Güller Ulrich, Hayoz Stefanie, Horber Daniel, Jochum Wolfram, De Dosso Sara, Koeberle Dieter, Schacher Sabina, Inauen Roman, Stahl Michael, Delaunoit Thierry, Ettrich Thomas, Bodoky György, Michel Pierre, Koessler Thibaud, Rothgiesser Karin, Calmonte Sandra, Joerger Markus
Oncology & Hematology Center Thun-Berner Oberland, Spital STS AG, Thun, Switzerland.
Swiss Group for Clinical Cancer Research (SAKK) Competence Center, Bern, Switzerland.
Clin Cancer Res. 2025 Mar 11. doi: 10.1158/1078-0432.CCR-24-4048.
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).
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.
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.
我们评估了辅助使用阿司匹林对已切除的PIK3CA突变型结肠癌患者的益处。
这是一项III期、前瞻性、随机、安慰剂对照、双盲、多中心、跨国试验。纳入了患有激活型PIK3CA突变的II期和III期结肠癌切除患者。由于资金限制，试验提前结束。随机分组比例为2:1，分别给予每日100mg阿司匹林或安慰剂，持续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）。
总体而言，对1040例患者进行了PIK3CA突变筛查，112例被随机分为阿司匹林组（N = 74）和安慰剂组（N = 38）。中位年龄为66岁，女性占42.9%。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的风险比（HR）为0.57（90%置信区间：0.27 - 1.22），倾向于阿司匹林（p = 0.11）。阿司匹林组5年DFS率为86.5%（90%置信区间：77.7% - 92.0%），安慰剂组为72.9%（90%置信区间：55.7% - 84.3%）。TTR的HR为0.49（90%置信区间：0.21 - 1.19，p = 0.089），倾向于阿司匹林。没有患者经历与阿司匹林相关的严重不良事件。
SAKK 41/13是第一项提供临床证据证明辅助使用阿司匹林对已切除的PIK3CA突变型结肠癌患者有保护作用的随机试验，DFS和TTR有临床相关改善。尽管由于研究提前结束结果无统计学意义，但辅助使用阿司匹林值得II期和III期已切除的PIK3CA突变型结肠癌患者个体化考虑。
