Nirogacestat Shows Promise With Manageable Fertility Concerns in Young Women


Elizabeth Logers, MD, PhD, discusses the implications of ovarian toxicity on female patients of reproductive age being treated with nirogacestat for desmoid tumors.

This study presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting investigated the impact of nirogacestat (Ogsiveo) on ovarian function in young women with desmoid tumors. The study found that 75% of women treated with nirogacestat experienced ovarian toxicity, which could potentially affect their fertility.

However, in most cases, the ovarian toxicity was temporary. When women stopped taking the drug, their ovarian function typically returned to normal. This suggests that nirogacestat may still be a viable treatment option for some women, as long as they are aware of the potential adverse effects.

The study also highlights the importance of monitoring ovarian function during cancer treatment, especially for young women who may want to have children in the future. There is currently no standard approach for monitoring ovarian toxicity, but this study suggests that a combination of hormone tests and symptom tracking could be helpful.

Here Elizabeth Loggers, MD, PhD, presenter of the study and associate professor in the Clinical Research Division at Fred Hutch Cancer Center, discusses the study's findings and implications.


0:05 | There are approximately 1.4 million females under the age of 45 who will be diagnosed with cancer annually. And here in the United States, there are approximately 45,000 fertile females. And so this topic is important because the incidence of early onset cancers is increasing in our fertile populations. And our treatments are getting better, and so people are going to live longer, and ovarian toxicity is going to be more important. So investigators need to start paying more attention to this. And we need to do a better job collecting data.

0:38 | One of the ways that we tried to demonstrate the importance of this was by focusing on the results from the device study, which was a phase 3 study of nirogacestate, which is an oral gamma secretase inhibitor used in desmoid tumors. And over the course of that trial, we learned that ovarian toxicity was a safety signal, and therefore needed to do more in depth study of toxicity and its resolution. And so, for example, in that study, we saw that 75% of females of reproductive potential actually experienced ovarian toxicity. We learned through this process of measuring ovarian toxicity and assessing its resolution that 78% of those women were going to have the resolution of that toxicity. And of those, 100% would resolve once they stopped the treatment for any reason. And then 71% actually had resolution of their ovarian toxicity still on treatment. So it's an interesting story. And it teaches us to be more consistent in the way that we measure ovarian toxicity.

1:42 | One of the key points of this abstract was to highlight ASCO's clear recommendations in this area. ASCO had 3 primary recommendations. The first was to include measures of ovarian toxicity all clinical trials. They recommend to doing that at baseline and at 12 to 24 months after completion of the trial. And then to include both clinical measures like menstrual diaries, as well as hormonal measures like anti-Mullerian hormone and other things that help us assess the toxicity. So I think it's just important that clinical trial lists begin to incorporate these measures in the early design of their studies to ensure that this is done in an efficient and an effective way, so that we can use that information when we're counseling patients in the future.

Transcription created with AI and edited for clarity.

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