Response to first-line chemotherapy in patients with non-small-cell lung cancer according to epidermal growth factor receptor and K-RAS mutation status
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Updated: May 1, 2026
Establishing Dual Resistance to EGFR-TKI and MET-TKI in Lung Adenocarcinoma Cells In Vitro with a 2-step Dose-escalation Procedure
Published on: August 11, 2017
Xiaopeng Dong1, Xiaogang Zhao, Yingtao Hao
1Department of Thoracic Surgery, Second Hospital of Shandong University, Jinan, China.
Background:
Epidermal growth factor receptor (EGFR)-targeted therapy has shown a favorable efficacy in patients with non-small-cell lung cancer (NSCLC). Conversely, K-RAS mutations were reported to have an adverse effect on the survival of patients with NSCLC. These studies suggest that the tumor biology of patients with EGFR or K-RAS mutations is different from that of patients with wild-type mutations. Therefore, we hypothesized that the response to cytotoxic chemotherapy may differ among patients with and without EGFR or K-RAS mutations.
Methods:
A total of 229 patients with advanced NSCLC who received platinum doublet chemotherapy were included in this retrospective study, and their clinical outcomes were analyzed according to EGFR and K-RAS mutation status.
Results:
EGFR and K-RAS mutations were found in 52.4% and 27.9% of patients, respectively. Progression-free survival (PFS) was significantly higher in patients with EGFR mutations than in patients with wild-type EGFR (P = .008), and multivariate analysis showed that EGFR mutation was an independent factor to chemotherapy (P = .01). Among the patients with EGFR mutations, the disease control rate for docetaxel was higher than for gemcitabine-based therapy (P = .031). In addition, docetaxel or vinorelbine showed a longer PFS than gemcitabine-based chemotherapy in patients with EGFR mutations (P = .033 and P = .028). However, no similar differences were found according to the K-RAS mutations.
Conclusions:
EGFR, but not K-RAS mutation, is associated with improved survival time to platinum-based chemotherapy. In patients with EGFR mutations, PFS for docetaxel and gemcitabine was higher than for vinorelbine-based chemotherapies. The predictive meaning of EGFR mutation for chemotherapy should be further investigated.
Insights
Epidermal growth factor receptor (EGFR) mutations, but not K-RAS mutations, predict better outcomes for non-small-cell lung cancer patients receiving chemotherapy. Docetaxel and vinorelbine showed improved progression-free survival in patients with EGFR mutations.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Epidermal growth factor receptor (EGFR) targeted therapy shows efficacy in non-small-cell lung cancer (NSCLC).
- K-RAS mutations are associated with poorer survival in NSCLC patients.
- Tumor biology differs between EGFR/K-RAS mutated and wild-type NSCLC, suggesting varied responses to chemotherapy.
Purpose of the Study:
- To investigate the differential response to cytotoxic chemotherapy based on EGFR and K-RAS mutation status in advanced NSCLC patients.
- To determine if EGFR or K-RAS mutations impact clinical outcomes in NSCLC treated with platinum doublet chemotherapy.
Main Methods:
- Retrospective analysis of 229 advanced NSCLC patients treated with platinum doublet chemotherapy.
- Clinical outcomes were analyzed based on EGFR and K-RAS mutation status.
Main Results:
- EGFR mutations occurred in 52.4% and K-RAS in 27.9% of patients.
- EGFR mutations were associated with significantly higher progression-free survival (PFS) and were an independent predictor of chemotherapy response (P = .01).
- In EGFR-mutated patients, docetaxel showed higher disease control rates and longer PFS compared to gemcitabine-based or vinorelbine-based chemotherapy; K-RAS mutations did not show similar associations.
Conclusions:
- EGFR mutation status, unlike K-RAS, is linked to improved survival with platinum-based chemotherapy in NSCLC.
- Specific chemotherapies like docetaxel and vinorelbine may offer better PFS in EGFR-mutated NSCLC patients.
- The predictive value of EGFR mutations for chemotherapy response warrants further investigation.
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