LBA2_PR - Gefitinib/chemotherapy vs chemotherapy in epidermal growth factor receptor (EGFR) mutation-positive non-small-cell lung cancer (NSCLC) after progre...

Date 28 September 2014
Event ESMO 2014
Session Presidential Symposium 1
Topics Anti-Cancer Agents & Biologic Therapy
Non-Small-Cell Lung Cancer, Metastatic
Personalised Medicine
Presenter Tony Mok
Citation Annals of Oncology (2014) 25 (5): 1-41. 10.1093/annonc/mdu438
Authors T.S.K. Mok1, Y. Wu2, K. Nakagawa3, S. Kim4, J. Yang5, M. Ahn6, J. Wang7, J. Yang8, Y. Lu9, S. Atagi10, S. Ponce11, X. Shi12, A. Webster13, H. Jiang12, J. Soria14
  • 1Clinical Oncology, The Chinese University of Hong Kong, . - Hong Kong/CN
  • 2Guangdong Lung Cancer Institute, Guangdong General Hospital and Guangdong Academy of Medical Sciences, . - Guangzhou/CN
  • 3Department Of Medical Oncology, School of Medicine, Kinki University, . - Osakasayama City/JP
  • 4Department Of Medicine, Asan Medical Center, University of Ulsan College of Medicine, . - Seoul/KP
  • 5Department Of Medicine, Guangdong General Hospital., Guangdong Lung Cancer Institute, 510080 - Guangzhou/CN
  • 6Division Of Hematology-oncology,department Of Medicine, Samsung Medical Center Sungkyunkwan University School of Medicine, . - Seoul/KP
  • 7Department Of Thoracic Medical Oncology, Peking University, School of Oncology, Beijing Cancer Hospital and Institute, . - Beijing/CN
  • 8Department Of Oncology, National Taiwan University Hospital, TW-100 - Taipei/TW
  • 9Department Of Thoracic Cancer, Cancer Center, West China Hospital, West China Medical School, Sichuan University, . - Sichuan/CN
  • 10Department Of Internal Medicine, National Kinki Central Hospital for Chest Diseases, Osaka/JP
  • 11Medical Oncology Service, Hospital Universitario 12 de Octubre, Madrid/ES
  • 12N/a, Astra Zeneca, Shanghai/CN
  • 13N/a, Astra Zeneca, . - Macclesfield/GB
  • 14Dept. Of Medicine, Institut Gustave Roussy, FR-94805 - Villejuif/FR

Abstract

Aim

Most patients (pts) with EGFR mutation-positive NSCLC respond to 1st-line EGFR tyrosine kinase inhibitors, but later acquire resistance. The Phase III, double-blind IRESSA Mutation Positive Multicentre Treatment Beyond ProgRESsion Study (IMPRESS; NCT01544179) evaluated the efficacy/safety of continuing gefitinib plus cisplatin/pemetrexed (cis/pem) (G) vs placebo plus cis/pem (P) in pts with acquired resistance to 1st-line gefitinib.

Methods

Pts (age ≥18 years [Japan ≥20 years], chemotherapy-naïve, locally advanced/metastatic NSCLC with an activating EGFR mutation, prior disease progression on 1st-line gefitinib) from 71 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: progression-free survival (PFS). Secondary endpoints included: overall survival (OS), objective response rate (ORR), disease control rate (DCR) and safety/tolerability.

Results

265 pts randomised (G = 133; P = 132). There was no statistically significant improvement in PFS for G vs P (hazard ratio [HR] 0.86; 95% confidence interval [CI] 0.65–1.13, p = 0.273; median PFS 5.4 months each).OS was immature (33% of pts had died), with better OS for P vs G suggested (statistically significant difference: HR 1.62; CI 1.05–2.52, p = 0.029). No treatment differences were found in ORR/DCR. Most common adverse events (AEs) in the safety population (G/P both n = 132): nausea (64%/61%) and decreased appetite (49%/34%); no interstitial lung disease noted. G was associated with increased grade 1/2 gastrointestinal toxicities. AEs with outcome of death reported: with G, 2 casually-related to gefitinib and/or cis/pem; with P, 1 casually-related to cis/pem.

Conclusions

IMPRESS is the first and only randomised Phase III study to confirm continuation of gefitinib in addition to cis/pem would be of no clinical benefit for pts with acquired resistance to gefitinib; thus the standard of care should remain doublet chemotherapy alone. The safety profile for gefitinib plus cis/pem was in line with that known.

Disclosure

T.S.K. Mok: AstraZeneca, Roche, Eli Lilly, Merck Serono, Eisai, BMS, AVEO, Pfizer, Taiho, Boehringer Ingelheim, Novartis, GSK Biologicals, Clovis Oncology Inc, Amgen Inc, Janssen, BioMarin Inc, Roche, Eli Lilly, Merck Serono, Amgen International; Y. Wu: Speaker fees from: AstraZeneca, Roche, Eli Lilly, Pfizer, Sanofi K. Nakagawa: Consultant fees from: AstraZeneca, Eli Lilly; S. Kim: Advisor for: Boehringer Ingelheim; ISS drug supply: AstraZeneca, Boehringer Ingelheim, Eli Lilly; M. Ahn: Advisor/consultant for: AstraZeneca, Boehringer Ingelheim, Clovis Oncology, Eli Lilly; research funding: AstraZeneca, Eli Lilly; J.C. Yang: Advisory fees from: AstraZeneca, Roche, Genentech, Pfizer, Clovis; uncompensated advisor for: Boehringer Ingelheim, Eli Lilly; Y. Lu: Consultant fees from: AstraZeneca, Eli Lilly, Roche, Pfizer; research funding: AstraZeneca, Pfizer; S. Atagi: Honoraria/consultant fees from: Eli Lilly Japan K.K., Chugai Pharmaceutical Co., Taiho Pharmaceutical Co., Boehringer Ingelheim, Pfizer Japan Inc.; X. Shi, A. Webster and H. Jiang: Employee of AstraZeneca and holds shares in AstraZeneca; J-C. Soria: Consultant fees from: AstraZeneca, Eli Lilly. All other authors have declared no conflicts of interest.