维持治疗可改善一线化疗后缓解的转移性鼻咽癌患者的生存结局：一项多中心、随机对照临床研究。
Maintenance therapy improves the survival outcomes of patients with metastatic nasopharyngeal carcinoma responding to first-line chemotherapy: a multicentre, randomized controlled clinical study.
机构信息
Department of Oncology, The Fourth Affiliated Hospital of Guangxi Medical University, No.1 Liushi Road, Liuzhou, 545000, Guangxi, China.
Department of Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530000, China.
出版信息
J Cancer Res Clin Oncol. 2023 Jul;149(8):4327-4338. doi: 10.1007/s00432-022-04341-2. Epub 2022 Sep 8.
PURPOSE
To explore the safety and role of tegafur/gimeracil/oteracil (S1) maintenance therapy (MT) in metastatic nasopharyngeal carcinoma (NPC) patients after response to first-line chemotherapy and to assess outcome-associated biomarkers.
METHODS
This was a multicentre, open-label, randomized controlled study involving metastatic NPC patients recruited (from May 2015 to May 2019) at five hospitals in China. The participants were randomized to S1-MT (receiving S1 MT until disease progression or intolerance) or non-MT (followed up until disease progression) groups. The primary endpoint was the progression-free survival (PFS). The secondary endpoints were the overall survival (OS), the correlation between EBV-DNA, serum amyloid A (SAA) status, and outcomes after the first-line chemotherapy, and safety.
RESULTS
The median follow-up was 24.3 months; 88 and 95 participants were evaluable in the S1-MT and non-MT groups, respectively. Compared with non-MT, S1-MT prolonged PFS (16.9 vs. 9.3 months, P < 0.001) and OS (33.6 vs. 20.6 months, P < 0.001). Regardless of their EBV-DNA status after first-line chemotherapy, participants were able to benefit from S1 MT, but EBV-DNA-positive participants benefited more significantly (PFS: HR = 0.600, 95% CI = 0.373-0.965, P = 0.035; OS: HR = 0.393, 95% CI = 0.227-0.681, P = 0.001). MT only improved PFS and OS in patients with an SAA decline after first-line chemotherapy (PFS: HR = 0.570, 95% CI = 0.350-0.919, P = 0.021; OS: HR = 0.404, 95% CI = 0.230-0.709, P = 0.002). The median S1 treatment was 23 cycles. Grade 1-2 skin pigmentation, oral mucositis, and hand and foot syndrome were the main adverse reactions.
CONCLUSION
For metastatic NPC patients with first-line chemotherapy response, S1 MT can improve PFS and OS, with good tolerability. EBV-DNA and SAA can better help us identify patients who can benefit from MT after standard treatment.
TRIAL REGISTRATION
The study protocol was registered at the Chinese Clinical Trial Registry (ChiCTR-IOR-16007939).
目的
探索替加氟/吉美嘧啶/奥替拉西（S1）维持治疗（MT）在一线化疗后有缓解的转移性鼻咽癌（NPC）患者中的安全性和作用，并评估与结局相关的生物标志物。
方法
这是一项多中心、开放标签、随机对照研究，纳入了 2015 年 5 月至 2019 年 5 月在中国五家医院就诊的转移性 NPC 患者。参与者被随机分配至 S1-MT（接受 S1 MT，直至疾病进展或不耐受）或非-MT（随访至疾病进展）组。主要终点是无进展生存期（PFS）。次要终点是总生存期（OS）、EBV-DNA、血清淀粉样蛋白 A（SAA）状态与一线化疗后结局的相关性，以及安全性。
结果
中位随访时间为 24.3 个月；S1-MT 和非-MT 组分别有 88 名和 95 名参与者可进行评估。与非-MT 组相比，S1-MT 延长了 PFS（16.9 个月 vs. 9.3 个月，P<0.001）和 OS（33.6 个月 vs. 20.6 个月，P<0.001）。无论其 EBV-DNA 在一线化疗后的状态如何，参与者都能从 S1 MT 中获益，但 EBV-DNA 阳性的参与者获益更显著（PFS：HR=0.600，95%CI=0.373-0.965，P=0.035；OS：HR=0.393，95%CI=0.227-0.681，P=0.001）。MT 仅改善了一线化疗后 EBV-DNA 下降和 SAA 下降患者的 PFS 和 OS（PFS：HR=0.570，95%CI=0.350-0.919，P=0.021；OS：HR=0.404，95%CI=0.230-0.709，P=0.002）。中位 S1 治疗周期为 23 个。主要不良反应为 1-2 级皮肤色素沉着、口腔黏膜炎和手足综合征。
结论
对于一线化疗有缓解的转移性 NPC 患者，S1 MT 可改善 PFS 和 OS，且耐受性良好。EBV-DNA 和 SAA 可更好地帮助我们识别出在标准治疗后能从 MT 中获益的患者。
试验注册
研究方案在中国临床试验注册中心（ChiCTR-IOR-16007939）注册。
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