1276P - First-line treatment of advanced epidermal growth factor receptor (EGFR) mutation positive (M+) non-squamous non-small cell (NSCLC) lung cancer - a...

Date 27 September 2014
Event ESMO 2014
Session Poster Display session
Topics Anti-Cancer Agents & Biologic Therapy
Non-Small-Cell Lung Cancer, Metastatic
Personalised Medicine
Presenter John Green
Citation Annals of Oncology (2014) 25 (suppl_4): iv426-iv470. 10.1093/annonc/mdu349
Authors J.A. Green1, K. Dwan2, V. Bates3, A. Boland3, P. Jain4, J. Greenhalgh3
  • 1Institute Of Translational Medicine, University of Liverpool, L69 3BX - Liverpool/GB
  • 2Biostatistics, University of Liverpool, L693BX - Liverpool/GB
  • 3Liverpool Reviews And Implementation Group, University of Liverpool, L693BX - Liverpool/GB
  • 4Clinical Oncology, Clatterbridge Cancer Centre, CH634JY - Liverpool/GB

Abstract

Aim

To systematically review the outcome of treatment of the EGFR M+ NSCLC subtype. Measures studied are overall survival (OS), progression free survival (PFS), response and QOL/symptom control.

Methods

EGFR-targeted agents (alone or in combination with cytotoxic agents or best supportive care (BSC)) were compared with cytotoxic chemotherapy (CTX), (alone or in combination with EGFR-targeted therapies or BSC) in randomised controlled trials. All patients in the trials were CTX-naive with locally advanced or metastatic (Stage IIIB or IV) EGFR M+ NSCLC unsuitable for treatment with curative intent.

Results

Eighteen trials accruing a total of 2085 EGFR M+ patients met the inclusion criteria; 1343 were from Asian countries. Six of these trials exclusively recruited 1455 patients with EGFR M+ NSCLC, the remaining trials recruited a mixed population and reported results for patients with EGFR M+ NSCLC as subgroup analyses. Erlotinib was the intervention treatment in 8 trials, gefitinib in 6 trials, afatinib in 2 trials and cetuximab in 2 trials. Only one trial (FASTACT2; n = 97) demonstrated an OS benefit and favoured erlotinib + gemcitabine + platinum over gemcitabine + platinum. For PFS, a pooled analysis of 3 studies (EURTAC, OPTIMAL, TORCH; n = 378) demonstrated a clear benefit of erlotinib compared with CTX (HR = 0.30; 95% CI: 0.23 to 0.40). In a pooled analysis, two studies (IPASS, NEJSG; n = 491) demonstrated a clear PFS benefit of gefitinib compared with paclitaxel + carboplatin (HR = 0.39; 95% CI: 0.32 to 0.48). The two trials featuring afatinib (LUX-lung 3, LUX-lung 6; n = 709) showed a pooled PFS benefit in favour of afatanib when compared with CTX (HR = 0.42; 95% CI: 0.34 to 0.53). No statistically significant PFS benefit for cetuximab + CTX was reported in the two trials of cetuximab (FLEX, BMS099; n = 81). Commonly reported adverse events for erlotinib, gefitinib and afatinib were rash, diarrhoea and mucositis. Quality of life and symptom control were reported differently across six trials.

Conclusions

Erlotinib, gefitinib or afatinib should be the first-line treatment of choice for EGFR M+ NSCLC. Cytotoxic CTX alone is less effective than erlotinib, gefitinib or afatinib and produces greater toxicity in this population.

Disclosure

All authors have declared no conflicts of interest.