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

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Abstract

Non-small cell lung cancer (NSCLC) patients harboring KRAS mutation were associated with worse prognosis and lower response to epidermal growth factor receptor (EGFR) target therapy than those with wild-type tumors. However, whether the underlying biological differences are associated with the efficacy of cytotoxic chemotherapy in advanced NSCLC patients remained controversial. We searched electronic databases for eligible literatures. The primary outcomes were objective response rate (ORR), 6-month and 1-year progression-free survival (PFS) rate. The pooled odds ratio (OR) was calculated using random-effect model. Subgroup analyses stratified by literature type, mutation analysis method, therapeutic regimen, patient origin, and EGFR mutation status in KRAS wild-type patients were proposed. Heterogeneity and publication bias were quantitatively evaluated. A total of ten studies involving 1,677 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 6-month (51.0 vs. 56.8 %) and 1-year (10.3 vs. 13.3 %) PFS rate than wild-type patients, but there was no significant difference between the two groups (OR 0.75, 95 % CI 0.54–1.04, P = 0.08; OR 0.75, 95 % CI 0.47–1.21, P = 0.25). Results of the subgroup analyses were almost concordant with the overall ones. This comprehensive analysis revealed that advanced NSCLC patients with KRAS mutations had significantly lower ORR and potentially lower 6-month/1-year PFS rate compared with wild-type patients after first-line chemotherapy.

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Abbreviations

NSCLC:

Non-small cell lung cancer

EGFR:

Epidermal growth factor receptor

ORR:

Objective response rate

PFS:

Progression-free survival

OR:

Odds ratio

EML4:

Echinoderm microtubule-associated protein-like 4

ALK:

Anaplastic lymphoma kinase

EGFR-TKI EGFR:

Tyrosine kinase inhibitors

ACT:

Adjuvant chemotherapy

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Acknowledgments

This study was supported by the following funds: (1) National High Technology Research and Development Program of China (Grant No. 2012AA02A502). (2) Innovative drug R&D center based on real-time high-throughput cell-based screening platform and large capacity compound library (Grant No. 2013ZX09401003-002). (3) National Natural Science Funds of China (Grant No. 81372502). (4) Wu Jieping Medical Foundation Project (Grant No. 320.6750.131). All the funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Conflict of interest

The authors have declared no conflicts of interest.

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    Authors and Affiliations

    1. State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China

      Yaxiong Zhang, Wenfeng Fang, Yue Yan, Mengyao Wang, Shiyang Kang, Jin Sheng, Jianhua Zhan, Nan Chen, Shaodong Hong, Yunpeng Yang, Yuxiang Ma, Dacheng He, Tao Qin, Ting Zhou, Yanna Tang & Xiaobo He

    2. Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China

      Yaxiong Zhang, Mengyao Wang, Shiyang Kang & Dacheng He

    3. Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng Road East, Guangzhou, 510060, Guangdong, People’s Republic of China

      Wenhua Liang & Li Zhang

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    Correspondence to Wenhua Liang or Li Zhang.

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    Yaxiong Zhang, Wenfeng Fang, Yue Yan and Mengyao Wang have contributed equally to this work.

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    Zhang, Y., Fang, W., Yan, Y. et al. The efficacy of first-line chemotherapy is associated with KRAS mutation status in patients with advanced non-small cell lung cancer: a meta-analysis. Med Oncol 32, 61 (2015). https://doi.org/10.1007/s12032-015-0489-y

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