Efficacy and Safety of EGFR-TKIs for Elderly Patients With NSCLC

In a new study, researchers investigated the effectiveness and safety of EGFR-tyrosine kinase inhibitors in elderly patients with EGFR-mutated advanced non-small-cell lung cancer (NSCLC).

Lung cancer is a significant global health issue, being the second most commonly diagnosed cancer and the leading cause of cancer-related death worldwide. Non-small-cell lung cancer (NSCLC) represents the majority of lung cancer cases and is often diagnosed at an advanced stage. Epidermal growth factor receptor (EGFR) mutations are more common in Asian NSCLC populations than in Western populations. 

Activating EGFR mutations, such as exon 19 deletions and L858R, are predictive of response to tyrosine kinase inhibitors (TKIs) and have revolutionized the treatment landscape for patients with EGFR-mutated NSCLC. However, most clinical trials tend to lack data for the elderly population, even though a significant proportion of lung cancer patients are aged 65 years and older. This underrepresentation of elderly patients in clinical trials limits our understanding of the effectiveness and safety of EGFR-TKIs in this specific population.

In this new study, researchers Ling-Jen Hung, Ping-Chih Hsu, Cheng-Ta Yang, Chih-Hsi Scott Kuo, John Wen-Cheng Chang, Chen-Yang Huang, Ching-Fu Chang, and Chiao-En Wu from Chang Gung University and Taoyuan General Hospital conducted a multi-institute retrospective study to investigate the effectiveness and safety of afatinib, gefitinib, and erlotinib for treatment-naïve elderly patients with EGFR-mutated advanced NSCLC. On January 8, 2024, their research paper was published in Aging’s Volume 16, Issue 1, entitled, “Effectiveness and safety of afatinib, gefitinib, and erlotinib for treatment-naïve elderly patients with epidermal growth factor receptor-mutated advanced non-small-cell lung cancer: a multi-institute retrospective study.”

“[…] comparisons of the effectiveness and safety of these EGFR-TKIs approved for patients aged ≥65 years are limited. The available real-world evidence for EGFR-TKI treatment of elderly patients is also limited. Therefore, this study aimed to describe the effectiveness and safety of afatinib, gefitinib, and erlotinib for treatment-naïve elderly patients (aged ≥65 years) with EGFR-mutated advanced NSCLC.”

The Study

In this study, 1,343 treatment-naïve patients with EGFR-mutated advanced NSCLC were enrolled from multiple hospitals in Taiwan. The patients were divided into four age groups: <65 years, 65-74 years, 75-84 years, and ≥85 years. Patient characteristics, including sex, smoking history, performance status, tumor involvement, EGFR mutation type, metastatic sites, and choice of EGFR-TKI, were compared among the age groups.

The researchers found that afatinib was more effective than gefitinib and erlotinib in elderly patients aged ≥65 years, as evidenced by longer median progression-free survival (PFS) and overall survival (OS). The median PFS for afatinib was 14.7 months, compared to 9.9 months for gefitinib and 10.8 months for erlotinib (p = 0.003). Similarly, the median OS for afatinib was 22.2 months, compared to 17.7 months for gefitinib and 18.5 months for erlotinib (p = 0.026).

Further analysis by age subgroup revealed that the significant differences in PFS and OS were primarily driven by patients aged 65-74 years. In this age group, afatinib demonstrated superior efficacy compared to gefitinib and erlotinib, with a median PFS of 14.7 months and median OS of 22.2 months (p = 0.032 for PFS, p = 0.018 for OS). While afatinib showed greater effectiveness, it was also associated with more adverse events (AEs) compared to gefitinib and erlotinib. The study reported a higher incidence of grade ≥3 AEs, including skin toxicities, paronychia, mucositis, and diarrhea, in patients receiving afatinib. Notably, patients receiving afatinib also required more dose reductions or discontinuation due to AEs.

Various factors were identified as independent prognostic factors of PFS and OS in elderly patients with EGFR-mutated advanced NSCLC. A performance status score of 2-4, stage IV disease, liver, bone, pleural, adrenal, and pericardial metastasis, and treatment with gefitinib were associated with worse PFS and OS.


This large retrospective study provides valuable real-world evidence on the effectiveness and safety of EGFR-TKIs in elderly patients with EGFR-mutated advanced NSCLC. The findings suggest that afatinib is more effective as a first-line treatment than gefitinib or erlotinib for elderly patients, particularly those aged 65-74 years. However, it is important to consider the increased risk of adverse events associated with afatinib in this population. These results highlight the need for individualized treatment decisions for elderly patients with NSCLC. Clinicians should carefully consider the patient’s age, performance status, and comorbidities when selecting an appropriate EGFR-TKI. Additionally, close monitoring of AEs and appropriate management strategies are crucial to ensure optimal treatment outcomes in this population.

“In conclusion, this study demonstrated the effectiveness and safety of EGFR-TKIs for elderly patients with EGFR-mutated advanced NSCLC, a population that has often been underrepresented in clinical trials and real-world evidence. For elderly patients with EGFR-mutated advanced NSCLC, clinicians were more likely to prefer gefitinib or erlotinib to afatinib as a therapy, in contrast to the treatment regimen for younger patients. Nevertheless, afatinib still emerged as the primary choice for first-line treatment for older patients compared to other EGFR-TKIs, as it is more effective than gefitinib or erlotinib in elderly patients with EGFR-mutated advanced NSCLC.”

Click here to read the full research paper published in Aging.

Aging is an open-access, traditional, peer-reviewed journal that has published high-impact papers in all fields of aging research since 2009. All papers are available to readers (at no cost and free of subscription barriers) in bi-monthly issues at Aging-US.com.

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