospital, Nagoya/JP
  • 7Genentech, Inc., South San Francisco/US
  • 8UC Davis Comprehensive Cancer Center, Sacramento/US
  • 9Asklepios-Fachkliniken München-Gauting, Gauting/DE

Abstract

Background

Atezolizumab (atezo) prevents binding of PD-L1 to its receptors PD-1 and B7.1, restoring tumor-specific T-cell immunity. Primary analysis of the Phase III OAK study in previously treated NSCLC showed superior survival with atezo vs docetaxel (doc) in the ITT population (mOS, 13.8 vs 9.6 months; HR, 0.73) and in pts expressing ≥1% PD-L1 on TC or IC (TC1/2/3 or IC1/2/3; mOS, 15.7 vs 10.3; HR, 0.74). Here we present further subgroup analyses.

Methods

OAK evaluated atezo vs doc in PD-L1 unselected NSCLC pts who had failed prior platinum-containing chemotherapy. Pts were stratified by PD-L1 expression, prior chemotherapy regimens and histology and randomized 1:1 to atezo (1200 mg) or doc (75 mg/m2) IV q3w. PD-L1 expression by IHC and mRNA was centrally evaluated by VENTANA SP142 IHC assay and Fluidigm, respectively. Data cutoff, July 7, 2016.

Results

In the first 850 of 1225 randomized pts (primary study population), OS was improved with atezo vs doc regardless of histology, and this benefit was seen across PD-L1 subgroups within each histology (Table). Similar OS was seen regardless of PD-L1 expression as assessed by mRNA and IHC. ORR was 14.4% vs 15.2% in non-squamous (non-sq) pts and 11.6% vs 8.2% (atezo vs doc) in squamous (sq) pts. Improved OS was seen with atezo vs doc across subgroups, including pts with treated baseline brain metastases (n = 85; mOS, 20.1 vs 11.9 mo; HR, 0.54; 95% CI, 0.63, 0.89) and never smokers (n = 156; mOS, 16.3 vs 12.6 mo; HR, 0.71; 95% CI, 0.47, 1.08). Further secondary endpoints and exploratory biomarker analyses for these subgroups and by age and EGFR/KRAS status will be presented.

Conclusions

OAK demonstrated clinically relevant improvements with atezo in the ITT population, including in both histology subgroups, regardless of PD-L1 expression (measured by IHC or tumor gene expression), and among other subgroups, including never smokers and pts with baseline brain metastases.rnTable: 89PDrn

rnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrn rnrn
rnOS
AtezoDocHRa 95% CI
nMedian, monMedian, mo
Non-sq population
TC3 or IC34922.5478.70.35 (0.21, 0.61)
TC2/3 or IC2/38918.79911.30.61 (0.42, 0.88)
TC1/2/3 or IC1/2/317117.616211.30.72 (0.55, 0.95)
TC0 and IC014014.015011.20.75 (0.57, 1.00)
All non-sq31315.631511.20.73 (0.60, 0.89)
Sq population
TC3 or IC32317.51811.60.57 (0.27, 1.20)
TC2/3 or IC2/34010.4379.70.76 (0.45, 1.29)
TC1/2/3 or IC1/2/3709.9608.70.71 (0.48, 1.06)
TC0 and IC0407.6497.10.82 (0.51, 1.32)
All sq1128.91107.70.73 (0.54, 0.98)
rna

Unstratified HRs.

rn

TC, tumor cell; IC, tumor-infiltrating immune cell.

rn

Clinical trial identification

NCT02008227

Legal entity responsible for the study

F. Hoffmann-La Roche Ltd/Genentech Inc., a member of the Roche Group

Funding

F. Hoffmann-La Roche Ltd/Genentech Inc., a member of the Roche Group

Disclosure

S.M. Gadgeel: Speaker\'s bureau from Astra-Zeneca, Genentech/Roche and Advisory Boards from Astra-Zeneca, Ariad, Pfizer, Bristol Myers- Squibb and Genentech/Roche. A. Rittmeyer: Grants as an advisor or speaker by Astra Zeneca, BMS, Boehringer Ingelheim, Eli Lilly, Pfizer and Roche Genentech. F. Barlesi: Honarium from Roche. T. Hida: Corporate-sponsored research from Chugai Pharmaceutical. P. He: Employee of Roche/Genentech, and has stocks for Roche and Amgen. Her husband has stocks for Allergan and Gilead. M. Ballinger: Genentech/Roche employee and has Roche stock. D.R. Gandara: Consultant for Genentech and clinical trial grant from Genentech. J. von Pawel: Adboard with fees paid to the institution from AbbVie, Pfizer, Bristol Myers Squibb, and Novartis. All other authors have declared no conflicts of interest.