Chemotherapy outcomes in EGFR‐TKI resistant patients with common and uncommon EGFR mutation: An exploratory retrospective cohort study

• Published in: Thoracic cancer 2023-07, Vol.14 (19), p.1857-1864
• Main Authors: Lin, Chien‐Yu, Hu, Chia‐Hao, Hsu, Chia‐Fu, Tsai, Jeng‐Shiuan, Chen, Chian‐Wei, Lin, Chia‐Yin, Chang, Chao‐Chun, Yen, Yi‐Ting, Tseng, Yau‐Lin, Su, Po‐Lan, Lin, Chien‐Chung
• Format: Article
• Language: English
• Subjects: Age; Cancer; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - genetics; Chemotherapy; Cohort analysis; Enrollments; epidermal growth factor receptor; ErbB Receptors; Expected values; Humans; Liver; Lung Neoplasms - drug therapy; Lung Neoplasms - genetics; Lymphatic system; Medical prognosis; Metastasis; Mutation; Original; Patients; Prospective Studies; Protein Kinase Inhibitors - therapeutic use; Regression analysis; Retrospective Studies; Software; tyrosine kinase inhibitors; uncommon mutation
• ISSN: 1759-7706; 1759-7714
• DOI: 10.1111/1759-7714.14930

Background Some prospective studies have shown that second‐generation tyrosine kinase inhibitors (TKIs) provide better control in patients with non‐small cell lung cancer (NSCLC) with uncommon epidermal growth factor receptor (EGFR) mutations. However, studies comparing second‐line chemotherapy efficacy between NSCLC patients with common and uncommon EGFR mutations remain rare. This retrospective study compared treatment outcomes in these patients. Methods Patients with EGFR‐mutated advanced‐stage NSCLC who received first‐line EGFR‐TKIs in a tertiary referral center were retrospectively reviewed between January 2010 and August 2022. Patients with a negative T790M test at disease progression who received second‐line chemotherapy were enrolled. We compared progression‐free (PFS) and overall (OS) survival between advanced NSCLC patients with common and uncommon EGFR mutations using Kaplan–Meier and log‐rank tests. Results In total, 209 (54.8%) patients had a negative T790M mutation test and received second‐line chemotherapy, of which 192 (91.8%) had a common EGFR mutation (exon 19 deletion or exon 21 L858R substitution), and 17 (8.2%) had an uncommon EGFR mutation. Patients with common EGFR mutations had significantly longer PFS than those with uncommon EGFR mutations (4.57 vs. 2.57 months, p = 0.031). A Cox proportional hazard regression analysis controlling for potential confounding factors indicated that an uncommon EGFR mutation was an independent prognostic factor for PFS. Conclusion This study suggests that patients with uncommon EGFR mutations have poorer chemotherapy responses and shorter survival than those with common EGFR mutations. The development of new treatment strategies for these patients remains an unmet need. The comparison of second‐line chemotherapy efficacy between patients with common and uncommon EGFR mutations had not been previously investigated. Our study demonstrates that patients with uncommon EGFR mutations experience a shorter progression‐free survival compared with those with common mutations (4.57 vs. 2.57 months, p = 0.031). The uncommon EGFR mutation is also an independent poor prognostic factor based on COX proportional hazard regression analysis.