Lung cancer (Amsterdam, Netherlands) · 2026
Clinical outcomes and genomic features of uncommon EGFR exon 19 deletion subtypes in osimertinib-treated non-small cell lung cancer.
СтатьяМногоцентровое исследованиеНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Hatano Hiroto, Yoshida Tatsuya, Higashiyama Ryoko Inaba, Shirasawa Masayuki, Nakahara Yoshiro, Naoki Katsuhiko, Nokihara Hiroshi, Gosho Kentaro, Uehara Yuji, Hosomi Yukio, Kiritani Ayu, Wakui Hiroshi, Shinno Yuki, Okuma Yusuke, Horinouchi Hidehito, Yamamoto Noboru, Goto Yasushi
Аннотация
BACKGROUND: Epidermal growth factor receptor (EGFR) exon 19 deletion subtypes may be associated with differential survival outcomes following EGFR-tyrosine kinase inhibitor treatment. However, evidence remains scarce, particularly regarding osimertinib, and the underlying biological mechanisms are poorly understood. We aimed to compare survival outcomes among EGFR exon 19 deletion subtypes in patients with non-small cell lung cancer (NSCLC) treated with osimertinib.
METHODS: In this multicenter retrospective study, patients with NSCLC were stratified according to exon 19 deletion subtypes. Whole-exome sequencing data from the American Association for Cancer Research Genomics Evidence Neoplasia Information Exchange registry and Memorial Sloan Kettering Clinicogenomic Harmonized Oncologic Real-World Dataset were analyzed to investigate co-occurring genomic alterations.
RESULTS: Overall, 111 patients with advanced EGFR exon 19 deletion-positive NSCLC were analyzed and 86.5% received osimertinib as first-line therapy. Patients with non-E746_A750del (n = 25) had shorter progression-free survival (PFS) than those with E746_A750del (n = 86) (median: 14.3 vs. 20.6 months; p < 0.05). Among non-E746_A750del subtypes, L747_A750delinsP (n = 4) had a particularly poor prognosis, with significantly worse survival than those with E746_A750del (median PFS: 3.5 vs. 20.6 months; p < 0.001, and median overall survival: 11.8 vs. 48.5 months; p < 0.001). In public database analyses, non-E746_A750del had a higher rate of RBM10 co-mutations, whereas L747_A750delinsP was characterized by frequent CDKN2A/B homozygous deletions and MYC amplifications.
CONCLUSIONS: Non-E746_A750del was associated with poorer outcomes, with L747_A750delinsP potentially being a high-risk subtype. Differences in co-occurring genomic alterations may contribute to the prognostic heterogeneity among exon 19 deletion subtypes.
METHODS: In this multicenter retrospective study, patients with NSCLC were stratified according to exon 19 deletion subtypes. Whole-exome sequencing data from the American Association for Cancer Research Genomics Evidence Neoplasia Information Exchange registry and Memorial Sloan Kettering Clinicogenomic Harmonized Oncologic Real-World Dataset were analyzed to investigate co-occurring genomic alterations.
RESULTS: Overall, 111 patients with advanced EGFR exon 19 deletion-positive NSCLC were analyzed and 86.5% received osimertinib as first-line therapy. Patients with non-E746_A750del (n = 25) had shorter progression-free survival (PFS) than those with E746_A750del (n = 86) (median: 14.3 vs. 20.6 months; p < 0.05). Among non-E746_A750del subtypes, L747_A750delinsP (n = 4) had a particularly poor prognosis, with significantly worse survival than those with E746_A750del (median PFS: 3.5 vs. 20.6 months; p < 0.001, and median overall survival: 11.8 vs. 48.5 months; p < 0.001). In public database analyses, non-E746_A750del had a higher rate of RBM10 co-mutations, whereas L747_A750delinsP was characterized by frequent CDKN2A/B homozygous deletions and MYC amplifications.
CONCLUSIONS: Non-E746_A750del was associated with poorer outcomes, with L747_A750delinsP potentially being a high-risk subtype. Differences in co-occurring genomic alterations may contribute to the prognostic heterogeneity among exon 19 deletion subtypes.