EGFR exon 20 insertion mutations in Chinese advanced non-small cell lung cancer patients: Molecular heterogeneity and treatment outcome from nationwide real-world study. (July 2020)

• Record Type: Journal Article
• Authors: Yang, Guangjian; Li, Jun; Xu, Haiyan; Yang, Yaning; Yang, Lu; Xu, Fei; Xia, Bing; Zhu, Viola W.; Nagasaka, Misako; Yang, Yan; Li, Yapin; Qiu, Weini; Ying, Jianming; Ou, Sai-Hong Ignatius; Wang, Yan
• Is Part Of: Lung cancer. Volume 145(2020)
• Page Start: 186
• Page End: 194
• Publication Date: 2020-07
• Subjects: EGFR epidermal growth factor receptor -- NSCLC non-small cell lung cancer -- ex20ins exon 20 insertion -- TKIs tyrosine kinase inhibitors -- CNS central nervous system -- PFS progression-free survival -- PCR polymerase chain reaction -- NGS next-generation sequencing -- CT computed tomography -- MRI megnetic resonance imaging -- RECIST Response Evaluation Criteria in Solid Tumors -- CR complete response -- PR partial response -- SD stable disease -- PD progressive disease -- ORR objective response rate -- DCR disease control rate -- 95 %CI 95 % confidence interval -- 1st-generation first-generation -- 2nd-generation second-generation -- 4th-line fourth-line; EGFR exon 20 insertion -- Real-world study -- EGFR TKI -- Chinese -- Non-small cell lung cancer; Lungs -- Cancer -- Periodicals; Lung Neoplasms -- Abstracts; Lung Neoplasms -- Periodicals; Poumons -- Cancer -- Périodiques; Lungs -- Cancer; Periodicals; Electronic journals; Electronic journals; 616.99424
• DOI: 10.1016/j.lungcan.2020.03.014
• Languages: English
• ISSNs: 0169-5002

Abstract

Highlights: Largest real-world study of EGFR ex20ins mutations for Chinese NSCLC patients. Thirty-nine subtypes of EGFR ex20ins and treatment outcome were reported. PFS for chemotherapy provided benchmarks for future clinical trials of EGFR ex20ins. Effective therapies against CNS metastasis in EGFR ex20in were urgently needed. Abstract: Objectives: To describe the treatment patterns and outcomes of Chinese non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor ( EGFR ) exon 20 insertion (ex20ins) mutations in real-world as EGFR ex20ins consist of a diverse group of mutations with limited information on the clinical outcome of these patients treated with chemotherapy or EGFR tyrosine kinase inhibitors (TKIs). Materials and methods: Real-world treatment outcomes of Chinese NSCLC patients harboring EGFR ex20ins were retrospectively analyzed based on medical records at different institutions and detailed web-based patient questionnaires. Results: Between March 17, 2018 and December 20, 2018, 165 advanced EGFR ex20ins NSCLC patients treated in 99 hospitals from 26 different regions in China were analyzed. Thirty-nine different molecular variants of EGFR ex20ins were identified with V769_D770insASV being the most common (23.0 %). Central nervous system (CNS) metastasis occurred in 23.0 % of patients at the time of baseline diagnosis. Median progression-free survival (PFS) was significantly longer in patients who received first-line platinum-based chemotherapy (6.4 m; 95 % CI: 5.7–7.1) than all-generation EGFR TKIs (2.9 m; 95 %CI: 1.5–4.3; P < 0.001) or 1st-generation EGFR TKIs (2.0 m; 95 %CI: 0.2–3.8; P < 0.001). Median PFS was numerically longer in patients who received second-line chemotherapy (4.0 m; 95 %CI: 3.2–4.8) than those received second-line EGFR TKIs (2.0 m; 95 %CI: 1.1–2.9; P = 0.342). Patients with CNS metastasis had numerically shorter median PFS than those without CNS metastasis when treated with 1st-line chemotherapy (3.6 m; 95 %CI: 0–8.0 vs. 6.5 m; 95 %CI: 4.9–8.1; P = 0.645) or 1st-line EGFR TKIs (2.0 m; 95 %CI: 0.8–3.2 vs. 2.9 m; 95 %CI: 2.1–3.7; P = 0.058). Conclusion: Chemotherapy is superior to current approved EGFR TKIs as 1st- or 2nd-line treatment of EGFR ex20ins mutations. CNS metastasis conferred numerically shorter PFS with chemotherapy or EGFR TKIs treatment. Targeted agent against EGFR ex20ins with CNS activity is urgently needed.