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Prognostic factors influencing overall survival in stage IV EGFR-mutant NSCLC patients treated with EGFR-TKIs

BMC Pulmonary Medicine volume 25, Article number: 114 (2025) Cite this article

Abstract

Background

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are the established first-line treatment for non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations, but survival advantages in advanced-stage cases remain modest and show interpatient variability. This study seeks to delineate real-world survival outcomes in stage IV EGFR-mutant NSCLC patients undergoing treatment with EGFR-TKIs and to identify independent prognostic factors impacting overall survival (OS). The findings are expected to be a reference for clinicians in managing advanced lung cancer patients.

Methods

Clinical characteristics from advanced EGFR-mutant NSCLC patients who received EGFR-TKIs were retrospectively analyzed to investigate the association between clinical factors and overall survival.

Results

The median OS was 40.60 months (95% confidence interval: 34.72–46.48 months), with expected 1-, 3-, and 5-year OS of 87.2%, 57.8%, and 34.0%, respectively. Patients exhibiting specific characteristics, such as being under 60 years old, having stage IVA disease, adenocarcinoma histology, no liver or brain metastases, negative for neuron-specific enolase (NSE), carcinoembryonic antigen (CEA), cytokeratin fragment 19 (CYFRA 21 − 1), progastrin-releasing peptide (ProGRP), and those who received chemotherapy and radiotherapy exhibited significantly longer survival times compared to patients with the opposite characteristics (being 60 years or older, having stage IVB or IVC disease, non-adenocarcinoma histology, presence of liver or brain metastases, positive for CEA, NSE, ProGRP, CYFRA 21 − 1, and not receiving chemotherapy or radiotherapy) (P < 0.05). Cox univariate and multivariate analyses identified pathological type, liver metastasis, brain metastasis, NSE, CYFRA 21 − 1, EGFR-TKIs type, radiotherapy, and chemotherapy as independent prognostic factors for patients with stage IV NSCLC treated with EGFR-TKIs.

Conclusions

Pathological type, liver metastasis, brain metastasis, NSE, and CYFRA 21 − 1 were identified as independent risk factors for stage IV NSCLC patients treated with EGFR-TKIs, while chemotherapy and radiotherapy were determined to be independent protective factors. Taking icotinib or gefitinib, as opposed to osimertinib, was an independent risk factor for advanced NSCLC patients.

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Introduction

Non-small cell lung cancer (NSCLC) is the predominant form of lung cancer and is typically linked to a poor prognosis [1]. At initial diagnosis, 46.8–61.2% of NSCLC patients identified as having stage IV disease [2]. Stage IV NSCLC is generally considered incurable, with palliative care serving as the cornerstone of management [2]. However, advancements in precision medicine for advanced NSCLC have introduced a range of tyrosine kinase inhibitor regimens. Despite the expansion of treatment options, the prognosis for NSCLC remains unfavorable [3].

Gefitinib, the first clinically approved epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), demonstrates efficacy in patients with 19del and L858R mutations, but resistance emerges rapidly [4]. Icotinib, China’s first independently developed EGFR-TKI, shares structural similarities with gefitinib but demonstrates lower toxicity and improved tolerability [5]. Osimertinib, known as a third-generation EGFR-TKI, is now regarded as the standard initial treatment for metastatic NSCLC with EGFR mutations, demonstrating high selectivity towards both sensitive EGFR mutations and T790M resistance [6].

Previous studies have demonstrated that, although advanced patients harbor specific EGFR mutations, the survival benefits may still be limited for some. Moreover, the degree of benefit from EGFR-TKI treatment varies among individuals, suggesting the influence of additional prognostic factors in EGFR-TKI-treated patients [7, 8].

Therefore, this research was performed to identify factors influencing the prognosis of individuals with advanced EGFR-mutant NSCLC receiving EGFR-TKIs, aiming to provide more reliable reference information for clinical diagnosis and prognosis assessment.

Methods

Patients

This research analyzed advanced NSCLC patients with EGFR mutations, diagnosed at Tongji Hospital, from November 1, 2014, to November 1, 2023, and patients were collected consecutively. Eligible patients were diagnosed with stage IV NSCLC through endobronchial ultrasound-guided transbronchial needle aspiration biopsy, fibreoptic bronchoscopy, percutaneous lung biopsy, or postoperative pathological examination. Genetic testing confirmed EGFR mutations, and patients were treated with first-line EGFR-TKIs, including osimertinib (80 mg daily), gefitinib (250 mg daily), or icotinib (125 mg three times daily). Exclusion criteria included patients with other primary malignancies, loss to follow-up, or incomplete medical records, resulting in a final sample size of 461. Up to the end of the research period (June 12, 2024), the survival or death statuses of the patients were recorded, and the patients who were still alive were recorded as censored data.

Patient staging was conducted in accordance with the ninth edition of the TNM classification system for lung cancer. The study was approved by the Ethics Committee and Institutional Review Board of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology (TJ-IRB202408023).

Data collection

Clinical data were obtained through patient charts, including age, sex, staging, smoking history, hypertension, diabetes, coronary artery disease and pathological type. Details on metastasis were also recorded, encompassing pleural, brain, hepatic, adrenal, bone, intrapulmonary metastasis, malignant pleural effusion, and other metastases. In addition, lung cancer biomarkers such as neuron-specific enolase (NSE), carcinoembryonic antigen (CEA), cytokeratin fragment 19 (CYFRA 21 − 1), squamous cell carcinoma antigen (SCC), and progastrin-releasing peptide (ProGRP), along with genetic testing results and treatment-related variables, were recorded. Treatments included using EGFR-TKIs, immunotherapy, lung surgery, metastasis surgery, radiotherapy, and chemotherapy. Follow-up information was collected through telephone interviews or medical records. The cut-off values for tumor markers were set as follows: NSE at 16.3 µg/L, CEA at 5.0 ng/mL, CYFRA 21 − 1 at 3.3 µg/L, SCC at 1.5 ng/mL, and ProGRP at 65.7 pg/mL, based on the upper limits of normal test values at Tongji Hospital.

Data analysis

The chi-square test was employed to analyze categorical variables. OS was assessed, and survival curves were generated using the Kaplan-Meier method, with comparisons made via the log-rank test. The time-dependent covariate method was used to test the equal proportional risk of all variables (see Additional file 1). Univariate and multivariate Cox proportional hazards models were developed. Variables with a P-value below 0.05 in the univariate analysis were included in the multivariate model. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated. Statistical significance was defined as a P-value < 0.05. All analyses were conducted using SPSS 27.0 (SPSS Inc., Chicago, IL, USA), and a forest plot was created with GraphPad Prism 8 (GraphPad Software, CA, USA).

Results

Basic characteristics of patients

The study enrolled 461 patients with advanced NSCLC, of which 257 (55.7%) were female. The cohort’s median age was 58, with 259 patients (56.2%) classified as stage IVA. The histological analysis identified 444 cases (96.3%) as adenocarcinoma and 17 cases (3.7%) as non-adenocarcinoma, including seven adenosquamous, seven squamous, and three pulmonary sarcomatoid carcinomas. Genetic analysis revealed that 242 patients (52.5%) harbored 19del mutations, 183 (39.7%) carried L858R mutations, and 36 (7.8%) exhibited other types of EGFR mutations. Comprehensive details regarding the patients’ clinical information are provided (Table 1).

Table 1 Basic characteristics of patients
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Survival of stage IV EGFR-mutant NSCLC patients

Across the follow-up duration, 233 patients (50.5%) died. The overall cohort had a median OS of 40.60 months (95% CI: 34.72–46.48 months), with estimated 1-, 3-, and 5-year OS of 87.2%, 57.8%, and 34.0%, respectively (Fig. 1).

Fig. 1
figure 1

Survival of stage IV EGFR-mutant NSCLC patients. mOS, median overall survival

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The study results demonstrated that patients with specific characteristics (age < 60 years, stage IVA, adenocarcinoma, absence of liver metastasis, absence of brain metastasis, CEA-negative, NSE-negative, ProGRP-negative, CYFRA 21-1-negative, receiving radiotherapy, receiving chemotherapy, and receiving osimertinib) had significantly longer survival than those with opposite characteristics (age ≥ 60 years, stages IVB or IVC, non-adenocarcinoma, presence of liver and brain metastasis, CEA-positive, NSE-positive, ProGRP-positive, CYFRA 21-1-positive, not receiving radiotherapy, not receiving chemotherapy, and receiving icotinib or gefitinib) (Table 2), (Fig. 2). Kaplan-Meier curves with no significant differences in other subgroups are provided as additional files (P ≥ 0.05) (Additional file 2).

Table 2 Comparison of overall survival in patients with stage IV EGFR-mutant NSCLC
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Fig. 2
figure 2

Kaplan-Meier survival curves for overall survival in different subgroups of stage IV NSCLC patients. CEA, carcinoembryonic antigen; CYFRA 21 − 1, cytokeratin-19 fragments; EGFR-TKIs, epidermal growth factor receptor tyrosine kinase inhibitors; NSE, neuron-specific enolase; ProGRP, progastrin-releasing peptide

Full size image

COX univariate and multivariate analyses

Cox univariate analysis identified age, stage, pathology type, liver metastasis, brain metastasis, CEA, NSE, ProGRP, CYFRA 21 − 1, EGFR-TKIs, radiotherapy, and chemotherapy as significant factors (P < 0.050). Based on these findings, a multivariate Cox model was constructed, revealing that pathology type, liver metastasis, brain metastasis, NSE, CYFRA 21 − 1, EGFR-TKIs, radiotherapy, and chemotherapy remained significant. These results suggest that pathology type, liver metastasis, brain metastasis, NSE, and CYFRA 21 − 1 serve as distinct risk factors for advanced NSCLC patients. Radiotherapy and chemotherapy serve as independent protective factors. Additionally, using icotinib or gefitinib was identified as a distinct risk factor compared to using osimertinib for advanced NSCLC patients (Table 3).

Table 3 COX univariate and multivariate analyses in patients with EGFR-mutant stage IV NSCLC
Full size table

Differences in sex, age, and staging in the association between EGFR-TKIs and death

To further investigate potential differences in the association between EGFR-TKIs and mortality among advanced NSCLC patients by sex, age, and stage, separate subgroup analyses were performed according to these variables. The results indicated that among female patients, treatment with icotinib (HR = 2.16, 95% CI: 1.33–3.50, P = 0.002) and gefitinib (HR = 2.00, 95% CI: 1.07–3.74, P = 0.029) was significantly related to a higher risk of mortality than treatment with osimertinib. This association was insignificant among male patients receiving gefitinib or icotinib compared to those taking osimertinib. However, among male patients, treatment with icotinib was associated with a significantly higher risk of death compared to osimertinib (HR = 2.99, 95% CI: 1.65–5.42, P < 0.001).

Among patients under 60, those treated with icotinib had a significantly higher risk of death compared to those receiving osimertinib (HR = 2.61, 95% CI: 1.56–4.36, P < 0.001). This association was not significant for patients treated with gefitinib. In patients aged 60 or above, treatment with icotinib was related to a higher risk of death than osimertinib (HR = 2.46, 95% CI: 1.39–4.35, P = 0.002), while gefitinib use was also linked to a higher risk of death than osimertinib (HR = 2.74, 95% CI: 1.39–5.39, P = 0.004).

Among patients with stage IVA, treatment with icotinib (HR = 3.19, 95% CI: 1.78–5.71, P < 0.001) or gefitinib (HR = 2.30, 95% CI: 1.14–4.63, P = 0.020) was strongly linked to a higher risk of mortality than osimertinib. In stage IVB or IVC patients, icotinib use was also markedly related to an increased risk of death compared to osimertinib (HR = 2.34, 95% CI: 1.43–3.82, P < 0.001) (Fig. 3).

Fig. 3
figure 3

Differences in sex, age, and staging between osimertinib and other EGFR-TKIs in the Cox proportional hazard model. CI, confidence interval; HR, hazard ratio

Full size image

Discussion

With advancements in precision and personalized medicine, it is essential to research stage IV NSCLC patients with EGFR mutations. Assessing the prognostic impact of patients’ clinical characteristics on EGFR-TKI treatment can provide more reliable reference information for clinical diagnosis, treatment, and prognosis assessment, supporting clinicians in making more informed treatment choices.

Patients with non-adenocarcinomas exhibit a lower prevalence of EGFR mutations than those with lung adenocarcinomas, with rates typically between 0% and 20% [9]. Among patients harboring EGFR mutations, non-adenocarcinoma exhibited a shorter PFS (Progression-free survival) than adenocarcinoma (4.60 vs. 11.00 months, P < 0.001), while OS was not assessed [10]. Adenocarcinoma histology is a distinct predictor of improved outcomes for EGFR-mutant NSCLC undergoing EGFR-TKI therapy [11, 12]. In our study, EGFR-TKI treatment resulted in longer OS for adenocarcinoma patients than non-adenocarcinoma patients.

CYFRA 21 − 1 released by cancer cells has been identified as a clinically valuable marker for detecting specific squamous lung cancers [13]. Evidence suggests that increased CYFRA 21 − 1 levels before treatment were linked to an unfavorable prognosis, regardless of the treatment regimen [14]. Takeuchi A et al. demonstrated that among individuals diagnosed with advanced NSCLC receiving EGFR-TKIs, patients exhibiting increased CYFRA 21 − 1 levels had significantly lower PFS and OS than those with normal levels [7]. Normal levels of CYFRA 21 − 1 may predict better PFS, which can be achieved by reintroducing first- and second-generation EGFR-TKIs in patients resistant to osimertinib [15]. In studies of EGFR-TKIs for EGFR-mutant NSCLC, NSE is commonly used as a marker to predict small-cell lung cancer transformation [16,17,18]. Suh KJ et al. analyzed 151 patients with EGFR-mutant NSCLC receiving gefitinib or erlotinib and found significantly shorter PFS and OS in patients with elevated NSE levels [19]. Doctors can predict patients’ better PFS based on their negative NSE before taking the drug [20]. Our study suggests that NSE negativity is a prognostic factor that predicts patients getting longer OS, but further studies may be needed to prove it.

Identifying organ metastases that impact the prognosis of individuals undergoing EGFR-TKI treatment is crucial for patient education and guiding treatment decisions. We analyzed pleural, brain, bone, adrenal, liver, and other metastases, finding that liver and brain metastases were significant prognostic factors affecting OS in advanced NSCLC. Consistent with previous reports, liver metastases were linked to a poor prognosis, with significantly lower survival compared to patients without liver metastases [21, 22]. Several researchers propose that the HGF/MET signaling pathway may contribute to this phenomenon. Increased levels of HGF have been reported in liver diseases, including various malignancies, and are frequently elevated in patients with liver metastases. As HGF-mediated c-MET activation can intensify ErbB3/PI3K/AKT signaling, liver metastases could theoretically enhance resistance to EGFR-TKIs, leading to a worse prognosis and diminished treatment response. Nonetheless, further investigations are required to confirm this hypothesis [8]. On the other hand, the lack of routine local consolidation therapy in clinical practice results in significantly deteriorated outcomes for patients presenting with liver metastases [21]. Brain metastases frequently occur in NSCLC patients, affecting approximately 25–40% of individuals, usually emerging within two years following the identification of the primary malignancy. Taniguchi Y et al. also demonstrated that brain metastases are linked to worse OS among advanced patients [23].

Previous research has indicated that osimertinib, which targets 19del, L858R, and T790M mutations, achieves superior OS and PFS compared to gefitinib and icotinib [24,25,26,27]. In summary, osimertinib is superior to gefitinib and icotinib. Our study indicated that icotinib and gefitinib were linked to poorer OS in patients with advanced-stage cancer compared to osimertinib. Subgroup analyses by sex, age, and stage revealed that the risk associated with icotinib was significantly greater than that of osimertinib. It is important to note that this study did not stratify patients who developed the T790M resistance mutation following treatment with gefitinib or icotinib and subsequently received osimertinib therapy. Therefore, the difference in OS between patients with stage IV NSCLC who initially received first-generation versus third-generation TKIs should be interpreted with caution. Longer follow-up studies and more detailed subgroup analyses are required for further evaluation.

EGFR-TKIs have demonstrated significant efficacy in oligometastatic EGFR-mutant NSCLC, but additional local radiotherapy can still provide further benefits. The phase III SINDAS trial results indicated that administering local radiotherapy to this patient group was safe and led to enhancements in PFS and OS [28]. Numerous investigations have demonstrated that integrating chemotherapy with EGFR-TKIs yields greater efficacy in advanced NSCLC [24, 29, 30]. However, this combination therapy had more adverse effects [24].

This research has certain limitations. First, it is a retrospective analysis conducted at a single institution, limited by a relatively modest sample size. Second, this study focused exclusively on OS as the sole endpoint, while PFS and therapeutic response were not investigated. Third, detailed treatment regimens of the patients were not reviewed. Fourth, some patients received third-generation EGFR-TKIs following disease progression on first-generation EGFR-TKIs. The absence of these data makes it impossible to address the concern that, had osimertinib been appropriately administered following the failure of gefitinib or icotinib, the prognosis might not have differed regardless of the initial EGFR-TKI used. However, our findings offer new insights, and additional extensive research is needed to confirm and deepen understanding of our results.

Conclusions

Unlike previous studies, the patients included were all EGFR mutant stage IV NSCLC, and we included a larger number of study populations with a longer follow-up time. So the results in this study are more appropriate for guiding the treatment of stage IV patients. This study identified pathology type, liver metastasis, brain metastasis, CYFRA 21 − 1, and NSE as independent risk factors for advanced NSCLC patients receiving EGFR-TKIs. In contrast, radiotherapy and chemotherapy were identified as independent protective factors. Regarding long-term survival, the first-line use of osimertinib seems to offer a superior prognosis in stage IV patients; however, further clinical evidence and studies are required for validation. Subgroup analyses by sex, age, and disease stage revealed that the risk linked to icotinib was notably higher than with osimertinib.

Data availability

All data generated or analysed during this study are included in this published article [and its supplementary information files].

Abbreviations

CEA:

Carcinoembryonic antigen

CI:

Confidence interval

CYFRA 21 − 1:

Cytokeratin fragment 19

EGFR:

Epidermal growth factor receptor

EGFR-TKIs:

Epidermal growth factor receptor tyrosine kinase inhibitors

HGF:

Hepatocyte growth factor

HR:

Hazard ratio

MET:

Mesenchymal-epithelial transition

NSE:

Neuron-specific enolase

NSCLC:

Non-small cell lung cancer

OS:

Overall survival

PFS:

Progression-free survival

ProGRP:

Progastrin-releasing peptide

SCC:

Squamous cell carcinoma antigen

References

  1. Guo CL, Mei JD, Jia YL, Gan FY, Tang YD, Liu CW, et al. Impact of thymosin Α1 as an Immunomodulatory therapy on long-term survival of non-small cell lung cancer patients after R0 resection: a propensity score-matched analysis. Chin Med J. 2021;134(22):2700–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Zhang C, Wang L, Li W, Huang Z, Liu W, Bao P, et al. Surgical outcomes of stage IV non-small cell lung cancer: a single-center experience. J Thorac Disease. 2019;11(12):5463–73.

    Article  Google Scholar 

  3. Yoshimura A, Uchino J, Hasegawa K, Tsuji T, Shiotsu S, Yuba T, et al. Carcinoembryonic antigen and CYFRA 21– 1 responses as prognostic factors in advanced non-small cell lung cancer. Translational Lung cancer Res. 2019;8(3):227–34.

    Article  CAS  Google Scholar 

  4. Singh S, Sadhukhan S, Sonawane A. 20 Years since the approval of first EGFR-TKI, gefitinib: insight and foresight. Biochim Et Biophys Acta Reviews cancer. 2023;1878(6):188967.

    Article  CAS  Google Scholar 

  5. Karachaliou N, Fernandez-Bruno M, Bracht JWP, Rosell R. EGFR first- and second-generation TKIs-there is still place for them in EGFR-mutant NSCLC patients. Translational cancer Res. 2019;8(Suppl 1):S23–47.

    Google Scholar 

  6. Lu S, Zhou J, Jian H, Wu L, Cheng Y, Fan Y, et al. Befotertinib (D-0316) versus Icotinib as first-line therapy for patients with EGFR-mutated locally advanced or metastatic non-small-cell lung cancer: a multicentre, open-label, randomised phase 3 study. Lancet Respiratory Med. 2023;11(10):905–15.

    Article  CAS  Google Scholar 

  7. Takeuchi A, Oguri T, Sone K, Ito K, Kitamura Y, Inoue Y, et al. Predictive and prognostic value of CYFRA 21– 1 for advanced Non-small cell lung Cancer treated with EGFR-TKIs. Anticancer Res. 2017;37(10):5771–6.

    CAS  PubMed  Google Scholar 

  8. Jiang T, Cheng R, Zhang G, Su C, Zhao C, Li X, et al. Characterization of liver metastasis and its effect on targeted therapy in EGFR-mutant NSCLC: A multicenter study. Clin Lung Cancer. 2017;18(6):631–e92.

    Article  CAS  PubMed  Google Scholar 

  9. Fukihara J, Watanabe N, Taniguchi H, Kondoh Y, Kimura T, Kataoka K, et al. Clinical predictors of response to EGFR tyrosine kinase inhibitors in patients with EGFR-mutant non-small cell lung cancer. Oncology. 2014;86(2):86–93.

    Article  CAS  PubMed  Google Scholar 

  10. Jin R, Peng L, Shou J, Wang J, Jin Y, Liang F, et al. EGFR-Mutated squamous cell lung Cancer and its association with outcomes. Front Oncol. 2021;11:680804.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Liu Y. Small cell lung cancer transformation from EGFR-mutated lung adenocarcinoma: A case report and literatures review. Cancer Biol Ther. 2018;19(6):445–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Bergqvist M, Christensen HN, Wiklund F, Bergström S. Real world utilization of EGFR TKIs and prognostic factors for survival in NSCLC during 2010–2016 in Sweden: A nationwide observational study. Int J Cancer. 2020;146(9):2510–7.

    Article  CAS  PubMed  Google Scholar 

  13. Baek AR, Seo HJ, Lee JH, Park SW, Jang AS, Paik SH, et al. Prognostic value of baseline carcinoembryonic antigen and cytokeratin 19 fragment levels in advanced non-small cell lung cancer. Cancer Biomark A. 2018;22(1):55–62.

    Article  CAS  Google Scholar 

  14. Pujol JL, Molinier O, Ebert W, Daurès JP, Barlesi F, Buccheri G, et al. CYFRA 21– 1 is a prognostic determinant in non-small-cell lung cancer: results of a meta-analysis in 2063 patients. Br J Cancer. 2004;90(11):2097–105.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Morimoto K, Yamada T, Takeda T, Shiotsu S, Date K, Tamiya N, et al. Clinical efficacy and safety of First- or Second-Generation EGFR-TKIs after osimertinib resistance for EGFR mutated lung cancer: A prospective exploratory study. Target Oncol. 2023;18(5):657–65.

    Article  PubMed  Google Scholar 

  16. Mao X, Liu J, Hu F, Niu Y, Pan F, Fu X, et al. Serum NSE is early marker of transformed neuroendocrine tumor after EGFR-TKI treatment of lung adenocarcinoma. Cancer Manage Res. 2022;14:1293–302.

    Article  CAS  Google Scholar 

  17. Chen X, Li D, Miao K, Shou T, Zhang W. Small cell lung cancer transformation after EGFR-TKIs treatment in lung adenocarcinoma: A case report and literatures review. Medicine. 2023;102(4):e32697.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Jiang Y, Shou L, Guo Q, Bao Y, Xu X, An S, et al. Small-cell lung cancer transformation from EGFR-mutant adenocarcinoma after EGFR-TKIs resistance: A case report. Medicine. 2021;100(32):e26911.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Suh KJ, Keam B, Kim M, Park YS, Kim TM, Jeon YK, et al. Serum Neuron-Specific enolase levels predict the efficacy of First-Line epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors in patients with Non-Small cell lung Cancer harboring EGFR mutations. Clin Lung Cancer. 2016;17(4):245–e521.

    Article  CAS  PubMed  Google Scholar 

  20. Dong J, Tong S, Shi X, Wang C, Xiao X, Ji W, et al. Progastrin-Releasing peptide precursor and Neuron-Specific enolase predict the efficacy of First-Line treatment with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors among Non-Small-Cell lung Cancer patients harboring EGFR mutations. Cancer Manage Res. 2020;12:13607–16.

    Article  CAS  Google Scholar 

  21. Castañón E, Rolfo C, Viñal D, López I, Fusco JP, Santisteban M, et al. Impact of epidermal growth factor receptor (EGFR) activating mutations and their targeted treatment in the prognosis of stage IV non-small cell lung cancer (NSCLC) patients harboring liver metastasis. J Translational Med. 2015;13:257.

    Article  Google Scholar 

  22. Chang YP, Chen YM, Lai CH, Lin CY, Fang WF, Huang CH, et al. The impact of de Novo liver metastasis on clinical outcome in patients with advanced non-small-cell lung cancer. PLoS ONE. 2017;12(6):e0178676.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Taniguchi Y, Tamiya A, Nakahama K, Naoki Y, Kanazu M, Omachi N, et al. Impact of metastatic status on the prognosis of EGFR mutation-positive non-small cell lung cancer patients treated with first-generation EGFR-tyrosine kinase inhibitors. Oncol Lett. 2017;14(6):7589–96.

    PubMed  PubMed Central  Google Scholar 

  24. Noronha V, Patil VM, Joshi A, Menon N, Chougule A, Mahajan A, et al. Gefitinib versus gefitinib plus pemetrexed and carboplatin chemotherapy in EGFR-Mutated lung Cancer. J Clin Oncology: Official J Am Soc Clin Oncol. 2020;38(2):124–36.

    Article  CAS  Google Scholar 

  25. Shi YK, Wang L, Han BH, Li W, Yu P, Liu YP, et al. First-line Icotinib versus cisplatin/pemetrexed plus pemetrexed maintenance therapy for patients with advanced EGFR mutation-positive lung adenocarcinoma (CONVINCE): a phase 3, open-label, randomized study. Annals Oncology: Official J Eur Soc Med Oncol. 2017;28(10):2443–50.

    Article  CAS  Google Scholar 

  26. Ramalingam SS, Vansteenkiste J, Planchard D, Cho BC, Gray JE, Ohe Y, et al. Overall survival with osimertinib in untreated, EGFR-Mutated advanced NSCLC. N Engl J Med. 2020;382(1):41–50.

    Article  CAS  PubMed  Google Scholar 

  27. Soria JC, Ohe Y, Vansteenkiste J, Reungwetwattana T, Chewaskulyong B, Lee KH, et al. Osimertinib in untreated EGFR-Mutated advanced Non-Small-Cell lung Cancer. N Engl J Med. 2018;378(2):113–25.

    Article  CAS  PubMed  Google Scholar 

  28. Wang XS, Bai YF, Verma V, Yu RL, Tian W, Ao R, et al. Randomized trial of First-Line tyrosine kinase inhibitor with or without radiotherapy for synchronous oligometastatic EGFR-Mutated Non-Small cell lung Cancer. J Natl Cancer Inst. 2023;115(6):742–8.

    Article  CAS  PubMed  Google Scholar 

  29. Gu W, Zhang H, Lu Y, Li M, Yang S, Liang J, et al. EGFR-TKI combined with pemetrexed versus EGFR-TKI monotherapy in advanced EGFR-mutated NSCLC: A prospective, randomized, exploratory study. Cancer Res Treat. 2023;55(3):841–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Jänne PA, Planchard D, Kobayashi K, Cheng Y, Lee CK, Valdiviezo N et al. CNS efficacy of osimertinib with or without chemotherapy in epidermal growth factor Receptor-Mutated advanced Non-Small-Cell lung Cancer. J Clin Oncology: Official J Am Soc Clin Oncol. 2023:Jco2302219.

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Authors and Affiliations

  1. Department of Thoracic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Avenue, Qiaokou District, Wuhan, 430030, China

    Linwu Kuang, Yuchen Zhang, Peng Wang & Yangkai Li

  2. Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

    Hao Wang

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Contributions

(I) Conception and design: L.W. Kuang; (II) Administrative support: All authors; (III) Provision of study materials or patients: All authors; (IV) Collection and assembly of data: All authors; (V) Data analysis and interpretation: L.W. Kuang; (VI) Manuscript writing: L.W. Kuang; (VII) Final approval of manuscript: All authors.

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Correspondence to Yangkai Li.

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All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000. The study was approved by the Medical Ethics Committee of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology(TJ-IRB202408023). Given that this was a retrospective study, the written informed consent was waived and the verbal informed consent has been approved by the Medical Ethics Committee of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology. We informed all participants during the telephone follow-up and obtained their verbal informed consent.

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Kuang, L., Zhang, Y., Wang, H. et al. Prognostic factors influencing overall survival in stage IV EGFR-mutant NSCLC patients treated with EGFR-TKIs. BMC Pulm Med 25, 114 (2025). https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s12890-025-03569-1

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  • DOI: https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s12890-025-03569-1

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BMC Pulmonary Medicine

ISSN: 1471-2466

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