1301P - The efficacy of first-line chemotherapy is associated with KRAS mutation status in patients with advanced non-small cell lung cancer: A meta-analysis

Date 27 September 2014
Event ESMO 2014
Session Poster Display session
Topics Anti-Cancer Agents & Biologic Therapy
Non-Small-Cell Lung Cancer, Metastatic
Pathology/Molecular Biology
Translational Research
Presenter Yaxiong Zhang
Citation Annals of Oncology (2014) 25 (suppl_4): iv426-iv470. 10.1093/annonc/mdu349
Authors Y. Zhang, L. Zhang, W. Liang, M. Wang, S. Kang, W. Fang, X. Wu, S. Hong, J. Sheng
  • Department Of Medical Oncology, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, 510060 - Guangzhou/CN

Abstract

Aim

Non-small-cell lung cancer (NSCLC) patients harboring KRAS mutations were associated with worse prognosis and lower response to epidermal growth factor receptor (EGFR) targeted therapy including EGFR tyrosine kinase inhibitors (EGFR-TKIs) and anti-EGFR monoclonal antibodies than those with wild-type tumors. However, whether the underlying biological differences are associated with the efficacy of cytotoxic chemotherapy in advanced NSCLC patients remains controversial. Thus, we sought to perform a meta-analysis incorporating all available evidences to evaluate the clinical outcome according to the KRAS mutation status in patients with advanced NSCLC treated with front-line conventional chemotherapy.

Methods

We searched electronic databases for eligible literature. The primary outcomes were objective response rate (ORR), six-month and one-year progression-free survival (PFS) rate. The pooled odds ratio (OR) was calculated using random-effects model. Subgroup analyses stratified by literature type, mutation analysis method, therapeutic regimen, patient origin, EGFR mutation status in KRAS wild-type patients were proposed. All calculations were performed using REVIEW MANAGER version 5.0. Heterogeneity and publication bias were quantitatively evaluated.

Results

A total of 10 studies involving 1677 advanced NSCLC patients with known KRAS mutation status who had received first-line chemotherapy were included. KRAS mutants had lower ORR than wild-type patients (25.1% vs. 34.4%) significantly (OR 0.67, 95% CI 0.50-0.88, P = 0.004). Additionally, patients with KRAS mutation had numerically lower six-month (51.0% vs. 56.8%) and one-year (10.3% vs. 13.3%) PFS rate than wild-type patients, but there was no significant difference between the two groups (Six-month PFS: OR 0.75, 95% CI 0.54-1.04, P = 0.08; One-year PFS: OR 0.75, 95% CI 0.47-1.21, P = 0.25). Results of the subgroup analyses were almost concordant with the overall ones.

Conclusions

This comprehensive analysis revealed that advanced NSCLC patients with KRAS mutations had significantly lower ORR and potentially lower six-month/one-year PFS rates compared with wild-type patients after first-line chemotherapy. KRAS mutation status should be considered as an essential factor in studies regarding chemotherapy regimens or other non-targeted agents.

Disclosure

All authors have declared no conflicts of interest.