Monitoring ovarian function in oncology studies

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Published: 1 Jun 2024
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Dr Elizabeth Trice Loggers - University of Washington, Seattle, USA

Dr Loggers talks to ecancer at ASCO 2024 about results and insights from the DeFi phase 3 study of nirogacestat in desmoid tumours.

In DeFi, 75% of ‘females of reproductive potential’ treated with nirogacestat experienced ovarian toxicity. Most events resolved, including in 100% who stopped treatment for any reason, suggesting ovarian toxicity with nirogacestat is transient.

Though initiated prior to the ASCO guidance, ovarian toxicity assessments in DeFi generally align with and support the use of both clinical measures and hormone biomarkers in oncology clinical trials.

Monitoring ovarian function in oncology studies

Dr Elizabeth Trice Loggers - University of Washington, Seattle, USA

Today I was presenting on ovarian toxicity that was observed in the DeFi phase II study of nirogacestat. This particular abstract focussed on a 2023 research statement that was published by ASCO recommending that investigators include measures of ovarian toxicity in all of their clinical trials. So we were using DeFi as an example of a study that embedded within it measures of ovarian toxicity in its resolution.

What are the results?

So what’s important to know is that nirogacestat is an oral gamma secretase inhibitor, it’s the only FDA-approved therapy for desmoid tumour. In that trial we observed that 75% of females of reproductive potential actually did have ovarian toxicity and that 78% of those cases resolved. What was really important is that 100% of those cases resolved when people stopped nirogacestat for any reason and 71% of them resolved actually while people were still on treatment. So it’s clear that for this therapy ovarian toxicity is likely temporary and will resolve in time. This was corroborated with menstrual diaries and actual hormonal measures that were taken while on treatment and then after the cessation of treatment. This was consistent with those ASCO guidelines that we measure ovarian toxicity both through clinical measures like menstrual diaries and then also with hormonal measures as well.

What could be the impact of this research?

So the importance of this work is that historically measures of ovarian toxicity have not been included in trials. So, for example, one study suggests that these measures have been included in only 9% of neoadjuvant breast cancer trials which you could imagine are a highly likely population to be fertile and to potentially experience ovarian toxicity. So for the clinic we’re hoping that we’re going to get much more information about ovarian toxicity and its resolution as we continue to create more targeted therapies and improve survivorship over time. We’ll be able to have better information to counsel patients if we do a better job embedding these kinds of measures within all of our clinical trials.