Wanyuan Cui1,2, Prudence A Francis1, Sherene Loi2,3, Martha Hickey4,5, Catharyn Stern5,6, Lumine Na7, Ann H Partridge8, Sibylle Loibl9,10, Richard A Anderson11, Karla J Hutt12, Louise A Keogh13, Kelly-Anne Phillips1,2,14. 1. Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia. 2. The Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, VIC, Australia. 3. Division of Research, Peter MacCallum Cancer Centre, Melbourne, Australia. 4. Department of Obstetrics and Gynaecology, University of Melbourne, Parkville, VIC, Australia. 5. Royal Women Hospital, Parkville, VIC, Australia. 6. Melbourne IVF, East Melbourne, VIC, Australia. 7. Peter MacCallum Cancer Centre, Melbourne, Australia. 8. Dana-Farber Cancer Institute, Boston, MA, United States of America. 9. German Breast Group, Neu-Isenburg, Germany. 10. Centre for Haematology and Oncology, Bethanien, Frankfurt, Germany. 11. MRC Centre for Reproductive Health, University of Edinburgh, UK. 12. Department of Anatomy and Developmental Biology, Biomedicine Discovery Institute, Monash University, Clayton, VIC, Australia. 13. Centre for Health Equity, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, VIC, Australia. 14. Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Australia.
Abstract
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.
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.
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