1201O - Gefitinib/chemotherapy vs chemotherapy in EGFR mutation-positive NSCLC after progression on 1st line gefitinib (IMPRESS study): Final overall survi...

Date 09 October 2016
Event ESMO 2016 Congress
Session NSCLC, metastatic 1
Topics Non-Small-Cell Lung Cancer, Metastatic
Presenter Jean-Charles Soria
Citation Annals of Oncology (2016) 27 (6): 416-454. 10.1093/annonc/mdw383
Authors J. Soria1, S. Kim2, Y. Wu3, K. Nakagawa4, J. Yang3, M. Ahn5, J. Wang6, J.C. Yang7, Y. Lu8, S. Atagi9, S. Ponce Aix10, Y. Rukazenkov11, R. Taylor11, T.S.K. Mok12
  • 1Department Of Medicine, Institut de Cancérologie Gustave Roussy, 94800 - Villejuif/FR
  • 2Department Of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul/KR
  • 3Guandong Lung Cancer Institute, Guangdong General Hospital, Guangzhou/CN
  • 4Department Of Medical Oncology, Kindai University, Osaka/JP
  • 5Department Of Medicine, Samsung Medical Center Sungkyunkwan University School of Medicine, Seoul/KR
  • 6Department Of Thoracic Medical Oncology, Beijing Cancer Hospital and Institute, Beijing/CN
  • 7Department Of Oncology, National Taiwan University Hospital, Taipei/TW
  • 8Department Of Thoracic Cancer, West China Medical School, Sichuan University, Sichuan/CN
  • 9Department Of Thoracic Oncology, Kinki-chuo Chest Medical Center, Osaka/JP
  • 10Medical Oncology Service, University Hospital 12 De Octubre, Madrid/ES
  • 11Global Medicines Development, AstraZeneca, Macclesfield/GB
  • 12Department Of Clinical Oncology, Chinese University of Hong Kong Prince of Wales Hospital, Hong Kong/CN

Abstract

Background

IMPRESS (NCT01544179) evaluated continuation of gefitinib plus cisplatin/pemetrexed (cis/pem) (G) vs placebo plus cis/pem (P) in patients (pts) with acquired resistance to 1st line gefitinib. Primary results (progression-free survival [PFS]) confirmed that continuing gefitinib in addition to cis/pem is of no clinical benefit. We present final OS data.

Methods

Pts (age ≥18 years, chemo-naïve, locally advanced/metastatic NSCLC with activating EGFR mutation, progression on 1st line gefitinib) from 61 centres (Europe/Asia Pacific) were randomised to G or P (gefitinib 250 mg/day or placebo; plus cis 75 mg/m2/pem 500 mg/m2). Primary endpoint: PFS. Secondary endpoints included: OS and safety/tolerability. In pre-planned biomarker analyses, EGFR T790M mutation status was analysed via plasma circulating free tumour-derived DNA.

Results

A total of 265 pts were randomised (G 133; P 132) and followed until 175 (66%) had died (16 Nov 2015); most deaths (G 65%; P 55%) were related to disease progression. Continuation of gefitinib plus cis/pem was detrimental to OS vs P (hazard ratio [HR] 1.44, p = 0.016). Subgroup data by plasma T790M mutation status showed HR 1.49 for T790M-positive and HR 1.15 for T790M-negative (Table). More pts randomised to P vs G (both n = 132; 71% vs 61%) received post-discontinuation therapy, with differing EGFR TKI exposure (36% vs 23%). Gefitinib plus cis/pem continued to be well tolerated, with no new unexpected safety findings.

Conclusions

Final IMPRESS OS data indicate that pts with acquired resistance to 1st line gefitinib should not continue to receive the TKI plus doublet chemotherapy beyond progression, due to the observed detrimental effect on OS. Exploratory plasma biomarker analyses suggest that this effect may be driven by T790M-positive status; inconclusive data in the T790M-negative subgroup warrant further investigation.

OS n/N HR 95% CI Median OS (months), G vs P
Overall G 94/133; P 82/132 1.44 1.07, 1.94 13.4 vs 19.5
Overall with additional covariates
Presence/absence of brain metastases and T790M mutation status (positive/negative/unknown) at baseline G 94/133; P 82/132 1.31 0.97, 1.77 -
Subgroup (mutation status by baseline plasma sample)
T790M mutation-positive G 63/81; P 44/61 1.49 1.02, 2.21 10.8 vs 14.1
T790M mutation-negative G 27/46; P 30/59 1.15 0.68, 1.94 21.4 vs 22.5
T790M informativea G 11/19; P 20/31 0.93 0.42, 1.94 18.4 vs 19.5
T790M non-informativeb G 13/24; P 10/28 1.59 0.69, 3.77 25.8 vs NC

a 

Clinical trial identification

NCT01544179

Legal entity responsible for the study

AstraZeneca

Funding

AstraZeneca

Disclosure

J-C. Soria: Advisor for/honoraria received from: AstraZeneca, Eli Lilly, Genentech-Roche, MSD, Merck Serono, BMS, Pfizer, Taiho, Boehringer Ingelheim, Novartis Pharmaceuticals, GSK, Clovis Oncology Inc, Amgen Inc, Janssen, Servier and Sanofi. Y-L. Wu: Speaker fees from: AstraZeneca, Roche, Eli Lilly, Pfizer, Sanofi. K. Nakagawa: Consultant fees from: AstraZeneca, Eli Lilly. J-J. Yang: Hon. fees: AZ, Boehringer Ingelheim, Eli Lilly, Pfizer, Roche; advisor: Astellas, AZ, Bayer, Boehringer Ingelheim, Celgene, Clovis Oncology, Daiichi-Sankyo, Eli Lilly, Merck, MSD, Novartis, Pfizer, Roche/Genentech; research funding: Boehringer Ingelheim. M-J. Ahn: Advisor/consultant for: AstraZeneca, Boehringer Ingelheim, Clovis Oncology, Eli Lilly; research funding: AstraZeneca, Eli Lilly. J. Wang: Consultant fees from: AstraZeneca, Eli Lilly, Pfizer, Roche, Sanofi. J.C-H. Yang: Advisory board for Boehringer Ingelheim, Eli Lilly, Bayer, Roche/Genentech/Chugai, Astrazeneca, Astellas, MSD, Merck Serono, Pfizer, Novartis, Clovis Oncology, Celgene, innopharma, Merrimack. Y. Lu: Consultant fees from: AstraZeneca, Eli Lilly, Roche, Pfizer; research funding: AstraZeneca, Pfizer. S. Atagi: Honoraria/consultant fees from: AstraZeneca, Eli Lilly Japan K.K., Chugai Pharmaceutical Co., Taiho Pharmaceutical Co., Boehringer Ingelheim, Pfizer Japan Inc. Y. Rukazenkov: Employee of AstraZeneca and holds shares in AstraZeneca. R. Taylor: Contractor to AstraZeneca. T.S.K. Mok: Advisor/honoraria:AZ, Roche, Eli Lilly, Merck, Eisai, BMS, AVEO, Pfizer, Taiho, Boehringer Ingelheim, Novartis, GSK, Clovis, Amgen, Janssen, BioMarin; speaker bureau:AZ, Roche, Eli Lilly, Boehringer Ingelheim, Merck, Pfizer, Amgen; research funding: AZ. All other authors have declared no conflicts of interest.