This multicenter retrospective study compared progression-free survival (PFS) and overall survival (OS) among EGFR exon 19 deletion subtypes in 111 patients with advanced NSCLC treated predominantly with first-line osimertinib (86.5%), and used whole-exome sequencing from AACR GENIE and MSK datasets to characterize co-occurring genomic alterations.
Non-E746_A750del subtypes (n=25) had shorter median PFS vs. E746_A750del (n=86): 14.3 vs. 20.6 months (p<0.05). The L747_A750delinsP subtype (n=4) showed the worst outcomes — median PFS 3.5 vs. 20.6 months and median OS 11.8 vs. 48.5 months compared to E746_A750del (both p<0.001) — and was genomically characterized by frequent CDKN2A/B homozygous deletions and MYC amplifications.
- The L747_A750delinsP subgroup is very small (n=4), limiting statistical reliability and generalizability. - Retrospective, multicenter design introduces potential selection and ascertainment biases. - Genomic co-alteration analyses relied on external public databases rather than the clinical cohort itself.
Clinicians should be aware that non-E746_A750del EGFR exon 19 deletions — especially L747_A750delinsP — may signal a high-risk group with markedly worse outcomes on osimertinib. Consider closer monitoring and early investigation of resistant mechanisms or clinical trial enrollment for patients harboring these uncommon subtypes.
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