Tony Mok, The Chinese University of Hong Kong, Shatin, China
Gefitinib/chemotherapy vs chemotherapy in epidermal growth factor receptor (EGFR) mutation-positive non-small-cell lung cancer (NSCLC) after progression on first-line gefitinib: the Phase III, randomised IMPRESS study:
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.