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

Background: exon 20 insertions ( ex20ins) constitute a heterogeneous subset of -activating alterations. However, the effectiveness of standard therapy in patients with ex20ins remains poor.

Methods: In our study, we retrospectively collected next-generation sequencing (NGS) data from 7,831 Chinese NSCLC patients and analyzed the relationship between ex20ins variations and medical records.

Results: Our data showed that ex20ins account for up to 3.5% of all mutation non-small-cell lung cancer (NSCLC) patients and 1.6% of all NSCLC patients in China. Thirty-eight different variants of ex20ins were identified in 129 NSCLC patients. We observed that the patients with ex20ins may benefit from the anti-angiogenesis agents significantly ( = 0.027). In the 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 ex20ins near-loop and tended to have a shorter OS in second-/third-generation EGFR-TKI therapy ( = 0.039). Additionally, median PFS was significantly longer in patients harboring ex20ins far-loop variants who received chemotherapy as a first-line setting ( = 0.037).

Conclusions: Overall survival was significantly longer in ex20ins patients with anti-angiogenesis agents. For the choice of first-line strategy, NSCLC with ex20ins near-loop variants may benefit from second-/third-generation EGFR-TKI, while patients harboring ex20ins far-loop variants might have better outcomes from chemotherapy. could serve as a potential predictive marker in poor prognosis for ex20ins near-loop patients.