Despite promising data showing that circulating tumour DNA (ctDNA) dynamics during treatment can inform real-time tumour response and recurrence risk1, how best to translate these insights into actionable clinical decision-making remains unclear. Here we report results from the EP-STAR trial—a multi-centre, ctDNA-driven, risk-adapted, non-randomized phase II study (NCT04072107; ClinicalTrials.gov) testing whether a risk-adaptive treatment (RAT) strategy guided by on-treatment ctDNA dynamics can meaningfully improve survival, using nasopharyngeal carcinoma as a model. Eligible patients were enrolled and began treatment with standard-of-care gemcitabine–cisplatin neoadjuvant chemotherapy (GP-NAC; the P in this abbreviation stands for platinum)2, followed by RAT or standard-of-care chemoradiotherapy guided by ctDNA clearance trajectory during GP-NAC. Protocol-eligible patients who did not receive RAT, drawn from a prospectively registered ctDNA biomarker cohort (NCT03855020)3, served as a non-randomized, contemporaneous no-RAT external cohort. The primary end-point was failure-free survival (FFS) in the RAT group. After a median follow-up of 47.3 months, the 3-year FFS was 89.1% (83.2–95.0%) in the RAT group (n = 110). Patients who received RAT showed significantly improved FFS (P = 0.003, log–rank test) compared with the no-RAT external cohort (hazard ratio = 0.41 [0.23–0.75]; P = 0.004, Cox regression model). The RAT strategy was well-tolerated with no treatment-related deaths. Collectively, these data show that a ctDNA-driven RAT paradigm could be a promising strategy to improve survival, challenging the conventional fixed-course, static treatment approach.
尽管已有 promising 数据显示，治疗期间循环肿瘤DNA（ctDNA）的动态变化可实时反映肿瘤缓解情况及复发风险¹，但如何将这些发现转化为可指导临床决策的实际应用仍不清楚。本文报告了EP-STAR试验的结果——这是一项多中心、ctDNA驱动、风险适应性、非随机化的II期研究（NCT04072107；ClinicalTrials.gov），以鼻咽癌为模型，旨在检验基于治疗中ctDNA动态变化指导的风险适应性治疗（RAT）策略能否显著改善生存。符合入组条件的患者在入组后，先接受标准化疗方案——吉西他滨-顺铂新辅助化疗（GP-NAC；缩写中的P代表铂类药物）²，随后根据GP-NAC期间ctDNA清除轨迹，决定接受RAT或标准放化疗。未接受RAT但符合方案入组条件的患者，则从一个前瞻性登记的ctDNA生物标志物队列（NCT03855020）³中筛选，作为非随机化、同期的非RAT外部对照队列。主要研究终点为RAT组的无失败生存期（FFS）。中位随访47.3个月后，RAT组（n=110）的3年FFS率为89.1%（83.2–95.0%）。接受RAT的患者与未接受RAT的外部对照队列相比，FFS显著改善（log-rank检验P=0.003；Cox回归模型风险比=0.41 [0.23–0.75]；P=0.004）。RAT策略的耐受性良好，未发生与治疗相关的死亡。综上，这些数据表明，ctDNA驱动的RAT模式可能是改善患者生存的有效策略，对传统的固定疗程、静态治疗方案提出了挑战。
Risk-adaptive therapy guided by dynamic ctDNA in nasopharyngeal carcinoma
肿瘤(癌症)患者之家