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

Abstract

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

Long-lasting benefit on multimodal treatment combining osimertinib and stereotaxic radiotherapy for metastatic non-small cell lung cancer with the EGFR exon 20 insertion 773-774 HVdelinsLM: a case report

“…Divergent responses on amivantamab were observed, depending on the location of the alteration: helical region (overall response rate (ORR) of 100%), near loop (ORR of 41%), far loop (ORR of 25%). Similar findings were observed with the efficacy of anti-angiogenic therapy dependent on the EGFR ex20ins loop location (24).…”

Predictive Impact of Diffuse Positivity for TTF-1 Expression in Patients Treated With Platinum-Doublet Chemotherapy Plus Immune Checkpoint Inhibitors for Advanced Nonsquamous NSCLC

“… 37 Nevertheless, the EGFR -positive patients in this study had little effect on EGFR TKI, such as EGFR exon20. 38 Therefore, we concluded that EGFR had only positive or little effect on the results of this study.…”

First report of furmonertinib as a first-line treatment in advanced lung adenocarcinoma patients harboring EGFR exon 20 insertion mutations after the kinase domain αC-helix: Two case reports and a literature review

“…[ 8 ] Most EGFR ex20ins mutations are in the loop following the αC-helix of the EGFR kinase domain (M766-C775), and a few occur in the αC-helix (E762-Y764). [ 9 ] Many studies have showed that EGFR ex20ins mutations occurring in the C-terminal loop of the αC-helix can be subdivided into 2 subgroups: near-loop (A767-P772) and far-loop (H773-C775) ex20ins mutations. [ 8 , 9 ] The near-loop region is the region most frequently affected by EGFR ex20ins mutation, and nearly 70% of EGFR ex20ins mutations are in this region.…”

“…[ 9 ] Many studies have showed that EGFR ex20ins mutations occurring in the C-terminal loop of the αC-helix can be subdivided into 2 subgroups: near-loop (A767-P772) and far-loop (H773-C775) ex20ins mutations. [ 8 , 9 ] The near-loop region is the region most frequently affected by EGFR ex20ins mutation, and nearly 70% of EGFR ex20ins mutations are in this region. [ 9 ] Notably, both mutation types (p.S768_D770dupSVD and p.N771_P772insVal) we reported were in the near-loop region.…”

“…[ 8 , 9 ] The near-loop region is the region most frequently affected by EGFR ex20ins mutation, and nearly 70% of EGFR ex20ins mutations are in this region. [ 9 ] Notably, both mutation types (p.S768_D770dupSVD and p.N771_P772insVal) we reported were in the near-loop region.…”