Utility of ctDNA tumor fraction (TF) as a prognostic biomarker in TALAPRO-3: phase 3 study of talazoparib (TALA) + enzalutamide (ENZA) vs placebo (PBO) + ENZA in patients (pts) with homologous recombination repair (HRR) gene–mutated metasta
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ESMO 2026
2026 年 10 月 23–27 日 · Madrid · 共 2840 条
#CTDNA
2 人 · 2 条 · 8 篇摘要
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ctDNA作为液体活检这一类别,其证据基础已由一系列关键研究奠定:在结直肠癌中,个体化基因方法显示ctDNA能够可靠监测手术与化疗过程中的肿瘤动态[3];CAPP-Seq把检测灵敏度推进到约0.02%的突变等位基因分数,并可比影像更早评估治疗反应[4];TRACERx用系统发生学方法在术后血浆中识别高复发风险的早期肺癌患者[5];综述层面也已把ctDNA的应用归纳为预后判断、疗效与耐药监测以及MRD定量[2][6]。但前列腺是ctDNA释放偏低的瘤种:在640例多癌种患者中,晚期胰腺、卵巢、结直肠等癌种ctDNA检出率超过75%,前列腺癌却不足50%[1],这意味着前列腺场景下的ctDNA分层需要专门验证。
本次#ESMO26现场帖同时涉及两件不同的事。一是TALAPRO-3的ctDNA肿瘤分数(tumor fraction)分析:在HRR缺陷的转移性去势敏感性前列腺癌(mCSPC)中,基线ctDNA阳性(TF ≥1%)在两个治疗组均具rPFS预后价值;第5周时,ctDNA阳性患者在TALA+ENZA组82%实现清除,PBO+ENZA组为68%,且清除与更长的rPFS相关(对比持续ctDNA阳性者HR 0.36)。二是Myriad公布MONSTAR-SCREEN-3新数据,称其基于WGS的Precise MRD™平台在可切除结直肠癌和胰腺癌术后展示出超灵敏MRD检测的潜力。
相对已有认识,这两条各推进一步。TALAPRO-3在含两个随机治疗组的前列腺人群中同时给出两点:塔拉帕利联合恩扎卢胺与安慰剂联合恩扎卢胺之间第5周清除率的差异(82%对68%),以及清除者相对持续阳性者的rPFS差异(HR 0.36),提示早期治疗中ctDNA可能成为风险分层与监测的工具,发帖者明言下一步是验证其能否在PSA之外增加价值。Myriad一侧,术后MRD预测复发的证据此前主要在早期肺癌建立[5],MONSTAR-SCREEN-3则把基于WGS的超灵敏检测推向结直肠癌和胰腺癌的术后场景。
局限同样清楚:上述数字均来自会议期间的社交媒体披露,完整统计细节未披露;TALAPRO-3中HR 0.36来自按ctDNA清除状态分组的比较,其能否直接指导治疗决策、以及在PSA之外的增量价值均待确认;MONSTAR-SCREEN-3目前展示的是检测潜力,能否转化为指导术后治疗决策的临床效用,材料中未给出。
- 1.Detection of circulating tumor DNA in early- and late-stage human malignancies · Sci Transl Med 2014
- 2.Liquid biopsies come of age: towards implementation of circulating tumour DNA · Nat Rev Cancer 2017
- 3.Circulating mutant DNA to assess tumor dynamics · Nat Med 2008
- 4.An ultrasensitive method for quantitating circulating tumor DNA with broad patient coverage · Nat Med 2014
- 5.Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution · Nature 2017
- 6.Integrating liquid biopsies into the management of cancer · Nat Rev Clin Oncol 2017
Plasma ctDNA as standalone or adjunct to tumour tissue for HRR and PI3K/AKT genotyping in mCRPC: PROMPT (NCT04746300)
https://esmocongress.esmo.orgCharacterizing resistance mechanisms and predictors of early progression and long-term response to lorlatinib: Circulating tumor DNA (ctDNA) analyses from the CROWN study
https://esmocongress.esmo.orgClinical utility of reflex liquid comprehensive genomic profiling (LCGP) to complement tumor-informed circulating tumor DNA (ctDNA) monitoring in solid tumors
https://esmocongress.esmo.orgctDNA analysis of the Phase 3 KEYNOTE-B15 trial: neoadjuvant and adjuvant (neoadj-adj) enfortumab vedotin (EV) + pembrolizumab (pembro) for participants (pts) with muscle-invasive bladder cancer (MIBC) who are eligible for cisplatin
https://esmocongress.esmo.orgUltrasensitive monitoring of early ctDNA dynamics during neoadjuvant treatment in early-stage triple-negative breast cancer: Pre-interim results from the B-STRONGER-I study
https://esmocongress.esmo.orgPrognostic impact of postoperative ctDNA surveillance on relapse-free survival and molecular lead time in high-risk breast cancer: JCOG1204A1
https://esmocongress.esmo.orgExtended circulating tumor DNA (ctDNA) sequencing to optimize the selection between anti-EGFR rechallenge and other later lines in patients with RAS/BRAF wild-type metastatic colorectal cancer
https://esmocongress.esmo.orgAlan Tan@alantanmd Myriad Genetics@myriadgenetics