SCI

9 July 2024

Mutational characteristics and clinical outcomes for lung adenocarcinoma with EGFR germline mutations

(Journal of Thoracic Oncology, IF: 21.0)

  • Kelsey Pan, Jennifer Owens, Yasir Elamin, Charles Lu, Mark Routbort, Jianjun Zhang, Frank Fossella, Marcelo V. Negrao, Mehmet Altan, Jenny Pozadzides, Ferdinandos Skoulidis, Anne Tsao, Tina Cascone, John V. Heymach, Edwin Ostrin, Xiuning Le

  • CORRESPONDENCE TO: xle1@mdanderson.org

Background 背景

Germline mutations driving lung cancer have been infrequently reported in literature, with EGFR T790M being a known germline mutation identified in 1% of NSCLC. Typically, a somatic EGFR mutation is acquired to develop lung adenocarcinoma. Osimertinib has become standard-of-care treatment for EGFR T790M-positive lung cancer.

文献中通常很少报道导致癌症的种系突变，EGFR T790M是在1%的NSCLC中发现的已知种系突变。通常，体细胞EGFR突变会发展为肺腺癌。奥希替尼已成为EGFR T790M阳性肺癌的标准治疗方法。

 

Methods 方法

We perform a retrospective analysis through the Lung Cancer Moon Shot GEMINI database at the UT MD Anderson Cancer Center. Of the patients that underwent cfDNA analysis, germline mutations were identified by those with high variant allelic fraction (VAF) approximating 50%, followed by further confirmation on genetic testing.

我们通过UT MD Anderson癌症中心的肺癌Moon Shot GEMINI数据库进行回顾性分析。在接受cfDNA分析的患者中，由高变异等位基因占比（VAF）接近50%的患者鉴定种系突变，随后在基因测试中得到进一步确认。

 

Results 结果

We identified 22 patients with germline EGFR mutations, with the majority harboring an EGFR T790M mutation (95.5%) and EGFR L858R somatic mutation (50%). Notably, most patients were female (86.4%), non-smokers (81.8%), Caucasian (86.4%), have family history of lung cancer (59.1%), and stage IV at diagnosis (72.7%). A distinct radiographic pattern of small multifocal ground-glass pulmonary nodules was observed in the majority of our cohort (72.7%). Among the 18 with advanced-stage NSCLC, 12 (66.7%) were treated with first-line osimertinib, demonstrating a median PFS of 16.9 months (95% CI; 6.3-NR). Others were treated with first line afatinib (11.1%) or chemotherapy (22.2%). Among the 17 patients treated with osimertinib (in first or second-line), mPFS was 20.4 months (95% CI; 6.3-NR) and mOS was 82.0 months (95% CI; 28.4-NR).

我们鉴定了22例种系EGFR突变患者，其中大多数患者携带EGFR T790M突变（95.5%）和EGFR L858R体细胞突变（50%）。值得注意的是，大多数患者是女性（86.4%）、非吸烟者（81.8%）、高加索人（864%）、有癌症家族史（59.1%）并且诊断时为IV期（72.7%）。在我们的大多数队列中（72.7%）观察到了明显的多灶磨玻璃样小肺结节的放射学模式。在18例晚期NSCLC患者中，12例（66.7%）接受了一线奥西替尼治疗，中位PFS为16.9个月（95%CI；6.3-NR）。其他患者接受一线阿法替尼治疗（11.1%）或化疗（22.2%）。在17名接受奥西替尼治疗的患者中（一线或二线），mPFS为20.4个月（95%CI；6.3-NR），mOS为82.0个月（95%CI；28.4-NR）。

 

Conclusion 结论

Based on our institutional cohort, NSCLC driven by EGFR germline mutations occur more frequently in non-smoking, Caucasian females with multi-focal pulmonary nodules radiographically. Osimertinib for advanced germline EGFR-mutated NSCLC renders similar PFS compared to somatic T790M EGFR-mutated NSCLC.

根据我们机构的队列，由EGFR种系突变驱动的NSCLC在放射学上更频繁地发生在具有多灶性肺结节的不吸烟的高加索女性中。与体细胞T790M EGFR突变的NSCLC相比，奥西替尼治疗晚期种系EGFR突变NSCLC具有相似的PFS。