短程放疗后序贯mFOLFOX-6加阿维鲁单抗治疗局部晚期微卫星稳定型直肠腺癌：Averectal研究

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

作者信息

Shamseddine Ali, Turfa Rim, Chehade Laudy, Zeidan Youssef H, El Husseini Ziad, Kreidieh Malek, Bouferraa Youssef, Elias Charbel, Kattan Joseph, Khalifeh Ibrahim, Mukherji Deborah, Temraz Sally, Shaib Yasser, Soweid Assaad, Alqasem Kholoud, Amarin Rula, Awabdeh Tala Al, Deeba Samer, Doughan Samer, Mohamad Issa, El Khaldi Mousa, Daoud Faiez, Masri Mahmoud Al, Dabous Ali, Hushki Ahmad, Jaber Omar, Jamali Faek, Charafeddine Maya, Darazi Monita Al, Geara Fady

机构信息

Department of Internal Medicine, Division of Hematology/Oncology, Naef K. Basile Cancer Institute - NKBCI, American University of Beirut Medical Center, Beirut, Lebanon.

Department of Internal Medicine, Division of Hematology/Oncology, King Hussein Cancer Center, Amman, Jordan.

出版信息

Eur J Cancer. 2025 Jun 3;222:115428. doi: 10.1016/j.ejca.2025.115428. Epub 2025 Apr 22.

DOI:10.1016/j.ejca.2025.115428

PMID:40286473

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.

摘要

背景

全新辅助治疗（TNT）提高了局部晚期直肠癌（LARC）的完全病理缓解（pCR）率和无病生存率（DFS），不过短程放疗（SCRT）导致局部复发率（LRR）增加令人担忧。免疫疗法与放疗之间的协同作用可能改善LARC的治疗效果，即使存在微卫星稳定（MSS）肿瘤的情况。Averectal试验评估了这些患者接受SCRT，随后进行化疗以及使用阿维鲁单抗进行免疫治疗并接受全直肠系膜切除术（TME）的情况。

方法

在一项由研究者发起的、开放标签、单臂、多中心II期研究中，LARC患者接受SCRT（5Gy×5次分割），每2周进行6个周期的mFOLFOX-6加阿维鲁单抗治疗，随后接受TME。主要结局是pCR与历史对照。次要结局是3年DFS、局部复发率（LR）以及免疫评分（IS）与包括pCR、安全性和生活质量（QoL）在内的结局之间的关联。

结果

在从3个中心入组的44例MSS患者中（2018年7月至2020年10月），40例完成治疗并进行分析（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（11.4,51.4）。15例患者（37.5%）达到pCR；67.5%有主要病理反应。平均DFS为42个月（37.9,46.1）。平均总生存期（OS）为46.3个月（44.4,48.2）。未达到中位DFS和OS。3年DFS为85%。LRR为2.5%。达到pCR与未达到pCR的患者平均IS较高（68对52，p=0.036）。23.5%发生严重不良事件（1例与阿维鲁单抗有关）。3例患者死亡（7.5%），死于疾病进展。基线和末次随访时QoL相似。