LBA78 - IMpower110: Interim overall survival (OS) analysis of a phase III study of atezolizumab (atezo) vs platinum-based chemotherapy (chemo) as first-line (1L) treatment (tx) in PD-L1–selected NSCLC

• Published in: Annals of oncology Vol. 30; p. v915
• Main Authors: Spigel, D., de Marinis, F., Giaccone, G., Reinmuth, N., Vergnenegre, A., Barrios, C.H., Morise, M., Felip, E., Andric, Z.G., Geater, S., Özgüroğlu, M., Mocci, S., McCleland, M., Enquist, I., Komatsubara, K.M., Deng, Y., Kuriki, H., Wen, X., Jassem, J., Herbst, R.S.
• Format: Journal Article
• Language: English
• Published: Elsevier Ltd 01-10-2019
• ISSN: 0923-7534; 1569-8041
• DOI: 10.1093/annonc/mdz293

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.
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 1200mg IV q3w (Arm A) or platinum-based chemo (Arm B; 4 or 6 21-day cycles). Arm B nsq pts received cisplatin (cis) 75mg/m2 or carboplatin (carbo) AUC 6 + pemetrexed 500mg/m2 IV q3w; Arm B sq pts received cis 75mg/m2 + gemcitabine (gem) 1250mg/m2 or carbo AUC 5 + gem 1000mg/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).
The 3 primary efficacy populations included 554 TC1/2/3 or IC1/2/3WT pts, 328 TC2/3 or IC2/3WT pts and 205 TC3 or IC3WT pts. In the TC3 or IC3WT population, atezo monotherapy improved median OS by 7.1mo (HR, 0.595; P=0.0106) vs chemo (Table); median follow-up was 15.7mo. 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.TableLBA78TableMedian OSArm A (atezo)Arm B (chemo)HRa 95% CIP valueanMonthsnMonthsTC3 or IC3WT10720.29813.10.595 (0.398, 0.890)0.0106TC2/3 or IC2/3WT16618.216214.90.717 (0.520, 0.989)0.0416TC1/2/3 or IC1/2/3WT27717.527714.10.832 (0.649, 1.067)0.1481bIC, 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+.aStratified.bOnly for descriptive purposes.
At this interim analysis, IMpower110 met the primary OS endpoint with statistically significant and clinically meaningful improvement in the TC3 or IC3WT population. The safety profile favoured Arm A, with no new or unexpected safety signals seen.
NCT02409342.
Medical writing assistance was provided by Kia C. E. Walcott, PhD, of Health Interactions and funded by F. Hoffmann-La Roche, Ltd.
F. Hoffmann-La Roche.
F. Hoffmann-La Roche.
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.