438O - Primary analysis from OAK, a randomized phase III study comparing atezolizumab with docetaxel in 2L/3L NSCLC

Date 18 December 2016
Event ESMO Asia 2016 Congress
Session Presidential Symposium
Topics Anticancer agents
Non-Small-Cell Lung Cancer, Metastatic
Immunotherapy
Presenter Keunchil Park
Citation Annals of Oncology (2016) 27 (suppl_9): ix139-ix156. 10.1093/annonc/mdw594
Authors F. Barlesi1, K. Park2, F. Ciardiello3, J. von Pawel4, S. Gadgeel5, T. Hida6, D. Kowalski7, M. Cobo Dols8, D. Cortinovis9, J. Leach10, J. Polikoff11, D.R. Gandara12, C. Barrios13, D.S. Chen14, P. He14, M. Kowanetz15, M. Ballinger16, D. Waterkamp16, A. Sandler16, A. Rittmeyer17
  • 1Assistance Publique Hôpitaux De Marseille, Aix Marseille University, 13915 - Marseille/FR
  • 2Div Of Hem/onc, Dept Of Med, Samsung Medical Center Sungkyunkwan University School of Medicine, 135-710 - Seoul/KR
  • 3N/a, Seconda Università degli Studi di Napoli, Napoli/IT
  • 4N/a, Asklepios-Fachkliniken Mönchen-Gauting, Gauting/DE
  • 5N/a, Karmanos Cancer Institute/Wayne State University, Detroit/US
  • 6Dept. Of Thoracic Oncology, Aichi Cancer Center Hospital, Nagoya/JP
  • 7Department Of Lung Cancer And Chest Tumours, Oncology Centre, Institute M. Sklodowska - Curie, Warsaw/PL
  • 8N/a, Medical Oncology Section, Hospital Regional Universitario Carlos Haya, Malaga/ES
  • 9N/a, Medical Oncology Unit, AOU San Gerardo, Monza/IT
  • 10N/a, Minnesota Oncology, Minneapolis/US
  • 11N/a, Southern California Permanente Medical Group, San Diego/US
  • 12Division Of Hematology And Oncology, UC Davis Comprehensive Cancer Center, Sacramento/US
  • 13Department Of Medicine, PUCRS School of Medicine, Porto Alegre/BR
  • 14N/a, Genentech, Inc., 94080 - South San Francisco/US
  • 15Oncology Biomarker Development, Genentech, Inc., 94080 - South San Francisco/US
  • 16Product Development Oncology, Genentech, Inc., South San Francisco/US
  • 17N/a, Lungenfachklinik Immenhausen, Immenhausen/DE

Abstract

Background

Atezolizumab (atezo) inhibits the binding of PD-L1 to its receptors PD-1 and B7.1, thereby restoring tumor-specific T-cell immunity, while leaving the PD-L2/PD-1 interaction intact. Atezo demonstrated survival benefit vs docetaxel (doc) in the Ph2 trial POPLAR. Here we present the primary analysis from the Ph3 OAK study evaluating atezo vs doc in previously treated NSCLC.

Methods

Previously treated NSCLC patients (pts) were stratified by PD-L1 status, prior chemotherapy regimens (1 vs 2) and histology, and randomized 1:1 to atezo (1200 mg IV q3w) or doc (75 mg/m2 IV q3w). The co-primary endpoints were OS in the ITT and PD-L1–expression subgroup TC1/2/3 or IC1/2/3 (PD-L1 expression on ≥ 1% TC or IC). Secondary endpoints included PFS, ORR, DoR and safety.

Results

The primary efficacy analysis was conducted in the first 850 of 1225 total enrolled pts. Pts had a median age of 64 y, 61% were male, 25% had 2 prior lines of therapies, 26% had squamous histology, 67% were previous smokers and 37% were PS 0. Superior OS was seen with atezo vs doc in ITT (HR 0.73; P = .0003) and TC1/2/3 or IC1/2/3 pts (HR 0.74; P = .0102). Survival was improved regardless of PD-L1 expression levels, including in pts with no PD-L1 expression (TC0 and IC0). There was pronounced benefit in pts with high PD-L1 expression (TC3 or IC3). OS benefit was similar in pts with squamous or nonsquamous histology. In ITT pts, PFS HR was 0.95 (2.8 vs 4.0 mo), ORR 13.6% vs 13.4%, and DoR 16.3 vs 6.2 mo for atezo vs doc. Gr 3-4 treatment-related AEs occurred in 15% of atezo pts and 43% of doc pts. There were no deaths related to atezo and 1 related to doc. No new safety signal was observed.

Conclusions

This first Ph3 trial of a PD-L1-directed drug in NSCLC demonstrates that atezo treatment results in a statistically significant and clinically relevant improvement in OS vs doc in 2L/3L NSCLC, regardless of PD-L1 expression and histology. Atezo was well tolerated with a favorable safety profile vs doc.rn

Table: 438O

rnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrn
rnOS
rnAtezoDocHRa (95% CI)P Value
nMedian, monMedian, mo
ITT42513.84259.60.73 (0.62, 0.87)0.0003b
TC1/2/3 or IC1/2/324115.722210.30.74 (0.58, 0.93)0.0102b
TC2/3 or IC2/312916.313610.80.67 (0.49, 0.90)0.0080
TC3 or IC37220.5658.90.41 (0.27, 0.64)

Clinical trial indentification

NCT02008227

Legal entity responsible for the study

F. Hoffmann-La Roche Ltd

Funding

F. Hoffmann-La Roche Ltd

Disclosure

K. Park: Consulting Astellas, Astra-Zeneca, AVEO, Boehringer Ingelheim, Clovis, Eli Lilly, Hanmi, KHK Novartis, Ono, Roche, grants and research funding from Astra-Zeneca. F. Ciardiello: Advisory boards: Merck Serono, Astrazeneca, Lilly, Roche, Bayer. J. von Pawel: Consultant/Advisory (compensated) role for Paischi, Pfizer, Vertex, Cloves. S. Gadgeel: Served on Advisory Boards and was compensated by the following pharmaceutical companies- Roche/Genentech, Pfizer, BMS, Ariad, Boehringer-Ingelheim, Astra-Zeneca. Speaker\'s Bureau- Astra-Zeneca. T. Hida: Corporate-sponsored research: Chugai Pharmaceutical. J. Leach: Advisory boards: Merck Serono, Astrazeneca, Lilly, Roche, Bayer. D.R. Gandara: Grant and consultant: Genentech, BMS, MERCK and EMD Serrano. C. Barrios: Boehringer-Ingelheim, GSK, Novartis, Pfizer, Roche/Genentech, Eisai, Bioepis. D.S. Chen: Genentech employee and stocks Roche. P. He: past employee of Amgen, current employee of Genentech. I do own stocks of Roche/Amgen, and my family members own stocks of Gilead and Allergan. M. Kowanetz: Employee of Genentech and Genentech stock. M. Ballinger: Genentech employee and Roche stocks. D. Waterkamp: Roche/Genentech employee and Roche stock. A. Sandler: Genentech employee. A. Rittmeyer: Consulting or advisory role for Roche, Lilly, BMS, Boehing. Grants: Roche, Lilly, BMS, AstraZeneca, MSD, Boehringer Ingelheim, Pfizer. All other authors have declared no conflicts of interest.