曲氟尿苷/替匹嘧啶与奥沙利铂作为可切除食管及食管胃交界腺癌诱导化疗的II期研究
Trifluridine/Tipiracil and Oxaliplatin as Induction Chemotherapy in Resectable Esophageal and Gastroesophageal Junction Adenocarcinoma: A Phase II Study.
作者信息
Mukherjee Sarbajit, Fujiwara Yu, Fountzilas Christos, Pattnaik Harsha, Chatley Sarah, Vadehra Deepak, Kukar Moshim, Attwood Kristopher, George Anthony, Advani Shailesh, Yu Han, Catalfamo Kayla, Brown Alyson, Spickard Erik, Fungtammasan Arkarachai, George Sagila, Liao Chih-Yi, Iyer Renuka, Hatoum Hassan
机构信息
Roswell Park Comprehensive Cancer Center, Buffalo, New York, USA.
Miami Cancer Institute, Baptist Health South Florida, Miami, Florida, USA.
出版信息
Cancer Med. 2025 Apr;14(7):e70835. doi: 10.1002/cam4.70835.
BACKGROUND
Preoperative chemoradiation (CRT) followed by surgery for localized esophageal and gastroesophageal junction adenocarcinoma (EGAC) is a standard of care with a pathologic complete response (pCR) rate of 20%. We evaluated a novel combination of trifluridine/tipiracil with oxaliplatin as induction chemotherapy (IC) followed by CRT.
METHODS
We enrolled patients with potentially resectable localized EGAC (T3, T4aN0, or node-positive disease) in this open-label, single-arm, multicenter, Phase II trial between January 2020 and October 2022. Patients received three cycles of IC with trifluridine/tipiracil and oxaliplatin and then underwent concurrent CRT with weekly carboplatin and paclitaxel followed by surgery. The primary objective was to evaluate the pCR rate. The secondary objectives were to evaluate 2-year progression-free survival (PFS), 2-year overall survival (OS), and toxicities. Circulating tumor DNA (ctDNA) was measured at prespecified intervals to assess its correlation with clinical outcomes.
RESULTS
Of the 22 enrolled patients, 19 (86.4%) were male and 20 (90.9%) were Caucasian. The median age was 61 years, and 12 (54.5%) had their primary disease at the gastroesophageal junction. Twenty (90.9%) patients had T3 disease, and 15 (68.2%) had node-positive disease. Only two patients had pCRs, and an additional five had near pCRs. Since we could not meet our predefined pCR rate at the interim analysis, the study was closed. After a median follow-up of 15.8 months, 2-year OS and PFS were 43% and 41%, respectively. ctDNA clearance was associated with a significantly higher OS rate (p = 0.012) and PFS rate (p = 0.008). Nausea (59.1%) and fatigue (59.1%) were common treatment-related adverse events (AEs); nine (40.9%) patients had Grade 3 or higher AEs.
CONCLUSION
IC with trifluridine/tipiracil and oxaliplatin followed by CRT did not improve pCR rate in resectable EGAC compared to pCR from previous reports with CRT alone. We found a correlation between ctDNA clearance and improved survival, which merits further investigation.
CLINICAL TRIAL INFORMATION
NCT04097028.
背景
术前同步放化疗（CRT）后行手术治疗局限性食管及食管胃交界腺癌（EGAC）是一种标准治疗方案，病理完全缓解（pCR）率为20%。我们评估了曲氟尿苷/替匹嘧啶与奥沙利铂联合作为诱导化疗（IC），随后进行CRT的新方案。
方法
在2020年1月至2022年10月期间，我们在这项开放标签、单臂、多中心II期试验中纳入了具有潜在可切除局限性EGAC（T3、T4aN0或淋巴结阳性疾病）的患者。患者接受三个周期的曲氟尿苷/替匹嘧啶与奥沙利铂IC治疗，然后接受每周一次卡铂和紫杉醇的同步CRT治疗，随后进行手术。主要目标是评估pCR率。次要目标是评估2年无进展生存期（PFS）、2年总生存期（OS）和毒性。在预定时间间隔测量循环肿瘤DNA（ctDNA），以评估其与临床结局的相关性。
结果
在22名入组患者中，19名（86.4%）为男性，20名（90.9%）为白种人。中位年龄为61岁，12名（54.5%）患者的原发疾病位于食管胃交界。20名（90.9%）患者患有T3期疾病，15名（68.2%）患者有淋巴结阳性疾病。只有两名患者达到pCR，另外五名患者接近pCR。由于在中期分析时我们未达到预定的pCR率，该研究提前终止。中位随访15.8个月后，2年OS率和PFS率分别为43%和41%。ctDNA清除与显著更高的OS率（p = 0.012）和PFS率（p = 0.008）相关。恶心（59.1%）和疲劳（59.1%）是常见的治疗相关不良事件（AE）；9名（40.9%）患者发生3级或更高等级的AE。
结论
与既往单独CRT报告的pCR率相比，曲氟尿苷/替匹嘧啶与奥沙利铂IC后行CRT并未提高可切除EGAC的pCR率。我们发现ctDNA清除与生存期改善之间存在相关性，这值得进一步研究。
临床试验信息
NCT04097028。
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