ASCO Issues New Recommendations Aimed to Address Ovarian Toxicity in Cancer Clinical Trials
ASCO recently released a research statement titled “Measuring Ovarian Toxicity in Clinical Trials,” published in Lancet Oncology. This statement outlines new recommendations for assessing ovarian toxicity in cancer clinical trials, underlining the urgency of understanding the long-term impacts of cancer therapies on ovarian function. It is documented that a number of cancer drugs negatively impact the ovaries. Each year, approximately 1.4 million women under the age of 45 are diagnosed with cancer worldwide. Many of them receive cancer treatments that can potentially harm their ovaries, leading to premature menopause. Premature menopause not only results in infertility but also has adverse effects on bone and cardiovascular health. Most cancer clinical trials currently do not collect information on whether the studied anticancer treatments cause ovarian toxicity. For example, from 2008 to 2019, only 9% of phase III breast cancer trials specifically investigated the impact of treatments on ovarian function.
Recent studies have also shown that certain chemotherapeutic drugs, including cyclophosphamide, cisplatin, and doxorubicin, can have detrimental effects on various cellular components of the ovary. These drugs can lead to a rapid depletion of the ovarian follicular reserve, ultimately causing premature ovarian insufficiency. The mechanisms behind this include the induction of primordial follicle death and/or accelerated activation, as well as an increase in the atresia of growing follicles. Additionally, these drugs can cause damage to blood vessels and the stromal compartment of the ovary while also promoting inflammation in the ovarian tissue.
Julie R. Gralow, MD, FACP, FASCO, ASCO’s Chief Medical Officer, and Executive Vice President, emphasized the significance of addressing this knowledge gap: “We’ve long been aware that cancer treatments can significantly impact fertility and increase the risk for certain diseases. However, this issue has been inadequately addressed in clinical trials. This knowledge shortfall compromises the ability of clinicians and patients to make well-informed treatment choices.”
ASCO’s released new recommendations aim to rectify this issue by establishing guidelines for assessing ovarian toxicity in clinical trials. Key recommendations include:
- Inclusion of Ovarian Toxicity Measurement: Assess ovarian toxicity in all relevant clinical trials, especially those focused on curative intent or primary prevention, for premenopausal and post-pubertal patients with ovaries. Consider ovarian toxicity assessment in trials for advanced and metastatic cancer, particularly in treatment-naïve patients.
- Timeframes for Data Collection: Collect ovarian function measures at baseline and 12–24 months after discontinuing the anticancer agent, at a minimum. For trials where ovarian toxicity mechanisms, extent, and recovery times are unknown, additional data collection every 6–12 months during treatment and after treatment cessation is recommended.
- Use of Clinical Measures and Biomarkers: Assess both clinical measures and biomarkers of ovarian function. If biomarkers cannot be assessed, collect data on clinical measures such as menstruation, pregnancy, live births, and information on possible confounders like surgeries and hormone use.
Wanda Cui, MBBS BMedSci FRACP, lead author of the ASCO statement, emphasized the importance of these recommendations: “Our new recommendations aim to fill this void by encouraging researchers to collect these essential data and offering them a framework to do so. The ultimate goal is to empower individuals with comprehensive information about the risks they may face, from fertility concerns to other long-term health implications from early-onset menopause.”