Efficacy of Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitors in Metastatic Non-Small Cell Lung Cancer Patients with Poor Performance Status and Epidermal Growth Factor Receptor Mutations: Findings from the Japanese Cancer Database

A nationwide prospective registry study, encompassing 9872 patients with local or advanced non-small cell lung cancer, was conducted to determine the benefit of harboring epidermal growth factor receptor (EGFR)tyrosine kinase inhibitors (TKIs) in this population and identify relevant prognostic factors. Outcomes were compared between poor- and good-performance status (PS) patients treated with EGFR-mutated lung cancer therapies. We demonstrated that poor PS at diagnosis was rare, EGFR-TKIs had limited efficacy in poor-PS patients, and liver metastasis and hypoalbuminemia may reduce EGFR-TKI efficacy in these patients. Background: In advanced non-small cell lung cancer (NSCLC) patients harboring epidermal growth factor receptor (EGFR) mutations, those with impaired performance status (PS) treated with EGFR-tyrosine kinase inhibitors (TKIs) have demonstrated comparable activities to good-PS patients. Due to the limited sample size and inclusion of older adult patients with good PS, these findings may not accurately depict the efficacy of EGFR-TKI in poor-PS patients. We investigated the benefit of EGFR-TKIs in this population and identified relevant prognostic factors. Patients and Methods: This nationwide prospective registry study included 9872 patients with local or advanced NSCLC. Outcomes were compared between poor- and good-PS patients treated with EGFR-mutated lung cancer therapies. Results: Of 9872 NSCLC patients, 1965 (19.9%) had EGFR mutations, with 1846 (93.9%) presenting common EGFR mutations. Poor PS (PS score >= 3) was noted in 171 patients (8.7%) and identified as an independent prognostic factor; those with poor PS had a significantly lower 1-year survival rate. The median overall survival (OS) for EGFR-TKI-treated good PS patients was 31.5 (95% confidence interval, 29.6-33.4) months. Among poor -PS patients with EGFR mutations, 135 (78.9%) of whom were treated with EGFR-TKI had an OS of 15.5 (12.7-18.3) months, while those receiving only supportive care had an OS of 2.5 (1.4-3.6) months ( P < . 001). Hypoalbuminemia ( < 3.5 g/dL), liver metastasis, and uncommon EGFR mutations were associated with poor prognosis. Conclusion: Poor PS at diagnosis was rare and associated with limited EGFR-TKI efficacy and a dismal prognosis. Liver metastasis and hypoalbuminemia may reduce EGFR-TKI efficacy in these patients.