Treatment and Outcomes of Metastatic Non-Small-Cell Lung Cancer Harboring Uncommon <i>EGFR</i> Mutations: Are They Different from Those with Common <i>EGFR</i> Mutations?

• Main Authors: Hyun Ae Jung, Sehhoon Park, Jong-Mu Sun, Se-Hoon Lee, Jin Seok Ahn, Myung-Ju Ahn, Keunchil Park
• Format: Article
• Language: English
• Published: MDPI AG 2020-10-01
• Series: Biology
• Subjects: uncommon <i>EGFR</i> mutation; EGFR-TKIs; T790M; overall survival; progression-free survival
• Online Access: https://www.mdpi.com/2079-7737/9/10/326

Approximately 10% of the epidermal growth factor receptor (<i>EGFR</i>) mutations in non-small-cell lung cancer (NSCLC) are uncommon <i>EGFR</i> mutations. Although the efficacy of second (2G) or third generation (3G) <i>EGFR</i> tyrosine kinase inhibitors (EGFR-TKIs) in the patients with uncommon <i>EGFR</i> mutation has been proven, further studies are warranted to define the optimal treatment approach for uncommon <i>EGFR</i> mutation-positive NSCLC. This study retrospectively investigated the treatment patterns and outcomes of patients with uncommon <i>EGFR</i> mutation-positive NSCLC from January 2011 to December 2019 at the Samsung Medical Center, Seoul, Korea. During the study, 2121 patients with <i>EGFR</i> mutation-positive NSCLC received first-generation (1G, gefitinib or erlotinib) or 2G EGFR-TKI (afatinib) as the first-line (1L) systemic therapy. Of this, 135 (6.4%) patients harbored uncommon <i>EGFR</i> mutations. Of 135, 54 (40%, 54/135) patients had overlapping mutations with major <i>EGFR</i> mutations. The objective response rate (ORR) for the 1L EGFR-TKI was 63.3%. The median progression-free survivals (PFSs) were 8.6 months (95% CI: 3.8–13.5), 11.7 months (95% CI: 6.6–16.7), 7.7 months (95% CI: 4.9–17.4), and 5.0 months (95% CI: 3.7–6.1) for major uncommon <i>EGFR</i> mutation (G719X, L861Q), compound mutation with major <i>EGFR</i> mutation (Del 19 or <i>EGFR</i> exon 21 p.L858R), other compound mutation, and other uncommon mutations, respectively. The median overall survivals (OSs) were 25.6 months (16.9–34.2), 28.8 (95% CI: 24.4–33.4), 13.5 months (95% CI: 7.4–27.8), and 9.4 months (95% CI: 3.4–10.5) for major uncommon <i>EGFR</i> mutation (G719X), compound mutation with major <i>EGFR</i> mutation (Del 19 or <i>EGFR</i> exon 21 p.L858R), other compound mutation, and other uncommon mutations, respectively. The response rate, median PFS, and OS were 63.3%, 16.3 months (95% CI: 15.6–16.9), and 37.5 months (95% CI: 35.4–39.6) for common <i>EGFR</i> mutation-positive NSCLC. After failing 1L <i>EGFR</i>-TKI, repeated tissue or liquid biopsy were carried out on 44.9% (35/78) of patients with T790M detected in 10/35 (28.6%) patients. With subsequent 3G <i>EGFR</i>-TKI after failing the first-line <i>EGFR</i>-TKI, the ORR and PFS for 3G <i>EGFR</i>-TKI were 80% and 8.9 months (95% CI: 8.0–9.8). These patients showed a median OS of 34.6 months (95% CI: 29.8–39.4). The ORR, PFS and OS were poorer in patients with uncommon (especially other compound and other uncommon mutation) than those with common <i>EGFR</i> mutations. T790M was detected in 28.6% of the uncommon <i>EGFR</i> mutation-positive patients for whom prior 1G/2G <i>EGFR</i>-TKIs failed and underwent repeat biopsy at the time of progression.