Short-course radiation followed by mFOLFOX-6 plus avelumab for locally-advanced microsatellite stable rectal adenocarcinoma: The Averectal study

IF 7.6 1区医学 Q1 ONCOLOGY

European Journal of Cancer Pub Date : 2025-04-22 DOI:10.1016/j.ejca.2025.115428

Ali Shamseddine , Rim Turfa , Laudy Chehade , Youssef H. Zeidan , Ziad El Husseini , Malek Kreidieh , Youssef Bouferraa , Charbel Elias , Joseph Kattan , Ibrahim Khalifeh , Deborah Mukherji , Sally Temraz , Yasser Shaib , Assaad Soweid , Kholoud Alqasem , Rula Amarin , Tala Al Awabdeh , Samer Deeba , Samer Doughan , Issa Mohamad , Fady Geara

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引用次数: 0

Abstract

Background

Total neoadjuvant therapy(TNT) has improved complete pathologic response (pCR) rate and disease-free survival (DFS) in locally advanced rectal cancer (LARC), though an increased local recurrence rate (LRR) with short-course radiotherapy (SCRT) is concerning. Synergism between immunotherapy and radiotherapy may improve outcomes in LARC, even where microsatellite stable (MSS) tumours exist. The Averectal trial evaluated SCRT, followed by chemotherapy and immunotherapy with avelumab and total mesorectal excision (TME) in these patients.

Methods

Patients with LARC received SCRT (5 Gy x5 fractions), 6 cycles of mFOLFOX-6 plus avelumab every 2 weeks, followed by TME in an investigator-initiated, open-label, single-arm, multicentre, phase II study. The primary outcome was pCR vs. historical control. Secondary outcomes were 3-year DFS, local recurrence rate (LR) and the association of the ImmunoScore (IS) with outcomes including pCR, safety, and quality of life (QoL).

Results

Out Of 44 MSS patients enrolled from 3 centres (July 2018 −October 2020), 40 completed treatment and analysed (65 % male, median age 58.5 [31.0, 74.0] years). Median follow-up was 44 months (11.4, 51.4). Fifteen patients (37.5 %) achieved pCR; and 67.5 % had a major pathologic response. Mean DFS was 42 months (37.9, 46.1). Mean OS was 46.3 months (44.4, 48.2). Median DFS and OS were not reached. Three-year DFS was 85 %. LRR was 2.5 %. Patients with vs. without pCR had higher mean IS (68 vs. 52, p = 0.036). Serious adverse events occurred in 23.5 % (one was related to avelumab). Three patients died (7.5 %), due to disease progression. QOL was similar between baseline and last follow-up.

Conclusion

Adding avelumab to neoadjuvant chemotherapy mFOLFOX6 after SCRT, followed by TME, improved pCR without increasing LRR, with acceptable toxicity and QOL.

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短期放疗后mFOLFOX-6加avelumab治疗局部晚期微卫星稳定直肠腺癌：垂直研究

背景：总的新辅助治疗（TNT）改善了局部晚期直肠癌（LARC）的完全病理反应（pCR）率和无病生存（DFS），尽管短期放疗（SCRT）增加了局部复发率（LRR）。免疫治疗和放疗之间的协同作用可能改善LARC的预后，即使存在微卫星稳定（MSS）肿瘤。Averectal试验评估了这些患者的SCRT，随后化疗和免疫治疗联合avelumab和全肠系膜切除术（TME）。方法LARC患者接受SCRT（5个 Gy x5分数），每2周6个周期mFOLFOX-6加avelumab，随后进行TME，这是一项研究者发起的、开放标签、单臂、多中心的II期研究。主要结果是pCR与历史对照。次要结果为3年DFS、局部复发率（LR）和免疫评分（IS）与pCR、安全性和生活质量（QoL）等结果的相关性。结果从3个中心（2018年7月 - 2020年10月）入组的44例MSS患者中，有40例完成了治疗和分析（65 %为男性，中位年龄58.5[31.0,74.0]岁）。中位随访时间为44个月（11.4个月，51.4个月）。15例（37.5% %）实现pCR；67.5% %有重大病理反应。平均DFS为42个月（37.9,46.1）。平均OS为46.3个月（44.4个月，48.2个月）。未达到中位DFS和OS。3年DFS为85 %。LRR为2.5 %。采用pCR的患者与未采用pCR的患者相比，平均IS更高（68比52，p = 0.036）。23.5% %发生严重不良事件（1例与avelumab相关）。由于疾病进展，3例患者死亡（7.5% %）。生活质量在基线和最后一次随访期间相似。结论在SCRT后新辅助化疗mFOLFOX6中加入avelumab，再加入TME，可改善pCR，但LRR未升高，毒副作用和生活质量均可接受。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

European Journal of Cancer 医学-肿瘤学

CiteScore

11.50

自引率

4.80%

发文量

953

审稿时长

23 days

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