LBA78 - IMpower110: Interim overall survival (OS) analysis of a phase III study of atezolizumab (atezo) vs platinum-based chemotherapy (chemo) as first-lin...

Date 27 September 2019
Event ESMO 2019 Congress
Session Proffered Paper 1 - NSCLC, metastatic
Topics Non-Small Cell Lung Cancer
Presenter David Spigel
Citation Annals of Oncology (2019) 30 (suppl_5): v851-v934. 10.1093/annonc/mdz394
Authors D. Spigel1, F. de Marinis2, G. Giaccone3, N. Reinmuth4, A. Vergnenegre5, C.H. Barrios6, M. Morise7, E. Felip8, Z.G. Andric9, S. Geater10, M. Özgüroğlu11, S. Mocci12, M. McCleland12, I. Enquist12, K.M. Komatsubara12, Y. Deng12, H. Kuriki12, X. Wen12, J. Jassem13, R.S. Herbst14
  • 1Tennessee Oncology, Sarah Cannon Research Institute, 37203 - Tennessee/US
  • 2Division Of Thoracic Oncology, European Institute of Oncology, 20141 - Milan/IT
  • 3Oncology, Lombardi Cancer Center Georgetown University, 20007 - Washington DC/US
  • 4Thoracic Oncology Department, Asklepios Lung Clinic, 82131 - Munich-Gauting/DE
  • 5Uotc Department- Unité Oncologie Thoracique Et Cutanée, CHU Limoges - Hopital Dupuytren, 87042 - Limoges/FR
  • 6School Of Medicine, PUCRS-Pontifícia Universidade do Rio Grande do Sul, 90619-900 - Porto Alegre/BR
  • 7Department Of Respiratory Medicine, Nagoya University, Graduate School of Medicine, 466-8550 - Nagoya/JP
  • 8Medical Oncology Service (lung Cancer Unit), Vall d'Hebron University Hospital, 08035 - Barcelona/ES
  • 9Medical Oncology Dep., Clinical Hospital Center Bezanijska Kosa, 11080 - Belgrade/RS
  • 10Intermal Medicine, Faculty Of Medicine, Prince of Songkla University, 90110 - Hat Yai, Songkhla/TH
  • 11Department Of Internal Medicine, Istanbul University - School of Medicine, Istandul/TR
  • 12Global Product Development Medical Affairs, Genentech, Inc., South San Francisco/US
  • 13Clinical Oncology And Radiotherapy, Medical University of Gdansk, 80-211 - Gdansk/PL
  • 14Medical Oncology, Yale University School of Medicine, 06520 - New Haven/US

Abstract

Background

PD-L1/PD-1 inhibitors (CPI) as monotherapy or combined with platinum-based doublet chemo (± bevacizumab) are 1L tx options in metastatic NSCLC, with choice of agent(s) determined by PD-L1 expression. For patients (pts) who may be ineligible for combination therapy, CPI monotherapy remains an attractive tx choice. IMpower110 evaluated atezo as 1L tx in PD-L1–selected pts independent of tumour histology.

Methods

IMpower110 enrolled 572 chemo-naive pts with stage IV nonsquamous (nsq) or squamous (sq) NSCLC, PD-L1 expression ≥ 1% on TC or IC, measurable disease by RECIST 1.1 and ECOG PS 0-1. Pts were randomised 1:1 to receive atezo 1200 mg IV q3w (Arm A) or platinum-based chemo (Arm B; 4 or 6 21-day cycles). Arm B nsq pts received cisplatin (cis) 75 mg/m2 or carboplatin (carbo) AUC 6 + pemetrexed 500 mg/m2 IV q3w; Arm B sq pts received cis 75 mg/m2 + gemcitabine (gem) 1250 mg/m2 or carbo AUC 5 + gem 1000 mg/m2 IV q3w. Stratification factors were sex, ECOG PS, histology and tumour PD-L1 status. The primary endpoint of OS is tested hierarchically in wild-type (WT; EGFR/ALK-negative) pts (TC3 or IC3 then TC2/3 or IC2/3 then TC1/2/3 or IC1/2/3).

Results

The 3 primary efficacy populations included 554 TC1/2/3 or IC1/2/3 WT pts, 328 TC2/3 or IC2/3 WT pts and 205 TC3 or IC3 WT pts. In the TC3 or IC3 WT population, atezo monotherapy improved median OS by 7.1 mo (HR, 0.595; P = 0.0106) vs chemo (Table); median follow-up was 15.7 mo. The safety population comprised 286 pts in Arm A and 263 pts in Arm B. Treatment-related AEs (TRAEs) and Grade 3-4 TRAEs occurred in 60.5% (Arm A) and 85.2% (Arm B), and 12.9% (Arm A) and 44.1% (Arm B), respectively.Table:

LBA78

Median OS
Arm A (atezo)Arm B (chemo)HRa 95% CIP valuea
nMonthsnMonths
TC3 or IC3 WT10720.29813.10.595 (0.398, 0.890)0.0106
TC2/3 or IC2/3 WT16618.216214.90.717 (0.520, 0.989)0.0416
TC1/2/3 or IC1/2/3 WT27717.527714.10.832 (0.649, 1.067)0.1481b

IC, tumour-infiltrating immune cells; TC, tumour cells. PD-L1 expression was centrally evaluated with the VENTANA SP142 IHC assay. TC3 or IC3 = TC ≥ 50% or IC ≥ 10% PD-L1+; TC2/3 or IC2/3 = TC ≥ 5% or IC ≥ 5% PD-L1+; TC1/2/3 or IC1/2/3 = TC ≥ 1% or IC ≥ 1% PD-L1+.

a

Stratified.

b

Only for descriptive purposes.

Conclusions

At this interim analysis, IMpower110 met the primary OS endpoint with statistically significant and clinically meaningful improvement in the TC3 or IC3 WT population. The safety profile favoured Arm A, with no new or unexpected safety signals seen.

Clinical trial identification

NCT02409342.

Editorial acknowledgement

Medical writing assistance was provided by Kia C. E. Walcott, PhD, of Health Interactions and funded by F. Hoffmann-La Roche, Ltd.

Legal entity responsible for the study

F. Hoffmann-La Roche.

Funding

F. Hoffmann-La Roche.

Disclosure

D. Spigel: Research grant / Funding (self): F. Hoffmann-La Roche . F. de Marinis: Research grant / Funding (institution): F. Hoffmann-La Roche. G. Giaccone: Research grant / Funding (institution): F. Hoffmann-La Roche. N. Reinmuth: Research grant / Funding (institution): F. Hoffmann-La Roche; Honoraria (self): BMS, Boehringer, AstraZeneca, MSD, Takeda, Pfizer, Merk. A. Vergnenegre: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: F. Hoffmann-La Roche, BMS, MSD, AstraZeneca. C.H. Barrios: Research grant / Funding (institution): Bristol Myers Squibb; Advisory / Consultancy, Research grant / Funding (institution): Pfizer, Novartis, Amgen, AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Roche/Genentech, Lilly, Sanofi, Taiho Pharmaceutical, Mylan, Merrimack, Merck, Abbvie, Astellas Pharma, Biomarin, Bristol-Myers Squibb, Daiichi Sankyo, Abraxis BioScience, AB Sc. M. Morise: Research grant / Funding (institution): F. Hoffmann-La Roche; Honoraria (self), Speaker Bureau / Expert testimony: Eli Lilly, Chugai, AstraZeneca, Ono, Pfizer, MSD, ; Research grant / Funding (institution): Chugai, AstraZeneca, Pfizer, Merk Serono, Kissei, Taiho, Novartis; Research grant / Funding (institution): Boehringer Ingelheim. E. Felip: Advisory / Consultancy, Speaker Bureau / Expert testimony: ABBVIE; Advisory / Consultancy, Speaker Bureau / Expert testimony: Astra Zeneca; Advisory / Consultancy: BergenBio; Advisory / Consultancy: Blue Print Medicines; Advisory / Consultancy, Speaker Bureau / Expert testimony: Boehringer Ingelheim; Advisory / Consultancy, Speaker Bureau / Expert testimony: Bristol-Meyers Squibb; Advisory / Consultancy: Celgene; Advisory / Consultancy, Speaker Bureau / Expert testimony: Eli Lilly; Advisory / Consultancy: Guardant Health; Advisory / Consultancy: Janssen; Advisory / Consultancy, Speaker Bureau / Expert testimony: Medscape; Advisory / Consultancy, Speaker Bureau / Expert testimony: Merck KGaA; Advisory / Consultancy, Speaker Bureau / Expert testimony: Merck Sharp & Dohme; Advisory / Consultancy, Speaker Bureau / Expert testimony: Novartis; Advisory / Consultancy, Speaker Bureau / Expert testimony: Pfizer; Advisory / Consultancy: Prime Oncology; Advisory / Consultancy, Speaker Bureau / Expert testimony: Roche; Advisory / Consultancy: Samsung; Advisory / Consultancy, Speaker Bureau / Expert testimony: Takeda; Advisory / Consultancy: Touchtime. Z.G. Andric: Research grant / Funding (institution): F. Hoffmann-La Roche. S. Geater: Research grant / Funding (institution): F. Hoffmann-La Roche. M. Özgüroğlu: Research grant / Funding (institution): F. Hoffmann-La Roche. S. Mocci: Full / Part-time employment: Roche/GNE. M. McCleland: Full / Part-time employment: Roche/GNE. I. Enquist: Full / Part-time employment: Roche/GNE. K.M. Komatsubara: Full / Part-time employment: Roche/GNE. Y. Deng: Full / Part-time employment: Roche/GNE. H. Kuriki: Research grant / Funding (institution): Roche/GNE; Shareholder / Stockholder / Stock options, Full / Part-time employment: Chugai Pharmaceutical. X. Wen: Full / Part-time employment: Roche/GNE. J. Jassem: Speaker Bureau / Expert testimony, Research grant / Funding (institution): F. Hoffmann-La Roche ; Advisory / Consultancy, Speaker Bureau / Expert testimony: Pfizer; Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca; Advisory / Consultancy: BMS; Advisory / Consultancy: MSD; Advisory / Consultancy: Takeda. R.S. Herbst: Honoraria (self): Roche/Genentech; Honoraria (self): Pfizer; Honoraria (self), Research grant / Funding (institution): AstraZeneca; Honoraria (self), Research grant / Funding (institution): Merck; Honoraria (self), Research grant / Funding (institution): Eli Lilly and Company; Honoraria (self): Abbvie Pharmaceuticals; Honoraria (self): ARMO Biosciences; Honoraria (self): Biodesix; Honoraria (self): Bristol-Myers Squibb; Honoraria (self): EMD Serrano; Honoraria (self): Genmab; Honoraria (self): Halozyme; Honoraria (self): Heat Biologics; Honoraria (self): Infinity Pharmaceuticals; Honoraria (self): Loxo Oncology; Honoraria (self): Merck and Company ; Honoraria (self): Nektar; Honoraria (self): Neon Therapeutics; Honoraria (self): NextCure; Officer / Board of Directors, non-executive/independent: Junshi Pharmaceticals; Honoraria (self): Sanofi; Honoraria (self): Seattle Genetics; Honoraria (self): Shire PLC; Honoraria (self): Spectrum Pharmaceuticals; Honoraria (self): Symphogen; Honoraria (self): Tesaro; Honoraria (self): Tocagen.