Assessment of Ovarian Function in Phase III (Neo)Adjuvant Breast Cancer Clinical Trials: A Systematic Evaluation
Assessment of Ovarian Function in Phase III (Neo)Adjuvant Breast Cancer Clinical Trials: A Systematic Evaluation
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DOI：
10.1093/jnci/djab111
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发表时间：
2021-05-28
影响因子：
10.3
通讯作者：
Phillips, Kelly-Anne
中科院分区：
文献类型：
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作者：
Cui, Wanyuan;Francis, Prudence A.;Phillips, Kelly-Anne
背景：卵巢功能丧失是公认的乳腺癌化疗不良反应，对患者非常重要。人们对新癌症疗法的卵巢毒性知之甚少。本研究考察了乳腺癌临床试验是否包括试验干预对卵巢功能影响的评估。方法：符合条件的试验是2008年6月至2019年10月期间招募的乳腺癌药物治疗的III期（新）辅助试验，其中包括绝经前妇女。检索了MEDLINE、EMBASE、Clinicaltrials.gov和EudraCT。数据从试验出版物、方案、数据库和发给所有试验主席的调查中提取。统计学显著性检验为双侧检验。结果：在确定的2354份记录中，有141项试验符合条件。研究治疗包括化疗（36.9%）、HER2靶向（24.8%）、内分泌（12.8%）、免疫治疗（7.8%）、细胞周期蛋白依赖性激酶4/6抑制剂（5.0%）和聚adp核糖聚合酶抑制剂（2.8%）。在13项（9.2%）试验中，卵巢功能是预先指定的终点。45项（31.9%）试验收集了卵巢功能数据，但只有33项（23.4%）试验收集了试验干预后的数据。常见的干预后数据包括月经（15.6%）、妊娠（13.5%）、雌二醇（9.9%）和促卵泡激素水平（8.5%）。只有4项（2.8%）试验收集干预后的抗苗勒管激素水平，3项（2.1%）试验收集心房卵泡计数。在22项研究免疫疗法、细胞周期蛋白依赖性激酶4/6抑制剂或聚二磷酸聚合酶抑制剂的试验中，没有一项将卵巢功能作为终点，但有4项（18.2%）收集了干预后卵巢功能数据。结论：在包括绝经前妇女的III期乳腺癌（新）辅助试验中，很少评估药物干预对卵巢功能的影响。考虑到卵巢功能终点对知情决策的重要性，试验人员在设计临床试验时应考虑纳入卵巢功能终点。
Background: Loss of ovarian function is a recognized adverse effect of chemotherapy for breast cancer and of great importance to patients. Little is known about the ovarian toxicity of newer cancer treatments. This study examined whether breast cancer clinical trials include assessment of the impact of trial interventions on ovarian function. Methods: Eligible trials were phase III (neo)adjuvant trials of pharmacologic treatments for breast cancer, recruiting between June 2008 and October 2019, which included premenopausal women. MEDLINE, EMBASE, Clinicaltrials.gov, and EudraCT were searched. Data were extracted from trial publications, protocols, databases, and a survey sent to all trial chairs. Tests of statistical significance were 2-sided. Results: Of 2354 records identified, 141 trials were eligible. Investigational treatments included chemotherapy (36.9%), HER2 targeted (24.8%), endocrine (12.8%), immunotherapy (7.8%), cyclin-dependent kinase 4/6 inhibitors (5.0%), and poly-ADP-ribose polymerase inhibitors (2.8%). Ovarian function was a prespecified endpoint in 13 (9.2%) trials. Forty-five (31.9%) trials collected ovarian function data, but only 33 (23.4%) collected posttrial-intervention data. Common postintervention data collected included menstruation (15.6%), pregnancy (13.5%), estradiol (9.9%), and follicle-stimulating hormone levels (8.5%). Only 4 (2.8%) trials collected postintervention anti-mullerian hormone levels, and 3 (2.1%) trials collected antral follicle count. Of 22 trials investigating immunotherapy, cyclin-dependent kinase 4/6 inhibitors, or poly-ADPribose polymerase inhibitors, none specified ovarian function as an endpoint, but 4 (18.2%) collected postintervention ovarian function data. Conclusions: The impact of pharmacologic interventions on ovarian function is infrequently assessed in phase III breast cancer (neo)adjuvant trials that include premenopausal women. Trialists should consider inclusion of ovarian function endpoints when designing clinical trials, given its importance for informed decision making.