术后多西他赛联合顺铂放疗与单纯手术治疗高危口腔鳞状细胞癌的随机Ⅱ期临床试验：以 ITGB1 为潜在预测生物标志物的探索性分析
Postoperative radiotherapy with docetaxel versus cisplatin for high-risk oral squamous cell carcinoma: a randomized phase II trial with exploratory analysis of ITGB1 as a potential predictive biomarker.
机构信息
Department of Oral and Maxillofacial-Head Neck Oncology, Division of Radiation Oncology, College of Stomatology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Shanghai, China.
出版信息
BMC Med. 2024 Jul 29;22(1):314. doi: 10.1186/s12916-024-03541-6.
BACKGROUND
Oral squamous cell carcinoma (OSCC) causes significant mortality and morbidity worldwide. Surgical resection with adjuvant radiotherapy remains the standard treatment for locally advanced resectable OSCC. Results from landmark trials have established postoperative concurrent cisplatin-radiotherapy (Cis-RT) as the standard treatment for OSCC patients with high-risk pathologic features. However, cisplatin-related toxicity limits usage in clinical practice. Given the need for effective but less toxic alternatives, we previously conducted a single-arm trial showing favorable safety profiles and promising efficacy of concurrent docetaxel-radiotherapy (Doc-RT).
METHODS
In this randomized phase 2 trial, we aimed to compare Doc-RT with the standard Cis-RT in postoperative OSCC patients. Eligible patients had AJCC stage III-IV resectable OSCC with high-risk pathologic features. Two hundred twenty-four patients were enrolled and randomly assigned to receive concurrent Doc-RT or Cis-RT. The primary endpoint was 2-year disease-free survival (DFS). Secondary endpoints included overall survival (OS), locoregional-free survival (LRFS), distant metastasis-free survival (DMFS), and adverse events (AEs). Integrin β1 (ITGB1) expression was analyzed as a biomarker for efficacy.
RESULTS
After a median 28.8-month follow-up, 2-year DFS rates were 63.7% for Doc-RT arm and 56.1% for Cis-RT arm (p = 0.55). Meanwhile, Doc-RT demonstrated comparable efficacy to Cis-RT in OS, LRFS, and DMFS. Doc-RT resulted in fewer grade 3 or 4 hematological AEs. Low ITGB1 was associated with improved Doc-RT efficacy versus Cis-RT.
CONCLUSIONS
This randomized trial directly compared Doc-RT with Cis-RT for high-risk postoperative OSCC patients, with comparable efficacy and less toxicity. ITGB1 merits further validation as a predictive biomarker to identify OSCC patients most likely to benefit from Doc-RT. Findings indicate docetaxel may be considered as a concurrent chemoradiation option in this setting.
TRIAL REGISTRATION
www.
CLINICALTRIALS
gov . NCT02923258 (date of registration: October 4, 2016).
背景
口腔鳞状细胞癌（OSCC）在全球范围内导致了较高的死亡率和发病率。手术切除联合辅助放疗仍然是局部晚期可切除 OSCC 的标准治疗方法。来自标志性试验的结果已经确立了术后顺铂放疗（Cis-RT）作为具有高危病理特征的 OSCC 患者的标准治疗方法。然而，顺铂相关的毒性限制了其在临床实践中的应用。鉴于需要有效的但毒性较小的替代药物，我们之前进行了一项单臂试验，显示了同步多西紫杉醇放疗（Doc-RT）的良好安全性和有前途的疗效。
方法
在这项随机的 2 期试验中，我们旨在比较 Doc-RT 与术后 OSCC 患者的标准 Cis-RT。符合条件的患者为 AJCC 分期 III-IV 期可切除的 OSCC，且具有高危病理特征。共纳入 224 例患者，并随机分为接受同步 Doc-RT 或 Cis-RT。主要终点是 2 年无病生存率（DFS）。次要终点包括总生存率（OS）、局部区域无复发生存率（LRFS）、远处无转移生存率（DMFS）和不良事件（AEs）。整合素β1（ITGB1）表达被分析为疗效的生物标志物。
结果
在中位随访 28.8 个月后，Doc-RT 组的 2 年 DFS 率为 63.7%，Cis-RT 组为 56.1%（p=0.55）。同时，Doc-RT 在 OS、LRFS 和 DMFS 方面与 Cis-RT 具有相当的疗效。Doc-RT 导致较少的 3 级或 4 级血液学不良事件。低 ITGB1 与 Doc-RT 相对于 Cis-RT 的疗效改善相关。
结论
这项随机试验直接比较了 Doc-RT 与 Cis-RT 用于高危术后 OSCC 患者，疗效相当，毒性更小。ITGB1 作为一种预测生物标志物，有望进一步验证，以确定最有可能从 Doc-RT 中获益的 OSCC 患者。研究结果表明，多西紫杉醇在这种情况下可被认为是一种同步放化疗的选择。
试验注册
www.
临床试验
gov. NCT02923258（注册日期：2016 年 10 月 4 日）。
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