Assessment of ovarian function as an endpoint in breast cancer clinical trials: A systematic review.

Abstract

e14098 Background: Premature ovarian failure (POF) is an established adverse effect of chemotherapy for breast cancer (BC); little is known about the ovarian toxicity of newer treatments (e.g. PARPi, CDK4/6 inhibitors, immunotherapy, anti-HER2 therapy). This study examined whether contemporary BC (neo)adjuvant clinical trials will provide data on POF. Methods: Eligible studies were phase 3 (neo)adjuvant trials of pharmacologic agents aimed to reduce BC events, that enrolled premenopausal women between June 2008 - Sept 2019. MEDLINE and EMBASE were searched using MESH terms / keywords: “breast neoplasm” or “breast adj2 (cancer* or tumo?r* or carcinoma*)”, “adjuvant chemotherapy” or “neoadjuvant therapy” or “neoadjuvant” or “adjuvant”. Clinicaltrials.gov and EudraCT were searched using the filters “breast cancer”, “interventional studies”, “phase 3”. Data extracted from eligible trial publications, protocols and clinicaltrials.gov/EudraCT summaries, included whether each trial assessed the variables - post treatment pregnancy/birth, attempt at pregnancy, menstrual data, antral follicle count, FSH, LH, estrogen, progesterone and AMH levels. Results: Of 1665 trials screened, 141 were eligible. Investigational treatments included chemotherapy (71%), endocrine (20%), anti-HER2 (26%), immunotherapy (8%), CDK4/6 inhibitor (5%), PARPi (2%). Few trials (28%) assessed quality of life (QOL). Study chairs were from Nth America (19%), Europe (36%), Asia (43%); most (67%) were male. POF and fertility measures were prespecified endpoints in 9 (6%) and 0 trials respectively. Twenty (14%) trials collected POF and/or fertility data; post treatment pregnancy (11/20), amenorrhoea (6/20), estrogen (8/20), FSH (7/20), LH (5/20), AMH (3/20), and progesterone levels (1/20) and antral follicle count (3/20). Assessment of POF was associated with collection of QOL data (p = 0.02) but not with BC phenotype, timing, treatment type, or sex or nationality of study chair. Conclusions: POF measures are rarely prespecified endpoints and are infrequently collected in phase 3 BC (neo)adjuvant trials. Trialists should consider POF, given the potential for this data to enhance informed decision making for premenopausal patients.