Clinical outcomes in patients with non-small cell lung cancer harboring EGFR Exon20 in-frame insertions in the near-loop and far-loop: Results from LC-SCRUM-Asia

• DOI: 10.1016/j.lungcan.2024.107798
• Publication Date: 2024-04-23T06:59:16Z
• Authors: Masanobu Okahisa; Hibiki Udagawa; Shingo Matsumoto; Terufumi Kato; Hiroshi Yokouchi; Naoki Furuya; Ryota Kanemaru; Ryo Toyozawa; Akihiro Nishiyama; Kadoaki Ohashi; Shingo Miyamoto; Kazumi Nishino; Atsushi Nakamura; Eiji Iwama; Seiji Niho; Hajime Oi; Tetsuya Sakai; Yuji Shibata; Hiroki Izumi; Eri Sugiyama; Kaname Nosaki; Shigeki Umemura; Yoshitaka Zenke; Kiyotaka Yoh; Grace Kah Mun Low; Jianmin Zhuo; Koichi Goto
• Keywords: Male; Adult; Aged, 80 and over; Lung Neoplasms; Aniline Compounds; Exons; Middle Aged; ErbB Receptors; Mutagenesis, Insertional; Treatment Outcome; Carcinoma, Non-Small-Cell Lung; Humans; Female; Protein Kinase Inhibitors; Aged

In this study, we explored the clinical outcomes of non-small cell lung cancer (NSCLC) patients with EGFR Exon20 in-frame insertions (Exon20ins), and the impact of the location of Exon20ins on these clinical outcomes.The efficacies of current systemic therapies in NSCLC patients harboring Exon20ins were investigated using a large-scale clinico-genomic database of LC-SCRUM-Asia, and compared with that of amivantamab in the CHRYSALIS trial.Of the 11,397 patients enrolled in LC-SCRUM-Asia, Exon20ins were detected in 189 patients (1.7 %). Treatment with classical EGFR tyrosine-kinase inhibitors (classical TKIs) was associated with a significantly shorter progression-free survival (PFS) in NSCLC patients with Exon20ins as compared with Exon19 deletions and L858R. Post platinum-based chemotherapy, classical TKIs and immune checkpoint inhibitors (ICIs) were associated with a shorter PFS than with docetaxel in patients with Exon20ins (HR [95 % CI]; TKIs vs docetaxel, 2.16 [1.35-3.46]; ICIs vs docetaxel, 1.49 [1.21-1.84]). Patients treated with amivantamab in the CHRYSALIS trial showed a risk reduction in PFS and overall survival as compared with LC-SCRUM-Asia patients treated with docetaxel, classical TKIs, or ICIs. Among the 189 patients, Exon20ins were classified as near-loop or far-loop insertions in 115 (61 %) and 56 (30 %) patients, respectively. Treatment with osimertinib was associated with a longer PFS in patients with Exon20ins in near-loop as compared with far-loop (median, 5.6 vs. 2.0 months; HR [95 % CI], 0.22 [0.07-0.64]).After platinum-based chemotherapy, classical TKIs and ICIs are less effective in NSCLC patients with Exon20ins, and amivantamab may be a promising targeted therapy. There is a possibility that the location of Exon20ins has an impact on the efficacy of TKIs.