AUTHOR=Shi Chao , Xing Ruyue , Li Mengmeng , Feng Junnan , Sun Rui , Wei Bing , Guo Yongjun , Ma Jie , Wang Huijuan 

TITLE=Real-world clinical treatment outcomes in Chinese non-small cell lung cancer with EGFR exon 20 insertion mutations

JOURNAL=Frontiers in Oncology

VOLUME=12

YEAR=2022

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.949304

DOI=10.3389/fonc.2022.949304

ISSN=2234-943X

ABSTRACT=<sec><title>Background</title><p><italic>EGFR</italic> exon 20 insertions (<italic>EGFR</italic> ex20ins) constitute a heterogeneous subset of <italic>EGFR</italic>-activating alterations. However, the effectiveness of standard therapy in patients with <italic>EGFR</italic> ex20ins remains poor.</p></sec><sec><title>Methods</title><p>In our study, we retrospectively collected next-generation sequencing (NGS) data from 7,831 Chinese NSCLC patients and analyzed the relationship between <italic>EGFR</italic> ex20ins variations and medical records.</p></sec><sec><title>Results</title><p>Our data showed that <italic>EGFR</italic> ex20ins account for up to 3.5% of all <italic>EGFR</italic> mutation non-small-cell lung cancer (NSCLC) patients and 1.6% of all NSCLC patients in China. Thirty-eight different variants of <italic>EGFR</italic> ex20ins were identified in 129 NSCLC patients. We observed that the patients with <italic>EGFR</italic> ex20ins may benefit from the anti-angiogenesis agents significantly (<italic>P</italic> = 0.027). In the <italic>EGFR</italic> ex20ins near-loop group, patients who received second-/third-generation EGFR-TKI therapy treatment as first-line treatment had a longer median progression-free survival (PFS) than those who initiated treatment with first-generation EGFR-TKI or chemotherapy. Patients with co-mutations of <italic>EGFR</italic> ex20ins near-loop and <italic>TP53</italic> tended to have a shorter OS in second-/third-generation EGFR-TKI therapy (<italic>P</italic> = 0.039). Additionally, median PFS was significantly longer in patients harboring <italic>EGFR</italic> ex20ins far-loop variants who received chemotherapy as a first-line setting (<italic>P</italic> = 0.037).</p></sec><sec><title>Conclusions</title><p>Overall survival was significantly longer in <italic>EGFR</italic> ex20ins patients with anti-angiogenesis agents. For the choice of first-line strategy, NSCLC with <italic>EGFR</italic> ex20ins near-loop variants may benefit from second-/third-generation EGFR-TKI, while patients harboring <italic>EGFR</italic> ex20ins far-loop variants might have better outcomes from chemotherapy. <italic>TP53</italic> could serve as a potential predictive marker in poor prognosis for <italic>EGFR</italic> ex20ins near-loop patients.</p></sec>