美国布列根和妇女医院Michelle D. Holmes团队比较了阿司匹林与安慰剂作为乳腺癌的辅助治疗对患者预后的影响。这一研究成果发表在2024年4月29日出版的《美国医学会杂志》上。

对乳腺癌幸存者的观察研究和阿司匹林治疗心血管疾病的前瞻性试验表明，阿司匹林使用者的癌症生存率有所提高，但缺乏阿司匹林预防癌症复发的前瞻性研究。

为了探讨阿司匹林是否能降低癌症幸存者发生侵袭性癌症事件的风险，研究组在美国和加拿大进行了一项3期随机、安慰剂对照、双盲试验（A011502），共有3020名患有高危非转移性乳腺癌参与者，从2017年1月6日至2020年12月4日，从534个地点招募参与者，随访至2023年3月4日。参与者被随机分组（根据激素受体状态[阳性与阴性]、体重指数[≤30 vs>30]、II期与III期以及诊断后时间[<18 vs≥18个月]进行分层），接受300mg阿司匹林（n = 1510）或安慰剂（n = 1510），持续治疗5年。主要结局是无侵袭性疾病生存。总生存率是一个关键次要结局。

当数据和安全监测委员会建议在第一次中期分析时暂停研究时，共有3020名参与者被随机分组，因为风险比已经超过了预先指定的无效界限。中位随访时间为33.8个月（范围为0.1-72.6个月），观察到253例无侵袭性疾病生存事件（阿司匹林组141例，安慰剂组112例），风险比为1.27（95%CI，0.99-1.63；P = .06）。阿司匹林组的所有无侵袭性疾病生存事件，包括死亡、侵袭性进展（包括远处和局部）和新的原发事件，在数量上都更高，尽管差异没有统计学意义。两组的总生存率无差异（危险比1.19；95%可信区间0.82-1.72）。两组的3级和4级不良事件发生率相似。

研究结果表明，在患有高危非转移性癌症的参与者中，在早期随访中，每日阿司匹林治疗并不能改善癌症复发或存活的风险。尽管阿司匹林有前景且广泛可用，但不应推荐其作为癌症的辅助治疗。

附：英文原文

Title: Aspirin vs Placebo as Adjuvant Therapy for Breast Cancer: The Alliance A011502 Randomized Trial

Author: Wendy Y. Chen, Karla V. Ballman, Ann H. Partridge, Olwen M. Hahn, Frederick M. Briccetti, William J. Irvin, Banu Symington, Kala Visvanathan, Paula R. Pohlmann, Thomas H. Openshaw, Anna Weiss, Eric P. Winer, Lisa A. Carey, Michelle D. Holmes

Issue&Volume: 2024-04-29

Abstract:

Importance  Observational studies of survivors of breast cancer and prospective trials of aspirin for cardiovascular disease suggest improved breast cancer survival among aspirin users, but prospective studies of aspirin to prevent breast cancer recurrence are lacking.

Objective  To determine whether aspirin decreases the risk of invasive cancer events among survivors of breast cancer.

Design, Setting, and Participants  A011502, a phase 3, randomized, placebo-controlled, double-blind trial conducted in the United States and Canada with 3020 participants who had high-risk nonmetastatic breast cancer, enrolled participants from 534 sites from January 6, 2017, through December 4, 2020, with follow-up to March 4, 2023.

Interventions  Participants were randomized (stratified for hormone receptor status [positive vs negative], body mass index [≤30 vs >30], stage II vs III, and time since diagnosis [<18 vs ≥18 months]) to receive 300 mg of aspirin (n=1510) or placebo once daily (n=1510) for 5 years.

Main Outcomes and Measures  The primary outcome was invasive disease–free survival. Overall survival was a key secondary outcome.

Results  A total of 3020 participants were randomized when the data and safety monitoring committee recommended suspending the study at the first interim analysis because the hazard ratio had crossed the prespecified futility bound. By median follow-up of 33.8 months (range, 0.1-72.6 months), 253 invasive disease–free survival events were observed (141 in the aspirin group and 112 in the placebo group), yielding a hazard ratio of 1.27 (95% CI, 0.99-1.63; P=.06). All invasive disease–free survival events, including death, invasive progression (both distant and locoregional), and new primary events, were numerically higher in the aspirin group, although the differences were not statistically significant. There was no difference in overall survival (hazard ratio, 1.19; 95% CI, 0.82-1.72). Rates of grades 3 and 4 adverse events were similar in both groups.

Conclusion and Relevance  Among participants with high-risk nonmetastatic breast cancer, daily aspirin therapy did not improve risk of breast cancer recurrence or survival in early follow-up. Despite its promise and wide availability, aspirin should not be recommended as an adjuvant breast cancer treatment.

DOI: 10.1001/jama.2024.4840

Source: https://jamanetwork.com/journals/jama/fullarticle/2818110