Trials investigating the efficacy of EGFR-tyrosine kinase inhibitors (TKIs) in combination with chemotherapy in unselected patients with advanced non-small-cell lung cancer (NSCLC) showed negative results. Preclinical data suggest that the intercalated administration could be effective. The aim of our study was to perform a systematic review and meta-analysis of randomized trials (RCTs) testing the addition of intercalated EGFR-TKIs to chemotherapy in patients with advanced NSCLC.
A systematic review of articles published or presented at major meetings was performed in December 2015. RCTs comparing CT + intercalated EGFR TKI vs. CT alone in pts with advanced NSCLC were included. The primary outcome measure was overall survival (OS); secondary outcomes were progression-free survival (PFS), objective response rate (ORR) and toxicity.
9 RCTs were eligible (5 with erlotinib, 4 with gefitinib): 37% of patients had known EGFR mutational status, and 46% were EGFR mutation-positive. Intercalated combination was associated with a significant improvement in OS (Hazard Ratio [HR] 0.83, 95%CI 0.72-0.97, p = 0.02), PFS (HR 0.60, 95%CI 0.53-0.68, p
The addition of intercalated EGFR-TKI to chemotherapy is associated with a significant benefit in OS, PFS and objective response rate in patients with advanced NSCLC, although a definitive interpretation is jeopardized by the variable proportion of patients with EGFR mutation-positive tumors included.
Clinical trial identification
Legal entity responsible for the study
University of Turin
University of Turin
A. Rossi: Honoraria as speaker bureau for Roche, BoehringerIngelheim, AstraZeneca, and advisory board member for AstraZeneca and Eli-Lilly. D. Galetta: Advisory board member for BoehringerIngelheim and Eli-Lilly. S. Novello: Honoraria as speaker bureau for Roche, BoehringerIngelheim, AstraZeneca, and Eli-Lilly. M. Di Maio: Honoraria as speaker bureau for BoehringerIngelheim, AstraZeneca, Eli-Lilly and advisory board member for AstraZeneca and Eli-Lilly. All other authors have declared no conflicts of interest.