Trifluridine/Tipiracil and Oxaliplatin as Induction Chemotherapy in Resectable Esophageal and Gastroesophageal Junction Adenocarcinoma: A Phase II Study

IF 2.9 2区医学 Q2 ONCOLOGY

Cancer Medicine Pub Date : 2025-04-08 DOI:10.1002/cam4.70835

Sarbajit Mukherjee, Yu Fujiwara, Christos Fountzilas, Harsha Pattnaik, Sarah Chatley, Deepak Vadehra, Moshim Kukar, Kristopher Attwood, Anthony George, Shailesh Advani, Han Yu, Kayla Catalfamo, Alyson Brown, Erik Spickard, Arkarachai Fungtammasan, Sagila George, Chih-Yi Liao, Renuka Iyer, Hassan Hatoum

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引用次数: 0

Abstract

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.

Abstract Image

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Trifluridine/Tipiracil和奥沙利铂作为诱导化疗治疗可切除的食管和胃食管交界处腺癌：一项II期研究

背景：术前放化疗（CRT）后手术治疗局限性食管和胃食管结腺癌（EGAC）是一种标准的治疗方法，病理完全缓解（pCR）率为20%。我们评估了一种新的组合，trifluridine/tipiracil与奥沙利铂作为诱导化疗（IC），随后CRT。方法：我们在2020年1月至2022年10月期间招募了可能可切除的局限性EGAC （T3、T4aN0或淋巴结阳性疾病）患者参加这项开放标签、单组、多中心、II期试验。患者接受三个周期的三氟吡啶/替吡拉西和奥沙利铂的IC治疗，然后每周接受卡铂和紫杉醇同步CRT治疗，随后进行手术。主要目的是评估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。循环肿瘤DNA （ctDNA）在预先规定的间隔测量，以评估其与临床结果的相关性。结果22例入组患者中，男性19例（86.4%），白种人20例（90.9%）。中位年龄61岁，12例（54.5%）原发于胃食管交界处。T3病变20例（90.9%），淋巴结阳性15例（68.2%）。只有两名患者有pcr，另外五名患者有接近pcr。由于在中期分析中我们不能达到预先设定的pCR率，因此研究结束。中位随访15.8个月后，2年OS和PFS分别为43%和41%。ctDNA清除率与更高的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例（40.9%）患者的ae为3级或以上。结论与以往报道的单独CRT的pCR相比，三氟吡啶/替吡拉西联合奥沙利铂的IC并没有提高可切除EGAC的pCR率。我们发现ctDNA清除与生存率提高之间存在相关性，值得进一步研究。临床试验信息NCT04097028。

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来源期刊

Cancer Medicine ONCOLOGY-

CiteScore

5.50

自引率

2.50%

发文量

907

审稿时长

19 weeks

期刊介绍： Cancer Medicine is a peer-reviewed, open access, interdisciplinary journal providing rapid publication of research from global biomedical researchers across the cancer sciences. The journal will consider submissions from all oncologic specialties, including, but not limited to, the following areas: Clinical Cancer Research Translational research ∙ clinical trials ∙ chemotherapy ∙ radiation therapy ∙ surgical therapy ∙ clinical observations ∙ clinical guidelines ∙ genetic consultation ∙ ethical considerations Cancer Biology: Molecular biology ∙ cellular biology ∙ molecular genetics ∙ genomics ∙ immunology ∙ epigenetics ∙ metabolic studies ∙ proteomics ∙ cytopathology ∙ carcinogenesis ∙ drug discovery and delivery. Cancer Prevention: Behavioral science ∙ psychosocial studies ∙ screening ∙ nutrition ∙ epidemiology and prevention ∙ community outreach. Bioinformatics: Gene expressions profiles ∙ gene regulation networks ∙ genome bioinformatics ∙ pathwayanalysis ∙ prognostic biomarkers. Cancer Medicine publishes original research articles, systematic reviews, meta-analyses, and research methods papers, along with invited editorials and commentaries. Original research papers must report well-conducted research with conclusions supported by the data presented in the paper.