First patient dosed in trial evaluating fezolinetant for VMS in breast cancer patients

First patient dosed in trial evaluating fezolinetant for VMS in breast cancer patients | Image Credit: © Iryna - © Iryna - stock.adobe.com.

The first patient has received dosing in the phase 3 HIGHLIGHT 1 clinical trial evaluating the use of fezolinetant (VEOZAH; Astellas Pharma Inc) to treat moderate to severe vasomotor symptoms (VMS) in breast cancer patients with adjuvant endocrine therapy.¹

Approximately 2.2 million new breast cancer cases were reported in 2022, making it the most common cancer in women worldwide. Endocrine therapies used to treat breast cancer are associated with VMS, also known as hot flashes and night sweats.

The ability to use adjuvant endocrine therapies for breast cancer treatment is reported in approximately 77% of breast cancer patients, with up to 97% experiencing VMS. Fezolinetant was developed to manage moderate to severe VMS in breast cancer patients with adjuvant endocrine therapy through an oral, nonhormonal method.

Fezolinetant reduces the frequency and severity of VMS by blocking neurokinin B binding on the kisspeptin/neurokinin/dynorphin neuron, improving balance in the brain’s temperature control center.Currently, safety and efficacy data for fezolinetant in breast cancer patients with moderate to severe VMS is not well-established.

The safety and efficacy of fezolinetant are being evaluated in HIGHLIGHT 1, a randomized, placebo-controlled, double-blind trial. Participant include women receiving adjuvant endocrine therapies to treat stage 0 to stage 3 breast cancer experiencing moderate to severe VMS.

There are 540 participants planned for inclusion in the analysis, randomized 1:1 to receive fezolinetant or placebo across up to 100 sites worldwide. The change in moderate to severe VMS frequency and severity from baseline to weeks 4 and 12 are the coprimary endpoints of the analysis, with a final evaluation following 52 weeks of treatment at 55 weeks.

Positive safety and efficacy data was initially reported for fezolinetant against moderate to severe VMS in the phase 3b DAYLIGHT clinical trial.² In the DAYLIGHT trial, the safety in efficacy of fezolinetant was evaluated in menopausal women aged 40 to 65 years where hormone therapy was not recommended to treat moderate to severe VMS.

The study included 450 women across 69 different sites in Turkey, Canada, and Europe. These participants received either fezolinetant 45 mg or placebo once per day for 24 weeks, with a reduction in moderate to severe VMS between baseline and week 24 evaluated as the primary outcome.

In the DAYLIGHT study, serious treatment-emergent adverse events (TEAEs) were reported in under 5% of patients receiving fezolinetant. Headache and COVID-19 were commonly reported TEAEs.

Comorbidities reported for fezolinetant included severe kidney condition or kidney failure, cirrhosis, and taking CYP1A2 inhibitors. Increased liver blood test problems were reported as a potential severe side effect linked to fezolinetant use.

Liver problems include vomiting, nausea, jaundice, and abdomen pain. Other adverse events associated with fezolinetant include insomnia, back pain, hot flashes, and diarrhea.

Additional trials evaluating fezolinetant include the SKYLIGHT 1 and SKYLIGHT 2 pivotal trials. Over 1000 patients with moderate to severe VMS participated in these studies, encompassing a 12-week placebo period and 40-week extension period. Across these studies, fezolinetant has been indicated as safe and effective against moderate to severe VMS.

References

1. Astellas Initiates Phase 3 Clinical Study of Fezolinetant for VMS in Women with Breast Cancer Receiving Adjuvant Endocrine Therapy. Astellas Pharma Inc. August 27, 2024. Accessed August 27, 2024. https://www.prnewswire.com/news-releases/astellas-initiates-phase-3-clinical-study-of-fezolinetant-for-vms-in-women-with-breast-cancer-receiving-adjuvant-endocrine-therapy-302231193.html
2. Krewson C. Phase 3b study: Fezolinetant safe, effective for vasomotor symptoms. June 28, 2023, Accessed August 28, 2024. https://www.contemporaryobgyn.net/view/phase-3b-study-fezolinetant-safe-effective-for-vasomotor-symptoms