Feng Xiangran, Zeng Ran, Lyu Mengchen, Chen Xiaoyan, Xu Ziwei, Hu Yue, Bao Zhiyao, Sun Xianwen, Zhao Jingya, Zhou Ling, Zhou Jun, Gao Beili, Dong Lei, Xiang Yi
Department of Respiratory and Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Department of Pathology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Front Oncol. 2025 Apr 2;15:1514653. doi: 10.3389/fonc.2025.1514653. eCollection 2025.
The differences in clinical characteristics and treatment prognosis in NSCLC patients harboring primary and acquired mutations are still poorly understood.
From Oct 2017 to Dec 2023, 10, 211 lung cancer patients at Shanghai Ruijin Hospital were reviewed. 88 primary and 15 acquired -mutated NSCLC patients resistant to TKIs were included in the study.
Primary -mutated patients preferentially occurred in the elderly (median age: 67 vs 61, p=0.015), males (53.4% vs 26.7%, p=0.056), former/current smokers (36.5% vs 6.7%, p=0.033), non-adenocarcinoma (11.4% vs 0%, P=0.351) compared to acquired -mutated patients. Significant differences in gender (33.3% vs 62.3%, p=0.012), smoking history (22.2% vs 43.1%, p=0.063), and adenocarcinomas (100% vs 83.6%, p=0.028) were observed between primary / co-mutated and non-co-mutated groups. While primary and acquired / co-mutated patients had similar clinical characteristics, with mutations being the most common coexisting oncogene (30.7% and 93.3%). The genotype of mutations differed, with acquired -mutated cases showing more complexity and a higher rate of dual mutations (35.7%) compared to primary cases. For primary / co-mutated patients, no matter what kinds of therapies, the 19del patients had a better prognosis than non-19del patients, and the first line mPFS was NR and 9.0 months (95% CI: 7.7-10.3 months) (p=0.0062), respectively. Dabrafenib and trametinib plus 3rd TKIs improved the prognosis of primary / non-19del co-mutated patients, achieving ORR and mPFS of 100% (3/3) and 12 months. For acquired co-mutated patients, the mPFS for 5 patients was 8.6 months (95% CI: 5.4-11.8 months). No new safety concerns and > grade 3 AEs were noted.
Together, our study demonstrates that primary and acquired -mutant patients show distinct differences in some clinical and molecular characteristics, but acquired / co-mutated and primary / non-19del co-mutated patients may both respond to triple-targeted therapy.
对于携带原发性和获得性突变的非小细胞肺癌（NSCLC）患者，其临床特征和治疗预后的差异仍知之甚少。
回顾性分析2017年10月至2023年12月在上海瑞金医院就诊的10211例肺癌患者。本研究纳入了88例对酪氨酸激酶抑制剂（TKIs）耐药的原发性突变和15例获得性突变的NSCLC患者。
与获得性突变患者相比，原发性突变患者更常见于老年人（中位年龄：67岁 vs 61岁，p = 0.015）、男性（53.4% vs 26.7%，p = 0.056）、既往/当前吸烟者（36.5% vs 6.7%，p = 0.033）、非腺癌患者（11.4% vs 0%，P = 0.351）。在原发性/共突变组和非共突变组之间观察到性别（33.3% vs 62.3%，p = 0.012）、吸烟史（22.2% vs 43.1%，p = 0.063）和腺癌（100% vs 83.6%，p = 0.028）存在显著差异。虽然原发性和获得性/共突变患者具有相似的临床特征，其中突变是最常见的共存致癌基因（30.7%和93.3%）。突变的基因型有所不同，与原发性病例相比，获得性突变病例表现出更高的复杂性和更高的双突变率（35.7%）。对于原发性/共突变患者，无论采用何种治疗方法,19号外显子缺失（19del）患者的预后均优于非19del患者，一线中位无进展生存期（mPFS）分别为未达到（NR）和9.0个月（95%CI：7.7 - 10.3个月）（p = 0.0062）。达拉非尼和曲美替尼联合第三代TKIs改善了原发性/非19del共突变患者的预后，客观缓解率（ORR）和mPFS分别达到100%（3/3）和12个月。对于获得性共突变患者，5例患者的mPFS为8.6个月（95%CI：5.4 - 11.8个月）。未发现新的安全性问题和>3级不良事件（AEs）。
总之，我们的研究表明，原发性和获得性突变患者在一些临床和分子特征上存在明显差异，但获得性/共突变和原发性/非19del共突变患者可能都对三联靶向治疗有反应。
