Adjuvant Aspirin Treatment in PIK3CA Mutated Colon Cancer Patients: The SAKK 41/13 - Prospective Randomized Placebo-Controlled Double-Blind Trial

IF 10 1区医学 Q1 ONCOLOGY

Clinical Cancer Research Pub Date : 2025-03-11 DOI:10.1158/1078-0432.ccr-24-4048

Ulrich Güller, Stefanie Hayoz, Daniel Horber, Wolfram Jochum, Sara De Dosso, Dieter Koeberle, Sabina Schacher, Roman Inauen, Michael Stahl, Thierry Delaunoit, Thomas Ettrich, György Bodoky, Pierre Michel, Thibaud Koessler, Karin Rothgiesser, Sandra Calmonte, Markus Joerger

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引用次数: 0

Abstract

Purpose: We assessed the benefit of adjuvant aspirin in resected PIK3CA-mutated colon cancer patients. Patients & Methods: This was a phase III, prospective, randomized, placebo-controlled, double-blind, multicenter, and multinational trial. Patients with resected colon cancer stage II and III harbouring an activating PIK3CA mutation were included. Due to financial constraints, the trial was prematurely closed. Randomization was 2:1 to aspirin 100mg versus placebo daily for 3 years. The primary endpoint was disease-free survival (DFS). Secondary endpoints included the time to disease recurrence (TTR), overall survival, and adverse events (AE). Results: Overall, 1,040 patients were screened for PIK3CA mutations, with 112 randomized to aspirin (N=74) and placebo (N=38). Median age was 66 years and 42.9% were female. After a median follow-up of 4 years, 19 DFS events occurred, including 10 in the aspirin and nine in the placebo arm. The HR for DFS was 0.57 (90%CI: 0.27-1.22), in favor of aspirin (p=0.11). DFS rates at 5 years were 86.5% (90%CI: 77.7%-92.0%) in the aspirin and 72.9% (90%CI: 55.7%-84.3%) in the placebo arm. The HR for TTR was 0.49 (90%CI: 0.21-1.19, p=0.089) in favor of aspirin. No patient experienced aspirin-related serious AEs. Conclusions: The SAKK 41/13 is the first randomized trial to provide clinical evidence of a protective effect of adjuvant aspirin in resected PIK3CA-mutant colon cancer patients, with clinically relevant DFS and TTR improvements. Although results were not statistically significant due to premature study closure, adjuvant aspirin warrants individual consideration in patients with resected PIK3CA-mutant colon cancer stage II and III.

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目的：我们评估了阿司匹林辅助治疗对切除的 PIK3CA 突变结肠癌患者的益处。患者及样本；方法：这是一项 III 期、前瞻性、随机、安慰剂对照、双盲、多中心和跨国试验。研究对象包括PIK3CA突变激活的II期和III期切除结肠癌患者。由于资金紧张，试验提前结束。试验以 2:1 的比例随机分配阿司匹林 100 毫克与安慰剂的每日剂量，为期 3 年。主要终点是无病生存期（DFS）。次要终点包括疾病复发时间（TTR）、总生存期和不良事件（AE）。研究结果共有1040名患者接受了PIK3CA突变筛查，其中112人随机接受了阿司匹林治疗（74人）和安慰剂治疗（38人）。中位年龄为66岁，42.9%为女性。中位随访4年后，发生了19例DFS事件，其中阿司匹林组10例，安慰剂组9例。DFS的HR为0.57（90%CI：0.27-1.22），阿司匹林更优（P=0.11）。阿司匹林治疗组 5 年的 DFS 率为 86.5%（90%CI：77.7%-92.0%），安慰剂治疗组为 72.9%（90%CI：55.7%-84.3%）。TTR 的 HR 为 0.49（90%CI：0.21-1.19，p=0.089），阿司匹林更优。没有患者出现与阿司匹林相关的严重不良反应。结论SAKK 41/13是首个随机试验，提供了阿司匹林辅助治疗对切除的PIK3CA突变结肠癌患者有保护作用的临床证据，并改善了临床相关的DFS和TTR。虽然由于研究过早结束，结果不具有统计学意义，但对于切除的 PIK3CA 突变结肠癌 II 期和 III 期患者来说，阿司匹林辅助治疗值得单独考虑。

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来源期刊

Clinical Cancer Research 医学-肿瘤学

CiteScore

20.10

自引率

1.70%

发文量

1207

审稿时长

2.1 months

期刊介绍： Clinical Cancer Research is a journal focusing on groundbreaking research in cancer, specifically in the areas where the laboratory and the clinic intersect. Our primary interest lies in clinical trials that investigate novel treatments, accompanied by research on pharmacology, molecular alterations, and biomarkers that can predict response or resistance to these treatments. Furthermore, we prioritize laboratory and animal studies that explore new drugs and targeted agents with the potential to advance to clinical trials. We also encourage research on targetable mechanisms of cancer development, progression, and metastasis.