Mapendano C K, Nøhr A K, Sønderkær M, Pagh A, Carus A, Lörincz T, Haslund C A, Poulsen L Ø, Ernst A, Bødker J S, Dahl S C, Sunde L, Brügmann A H, Vesteghem C, Pedersen I S, Ladekarl M
Department of Oncology and Clinical Cancer Research Center, Aalborg University Hospital, Aalborg, Denmark.
Center for Clinical Data Science, Aalborg University and Aalborg University Hospital, Aalborg, Denmark.
ESMO Open. 2025 Jan;10(1):104089. doi: 10.1016/j.esmoop.2024.104089. Epub 2025 Jan 3.
In a per-protocol analysis of molecularly profiled patients with treatment-refractory, end-stage cancer discussed at the National Molecular Tumor Board (NMTB), we aimed to assess the overall survival (OS) outcome of targeted treatment compared with no targeted treatment.
Patients were prospectively included at a single oncological center. Whole exome and RNA sequencing (tumor-normal) were carried out, and cases were presented at the NMTB for discussion of targeted treatment. Treatment was available through a basket trial, by compassionate use or in early clinical trials.
One hundred and ninety-six patients were included from 2020 to 2023. In all but three patients a driver variant was disclosed, while 42% had simultaneous affection of more than three oncogenic pathways. In 42% of patients a druggable target was identified but two-thirds did not receive the suggested treatment. The fraction of patients initiating treatment yearly rose from 8% to 22%. For patients treated (N = 30), the clinical benefit rate was 44% and median time on treatment was 3.5 months. Druggable targets were enriched in lung cancers, while patients receiving or not receiving targeted treatment had similar clinical characteristics. The median OS was longer for patients receiving targeted treatment (15 months), but similar for patients with no druggable target and suggested targeted treatment not initiated (5 and 6 months, respectively) (P = 0.004). In multivariate analysis, targeted treatment (hazard ratio 0.43, confidence interval 0.25-0.72), few metastatic sites, and adenocarcinoma histology were predictive of improved OS while alterations of the RTK/RAS pathway were prognostically unfavorable.
Tissue-agnostic targeted treatment based on molecular tumor profiling is possible in an increasing fraction of end-stage cancer patients. In those who receive targeted treatment, results strongly suggest a significant survival benefit.
在国家分子肿瘤委员会（NMTB）讨论的针对分子特征分析的难治性晚期癌症患者的符合方案分析中，我们旨在评估靶向治疗与非靶向治疗相比的总生存期（OS）结果。
患者在单一肿瘤中心前瞻性纳入。进行了全外显子组和RNA测序（肿瘤-正常对照），病例提交至NMTB讨论靶向治疗。治疗可通过篮子试验、同情用药或早期临床试验获得。
2020年至2023年共纳入196例患者。除3例患者外，其余均发现驱动变异，42%的患者同时涉及超过三条致癌途径。42%的患者鉴定出可靶向治疗的靶点，但三分之二的患者未接受建议的治疗。每年开始治疗的患者比例从8%升至22%。接受治疗的患者（N = 30）临床获益率为44%，中位治疗时间为3.5个月。可靶向治疗的靶点在肺癌中富集，接受或未接受靶向治疗的患者具有相似的临床特征。接受靶向治疗的患者中位OS更长（15个月），但未发现可靶向治疗靶点且未开始建议的靶向治疗的患者中位OS相似（分别为5个月和6个月）（P = 0.004）。多因素分析中，靶向治疗（风险比0.43，置信区间0.25 - 0.72）、转移部位少和腺癌组织学是OS改善的预测因素，而RTK/RAS途径改变预后不良。
基于分子肿瘤分析的组织非特异性靶向治疗在越来越多的晚期癌症患者中是可行的。在接受靶向治疗的患者中，结果强烈提示有显著的生存获益。
