Prevalence of EGFR mutations in patients with resected stage I–III non-small cell lung cancer: results from EARLY-EGFR Latin America study

Introduction

Lung cancer, a recognized global health problem, has emerged as a significant concern in Latin America (LATAM) countries. In 2022, the LATAM and Caribbean region witnessed 1,551,060 new cases of lung cancer, accounting for 8.1% of all the reported cancer cases and was the leading cause of cancer-related deaths with 749,242 fatalities (1). Projections for the near future are equally concerning, as the number of new lung cancer cases and deaths is expected to nearly double for women and increase by 50% for men in the region by 2030 (2). Non-small cell lung cancer (NSCLC) is the most common type, accounting for nearly 85% of all lung malignancies (3). At the time of diagnosis, nearly 30% of patients with NSCLC are identified to have early-stage disease (stage I–III) (4).

Curative treatment of early-stage NSCLC involves a surgical resection aiming at the complete eradication of loco-regional tumor to mitigate the recurrence (5). Adjuvant chemotherapy is the recommended course of action for patients with a significant risk of recurrence (6,7). Unfortunately, the rates of recurrence are substantial (35–50%) following resection (8), which emphasizes the importance of implementing effective neo-adjuvant and adjuvant treatment strategies.

Mutations in the epidermal growth factor receptor (EGFR) are reported as the most prevalent oncogene driver mutations in NSCLC (9). The in-depth understanding of the role of EGFR mutations in the pathogenesis and recurrence of NSCLC has led to the emergence of EGFR-tyrosine kinase inhibitors (TKIs), which have revolutionized the treatment of NSCLC in advanced as well as early-stage (10,11). Based on the results of the ADAURA study, adjuvant osimertinib, a third-generation EGFR-TKI (12) has now been recommended in patients with early-stage NSCLC with actionable mutations of EGFR, including exon 19 deletions or exon 21 L858R mutations (13). Hence, understanding the molecular characteristics of NSCLC, particularly EGFR mutation status, is crucial for making informed treatment decisions and achieving the best possible clinical outcomes.

Variation in the prevalence of EGFR mutations across various ethnicities has been well documented in patients with advanced NSCLC (14). In LATAM, in patients with advanced-stage NSCLC, prevalence of EGFR mutations was reported to be between 22% to 26% (15-19). However, prevalence data in early-stage NSCLC in LATAM are scarce. One recent single-center study in Brazilian patients with early-stage NSCLC reported EGFR mutation rate to be 17.3% (20). Comprehensive understanding of EGFR mutations is crucial for effective management of early-stage NSCLC. To bridge this knowledge gap, EARLY-EGFR, a prospective real-world study, was undertaken to determine the prevalence of EGFR mutations, molecular testing patterns and treatment approaches utilized for managing early-stage NSCLC in 14 countries across Asia, Middle East and Africa and LATAM. In this manuscript, we present the prevalence of EGFR mutations in the LATAM subset. We present this article in accordance with the STROBE reporting checklist (21) (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-904/rc).

Methods

Study design

EARLY-EGFR LATAM was a multicenter, non-interventional study conducted at 10 centres across 7 LATAM countries between March 2021 and October 2022. The study protocol (NCT04742192) was approved by the Independent Ethics Committee/Institutional Review Board of all participating centres in 7 countries across LATAM. Before data collection, a signed written informed consent was obtained from the patients during routine clinical care visit. The study was conducted in compliance with the International Council for Harmonization, Good Clinical Practices Guidelines and the relevant non-interventional and observational studies legislation. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by Comité Institucional de Bioética (CIB) Via Libre ethics committee (Clínica Delgado) [22 June 2021] (No. 6962-2021a). All participating centres were informed and agreed to the study.

Study population

The study enrolled consecutive patients (≥18 years old) with stage IA–IIIB [as per American Joint Committee on Cancer (AJCC) 8th edition] non-squamous NSCLC who underwent surgical resection of the tumor up to 12 weeks preceding their enrollment. Patients with formalin-fixed paraffin-embedded (FFPE) tissue specimens (either the primary diagnostic sample or the surgically resected tumor) suitable for EGFR mutation testing and accessible medical records for at least 12 months from the date of diagnosis were included. Patients with tumor histology not of primary origin in lung and those with pure squamous cell carcinoma, pure small cell carcinoma, or large cell carcinoma origin lacking immunohistochemistry evidence of adenocarcinoma differentiation, were excluded. All the FFPE samples were tested at a centralized laboratory or local laboratories.

The medical charts of eligible patients were reviewed, and the relevant data specified by the study protocol were documented in electronic case report forms before requesting the EGFR mutation testing. The results of the EGFR mutation test and other relevant tests were recorded once available. Patients’ follow-up continued until the EGFR mutation status was determined and any planned adjuvant therapy (AT) was documented. The study collected data on socio-demographics (i.e., age, gender, smoking status), clinical characteristics [i.e., Eastern Cooperative Oncology Group (ECOG) performance status, histology, stage as per AJCC 8th edition, presence of high-risk clinicopathological features], surgical management, EGFR mutation status and its different sub-types, treatment patterns, molecular testing patterns, frequency of programmed death ligand-1 (PD-L1) and other genetic test (wherever available) results.

Study outcomes

The primary outcome was the prevalence of EGFR mutations. Secondary outcomes included the proportion of patients with EGFR mutations by stage, histology, socio-demographic and clinic-pathological characteristics, EGFR mutation subtypes, molecular testing patterns, and treatment patterns.

Statistical analysis

No formal sample size was calculated for the study. Based on the precision estimates (ranging from 0 to 50%), a sample size of 600 patients was considered to be adequate for estimating the prevalence of EGFR mutations. LATAM cohort planned to enroll 80 patients, which was deemed to be adequate. The analysis was conducted using the Statistical Analysis System (SAS) (Version 9.4, SAS Institute). The data analysis involved descriptive statistics for clinico-demographic characteristics, EGFR mutation status, its subtypes, and treatment patterns. Categorical variables were expressed as frequencies and percentages, accompanied by exact 95% confidence intervals (CI) using the Clopper-Pearson method. For continuous variables, mean ± standard deviation (SD) or median (range) was used for representation. Fisher’s exact test with Monte Carlo and logistic regression was used for determining the association of categorical variables with EGFR mutation status. A P value of less than 0.05 was considered statistically significant.

Results

Demographic and clinical characteristics

A total of 80 patients were included in the LATAM subset of EARLY-EGFR study. The median (range) age of the patients was 67.0 (38.0–84.0) years, 67.5% (54/80) were females and 57.5% (46/80) were non-smokers (Table 1). Most patients had a pathologic stage IA [45.0% (36/80)] followed by stage IB [21.3% (17/80)] per AJCC 8th edition. All the patients had adenocarcinoma as the histological type, with right lung involvement in 61.3% (49/80) patients; more than half [51.2% (41/80)] patients had T1a/b/c primary tumor with no nodal involvement in 85.0% (68/80). Of available data, 95.5% (42/44) had an ECOG performance scale of ≤1. Most patients [59.7% (46/77)] had moderately differentiated (grade 2) tumors. Less than half of patients [47.2% (34/72)] were discussed at multidisciplinary team meetings.

EGFR mutation prevalence

The prevalence of EGFR mutations was found to be 39.5% (30/76) in the LATAM subset (Figure 1). Four patients failed EGFR mutation test. Almost 60% of patients had common mutations including—exon 19 deletions [overall: 33.3% (10/30); stage I: 31.6% (6/19); stage II: 42.9% (3/7); stage III: 25.0% (1/4)] and 21-L858R mutations [overall: 26.7% (8/30); stage I: 31.6% (6/19); stage II: 0; stage III: 50% (2/4)]. Uncommon mutations were identified in 33.3% (10/30) of the patients, comprising of G719X substitutions [6.7% (2/30)], INS20 [6.7% (2/30)] and other mutations [20.0% (6/30)]. In most cases [57.5% (46/80)], primary diagnostic samples were tested for EGFR mutations using real-time polymerase chain reaction (PCR)-based method [65.0% (52/80)] and next generation sequencing (NGS) panel [30.0% (24/80)] (Table S1). Most samples were tested at an external laboratory. Cobas^®EGFR mutation test v2 testing kits by Roche were used in 31.3% (n=25) and Idylla^TMEGFR Mutation Assay by Biocartis in 13.8% (n=11).

Figure 1 Overall and pathologic stage-wise EGFR mutation subtypes and compound mutations. (A) Overall EGFR mutation subtypes and compound mutations. (B) Pathologic stage-wise EGFR mutation subtypes and compound mutations.

Association between EGFR mutations and clinicopathological characteristics

A non-significantly higher percentage of patients with stage II NSCLC (47.6%) harboured EGFR mutations compared to stage I (38.0%) and stage III NSCLC (36.4%) (Table 2). The prevalence of EGFR mutations was similar between males (39.1%) and females (39.6%). Numerically higher rate of EGFR mutations was reported in patients aged >80 years compared to patients aged 60–80 years and <60 years (80.0% vs. 40.4% vs. 26.3%). Non‑smokers had a significantly higher prevalence of EGFR mutations compared to current or ex-smokers (51.2% vs. 24.2%; P=0.02).

In logistic regression analysis, age >60 years was significantly associated with higher odds of EGFR mutations compared to age <60 years [adjusted odds ratio (OR): 1.11, 95% CI: 1.04–1.19; P=0.004]. Smoking history was significantly associated with lower odds of EGFR mutations compared to current or ex-smokers (adjusted OR: 0.15, 95% CI: 0.04–0.56; P=0.005) (Table 3).

PD-L1 and other mutations

Ventana SP263 antibody was most frequently used for PD-L1 testing [90.9% (20/22)]. Among 27.5% (22/80) patients who underwent PD-L1 testing, PD-L1 expression ≥1% was reported in 36.4% (8/22) (Table 4). EGFR-mutated tumors were found to be PD-L1 positive in 36.4% (4/11) patients, all of whom reported exon 19 deletions.

Testing for other genetic mutations was performed in 28.8% (23/80) patients, majority were tested for ALK (n=23) of which 2 patients had ALK mutations (Table S2).

Treatment patterns

For the majority [overall: 76.3% (61/80); stage I: 92.5% (49/53); stage II: 56.3% (9/16); stage III: 27.3% (3/11)] of patients, no systemic therapy was planned; they underwent curative surgery alone (Figure 2). Lobectomy was the most preferred surgery type in 67.5% (54/80) of patients. Complete resection (R0) was achieved in 95.0% (76/80) of the patients. Systemic AT was planned in 21.3% (17/80) of patients, and 2 of 80 received neoadjuvant systemic therapy. Among those receiving adjuvant systemic therapy, 88.2% (15/17) received adjuvant chemotherapy (4 received cisplatin-based chemotherapy, 9 received carboplatin-based chemotherapy and 2 received other chemotherapeutic regimens), while 3 of 17 received EGFR-TKIs (2 received osimertinib and 1 received gefitinib). Per stage-wise distribution, 1 of 36 patients with stage IA, 3 of 17 patients with stage IB, 7 of 9 patients with stage IIB and 7 of 10 patients with stage IIIA were planned to receive systemic therapy. One patient with stage IIIB was also prescribed adjuvant systemic therapy. No patients with stage IIA were prescribed systemic therapy at the time of data collection.

Figure 2 Treatment patterns in early-stage (stage I–III) NSCLC. NSCLC, non-small cell lung cancer.

Discussion

In LATAM, lung cancer is the third leading cause of cancer deaths. For optimum clinical care of patients with NSCLC, real-world data are becoming increasingly important to decide treatment strategy. This prospective real-world study evaluated the prevalence of EGFR mutations, molecular testing patterns and treatment modalities planned for the management of early-stage NSCLC in LATAM countries of EARLY-EGFR study. The LATAM subset reported a lower prevalence of 39.5% then reported in the overall global (51.0%), Asia (53.0%) and Middle East and Africa (43.8%) cohorts. The reported prevalence is comparatively higher than earlier studies from LATAM countries (22–26%) (15-19). The Brazilian retrospective study in patients with early-stage (IB–IIIA) NSCLC reported a prevalence of 17.3% (20). In another study on 70 patients with early-stage NSCLC from Brazil, the frequency of EGFR mutations was found to be approximately 33% (22). In a retrospective analysis In another retrospective analysis on 513 biopsy samples of patients with NSCLC, EGFR mutations were reported in 22.5% cases (18). In our study, almost 58% of the patients had no smoking history. EGFR mutations have been frequently reported in non-smokers, possibly contributing to higher EGFR mutation rate reported in our study (23,24).

The consensus among most studies is that exon-19 deletions and exon 21 L858R mutations account for majority of EGFR mutations and serve as the most reliable predictors for EGFR-TKIs response (6,25-27). In concordance with the available literature, in our study, exon‑19 deletions and L858R accounted for 60% of the mutations while another 6.7% reported compound mutations with exon-19 deletions and L858R. The remaining 33.3% reported uncommon mutations. The clinical implications of the less common mutations and their response to EGFR-TKIs have not been well understood, but emerging evidence suggests that some patients with these uncommon EGFR mutations may benefit from TKIs or immunotherapies (28).

Real-time PCR was the preferred method, followed by NGS (65.0% and 30.0%). Though NGS panel is recommended mode for mutation testing (6), in line with the global cohort, real-time PCR was preferred in our subset as well. A study in LATAM has also reported using PCR or NGS-based testing mutation analysis; the preference for real-time PCR-based testing may be related to accessibility and cost-effectiveness of the technique (29). Though several clinical guidelines recommend molecular testing for other driver gene mutations, including EGFR, ALK, ROS1, and BRAF in patients with non-squamous NSCLC (6), testing for other mutations was performed in only 23 patients. Most patients (28.8%, 23/80) underwent only ALK testing, of which 2 tested positive. In our study, limited patients underwent MET and KRAS mutation analysis, and no patients reported these mutations. The PD-L1 expression in our study was similar to Brazilian cohort (20).

We found a significantly higher risk of EGFR mutations in patients >60 years of age compared to those aged <60 years and non-smokers compared those with history of smoking, which is in concordance with established data in the literature (19,30-32).

According to the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines^®) for NSCLC, patients with early-stage NSCLC (IB–IIIA) are recommended to receive neo-adjuvant/adjuvant systemic therapy (6). In the LATAM cohort, a significant majority of patients (76.3%) underwent surgery alone. When categorized as per stage, of 44 patients with stage IB–IIIB NSCLC, (neo)AT was planned in 40.9% (n=18) patients. Notably, in 20 patients with stage IIB–IIIB NSCLC, 15 (75.0%) patients were prescribed systemic therapy. These findings highlight an unmet need for better systemic therapy utilization in patients with stage IB–IIB NSCLC. The ADAURA study has established the clinical benefit of osimertinib in patients with early-stage NSCLC (27). In the final overall survival analysis, osimertinib showed significantly improved overall survival (OS) compared to placebo (hazard ratio: 0.49; 95% CI: 0.34–0.70; P<0.001) (33). However, at the time of data collection for our study, osimertinib was not approved in early-stage NSCLC in majority of the LATAM countries; osimertinib therapy was planned in only 2 patients. More than 50% of the patients were not managed through multidisciplinary team approach, emphasizing the need to involve multidisciplinary care for clinical decision-making about (neo)adjuvant therapies after surgical resection, and predicting the treatment response. The paradigm shift from generalized chemotherapy to personalized therapy has made EGFR mutation testing indispensable for managing NSCLC. This information would also be valuable for guiding policymakers in identifying the patients who would benefit maximum from the novel therapies.

The limitations of our study include the inherent limitations associated with real-world studies. Considering the cross-sectional design and short follow-up duration, complete adjuvant treatment data may not have been captured for all patients, thus resulting in incomplete data. Also, as immunotherapy and targeted therapies were not approved in majority of countries in LATAM for early-stage NSCLC, the use of these agents in our study is limited. Also, LATAM is a region with multiple ethnicities and races; small sample size enrolled in our study may not be a true interpretation of the entire region. Thus, studies with larger sample size are required to further validate our findings.

Conclusions

EARLY-EGFR is the first prospective real-world study to report the prevalence of EGFR mutations (approximately 40%) in patients with early-stage NSCLC in LATAM. Our findings emphasize the importance of molecular profiling to identify EGFR mutations as part of initial diagnostic work-up in all patients with early-stage NSCLC. Implementing strategies to increase mutation testing and adoption of multi-disciplinary team structure for optimal systemic treatment in the neo-adjuvant and adjuvant settings are crucial for an effective and patient-centric approach to manage early-stage NSCLC in LATAM.

Acknowledgments

The authors would like to acknowledge Prajakta Nachane (M.Pharm) from Fortrea Scientific Pvt. Ltd. for medical writing support in accordance with GPP2022 guidelines (http://www.ismpp.org/gpp3).

The abstract of this article has been presented in ESMO 2023 (https://www.annalsofoncology.org/article/S0923-7534(23)01593-4/fulltext). Reprint from 1279P Prevalence of EGFR mutations (EGFRm) in patients (pts) with resected stage I–III NSCLC: Results from EARLY-EGFR LATAM Amorin, E. et al. Annals of Oncology, Volume 34, S739, with permission from Elsevier.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-904/rc

Data Sharing Statement: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-904/dss

Peer Review File: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-904/prf

Funding: The study was funded by AstraZeneca International for medical writing, editorial support and publication of this manuscript.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-904/coif). E.A.K. is an investigator at AstraZeneca; and reports speaker honorarium from AstraZeneca, Merck Sharp and Dohme, and Bristol-Myers Squibb. A.P.G. reports provision of study materials by AstraZeneca (to institution). L.F.T.G., N.D., and R.H. are employees at AstraZeneca. L.C. received grants from MSD and Roche and consulting fee, speaker honoraria and travel grants from MSD, AZ, Pfizer and Janssen. The other authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by Comité Institucional de Bioética (CIB) Via Libre ethics committee (Clínica Delgado) [22 June 2021] (No. 6962-2021a). All participating centres were informed and agreed to the study. A signed written informed consent was obtained from the patients during routine clinical care visit.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. The Global Cancer Observatory. Factsheets, Latin America and the Caribbean. [Accessed September 2, 2025]. Available online: https://gco.iarc.who.int/media/globocan/factsheets/populations/904-latin-america-and-the-caribbean-fact-sheet.pdf
2. Raez LE, Santos ES, Rolfo C, et al. Challenges in Facing the Lung Cancer Epidemic and Treating Advanced Disease in Latin America. Clin Lung Cancer 2017;18:e71-9. [Crossref] [PubMed]
3. Yuan M, Huang LL, Chen JH, et al. The emerging treatment landscape of targeted therapy in non-small-cell lung cancer. Sig Transduct Target Ther 2019;4:61. [Crossref] [PubMed]
4. Cagle PT, Allen TC. Lung cancer genotype-based therapy and predictive biomarkers: present and future. Arch Pathol Lab Med 2012;136:1482-91. [Crossref] [PubMed]
5. Lackey A, Donington JS. Surgical management of lung cancer. Semin Intervent Radiol 2013;30:133-40. [Crossref] [PubMed]
6. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer V.1.2024. [Accessed February 07, 2024]. Available online: https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1450
7. Pisters K, Kris MG, Gaspar LE, et al. Adjuvant Systemic Therapy and Adjuvant Radiation Therapy for Stage I-IIIA Completely Resected Non-Small-Cell Lung Cancer: ASCO Guideline Rapid Recommendation Update. J Clin Oncol 2022;40:1127-9. [Crossref] [PubMed]
8. Kratz JR, He J, Van Den Eeden SK, et al. A practical molecular assay to predict survival in resected non-squamous, non-small-cell lung cancer: development and international validation studies. Lancet 2012;379:823-32. [Crossref] [PubMed]
9. O'Leary C, Gasper H, Sahin KB, et al. Epidermal Growth Factor Receptor (EGFR)-Mutated Non-Small-Cell Lung Cancer (NSCLC). Pharmaceuticals (Basel) 2020;13:273. [Crossref] [PubMed]
10. Sequist LV, Yang JC, Yamamoto N, et al. Phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations. J Clin Oncol 2013;31:3327-34. [Crossref] [PubMed]
11. Rosell R, Carcereny E, Gervais R, et al. Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol 2012;13:239-46. [Crossref] [PubMed]
12. Hondelink LM, Ernst SM, Atmodimedjo P, et al. Prevalence, clinical and molecular characteristics of early stage EGFR-mutated lung cancer in a real-life West-European cohort: Implications for adjuvant therapy. Eur J Cancer 2023;181:53-61. [Crossref] [PubMed]
13. Nan X, Xie C, Yu X, et al. EGFR TKI as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer. Oncotarget 2017;8:75712-26. [Crossref] [PubMed]
14. Rosell R, Moran T, Queralt C, et al. Screening for epidermal growth factor receptor mutations in lung cancer. N Engl J Med 2009;361:958-67. [Crossref] [PubMed]
15. Martin C, Cuello M, Barajas O, et al. Real-world evaluation of molecular testing and treatment patterns for EGFR mutations in non-small cell lung cancer in Latin America. Mol Clin Oncol 2022;16:6. [Crossref] [PubMed]
16. Zheng R, Yin Z, Alhatem A, et al. Epidemiologic Features of NSCLC Gene Alterations in Hispanic Patients from Puerto Rico. Cancers (Basel) 2020;12:3492. [Crossref] [PubMed]
17. Freitas HC, Torrezan GT, da Cunha IW, et al. Mutational Portrait of Lung Adenocarcinoma in Brazilian Patients: Past, Present, and Future of Molecular Profiling in the Clinic. Front Oncol 2020;10:1068. [Crossref] [PubMed]
18. Mascarenhas E, Gelatti AC, Araújo LH, et al. Comprehensive genomic profiling of Brazilian non-small cell lung cancer patients (GBOT 0118/LACOG0418). Thorac Cancer 2021;12:580-7. [Crossref] [PubMed]
19. Arrieta O, Cardona AF, Martín C, et al. Updated Frequency of EGFR and KRAS Mutations in NonSmall-Cell Lung Cancer in Latin America: The Latin-American Consortium for the Investigation of Lung Cancer (CLICaP). J Thorac Oncol 2015;10:838-43. [Crossref] [PubMed]
20. Alves Pinto I, de Oliveira Cavagna R, Virginio da Silva AL, et al. EGFR Mutations and PD-L1 Expression in Early-Stage Non-Small Cell Lung Cancer: A Real-World Data From a Single Center in Brazil. Oncologist 2022;27:e899-907. [Crossref] [PubMed]
21. Vandenbroucke JP, von Elm E, Altman DG, et al. Strengthening the Reporting of Observational Studies in Epidemiology (STROBE): explanation and elaboration. PLoS Med 2007;4:e297. [Crossref] [PubMed]
22. Machado-Rugolo J, Baldavira CM, Prieto TG, et al. Clinical outcome of Brazilian patients with non-small cell lung cancer in early stage harboring rare mutations in epidermal growth factor receptor. Braz J Med Biol Res 2023;55:e12409. [Crossref] [PubMed]
23. Grosse C, Soltermann A, Rechsteiner M, et al. Oncogenic driver mutations in Swiss never smoker patients with lung adenocarcinoma and correlation with clinicopathologic characteristics and outcome. PLoS One 2019;14:e0220691. [Crossref] [PubMed]
24. de Alencar VTL, Figueiredo AB, Corassa M, et al. Lung cancer in never smokers: Tumor immunology and challenges for immunotherapy. Front Immunol 2022;13:984349. [Crossref] [PubMed]
25. Shigematsu H, Lin L, Takahashi T, et al. Clinical and biological features associated with epidermal growth factor receptor gene mutations in lung cancers. J Natl Cancer Inst 2005;97:339-46. [Crossref] [PubMed]
26. Hsu WH, Yang JC, Mok TS, et al. Overview of current systemic management of EGFR-mutant NSCLC. Ann Oncol 2018;29:i3-9. [Crossref] [PubMed]
27. Wu YL, Tsuboi M, He J, et al. Osimertinib in Resected EGFR-Mutated Non-Small-Cell Lung Cancer. N Engl J Med 2020;383:1711-23. [Crossref] [PubMed]
28. Zhang T, Wan B, Zhao Y, et al. Treatment of uncommon EGFR mutations in non-small cell lung cancer: new evidence and treatment. Transl Lung Cancer Res 2019;8:302-16. [Crossref] [PubMed]
29. Shen CI, Chiang CL, Shiao TH, et al. Real-world evidence of the intrinsic limitations of PCR-based EGFR mutation assay in non-small cell lung cancer. Sci Rep 2022;12:13566. [Crossref] [PubMed]
30. Nishii T, Yokose T, Miyagi Y, et al. Clinicopathological features and EGFR gene mutation status in elderly patients with resected non-small-cell lung cancer. BMC Cancer 2014;14:610. [Crossref] [PubMed]
31. Choi YH, Lee JK, Kang HJ, et al. Association between age at diagnosis and the presence of EGFR mutations in female patients with resected non-small cell lung cancer. J Thorac Oncol 2010;5:1949-52. [Crossref] [PubMed]
32. Wu Q, Chu M, Hu J, et al. Impact of age on EGFR mutations in never-smoking female lung adenocarcinoma patients with malignant pleural effusion. Int J Clin Exp Pathol 2018;11:2811-5.
33. Herbst RS, Tsuboi M, John T, et al. Overall survival analysis from the ADAURA trial of adjuvant osimertinib in patients with resected EGFR-mutated (EGFRm) stage IB–IIIA non-small cell lung cancer (NSCLC). J Clin Oncol 2023;41:LBA3.