Assessment of Ovarian Function in Phase 3 (Neo)adjuvant Breast Cancer Clinical Trials: A Systematic Evaluation
A partir d'une revue systématique de la littérature publiée entre 2008 et 2019, cette étude analyse la prise en compte, dans les essais de phase III, de l'impact des traitements pharmacologiques adjuvants ou néoadjuvants sur la fonction ovarienne des patientes atteintes d'un cancer du sein
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 3 (neo)adjuvant trials of pharmacologic treatments for breast cancer recruiting between June 2008-October 2019, which included premenopausal women. MEDLINE, EMBASE, Clinicaltrials.gov, EudraCT were searched. Data were extracted from trial publications, protocols, databases, and a survey sent to all trial chairs. Tests of statistical significance were two-sided. PROSPERO registration CRD42019134551. Results : Of 2,354 records identified, 141 trials were eligible. Investigational treatments included chemotherapy (36.9%), HER2-targeted (24.8%), endocrine (12.8%), immunotherapy (7.8%), CDK4/6-inhibitors (5.0%), PARP-inhibitors (2.8%). Ovarian function was a pre-specified endpoint in 13 (9.2%) trials. Forty-five (31.9%) trials collected ovarian function data, but only 33 (23.4%) collected post-trial-intervention data. Common post-intervention data collected included menstruation (15.6%), pregnancy (13.5%), estradiol (9.9%) and follicle-stimulating hormone levels (8.5%). Only four (2.8%) trials collected post-intervention anti-mullerian hormone levels and three (2.1%) trials collected antral follicle count. Of 22 trials investigating immunotherapy, CDK4/6-inhibitors or PARP-inhibitors, none specified ovarian function as an endpoint, but four (18.2%) collected post-intervention ovarian function data. Conclusions : The impact of pharmacologic interventions on ovarian function is infrequently assessed in phase 3 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.