Elinzanetant Significantly Reduces Vasomotor Symptoms in Women on Endocrine Therapy: NEJM

Endocrine therapy is an ongoing cornerstone for breast cancer treatment and prevention in HR-positive disease, especially for premenopausal and early postmenopausal women.Vasomotor symptoms (VMS) such as hot flashes, however, may have a significant influence on treatment compliance and tolerance. Elinzanetant, a selective dual neurokinin-1 and neurokinin-3 receptor antagonist, had been previously demonstrated to be efficacious for the alleviation of menopausal hot flashes. This study extends that data by assessing its activity in women receiving endocrine therapy, a group in which hormone treatments for VMS are contraindicated due to cancer risk.

Phase 3 double-blind, randomized, placebo-controlled trial recruited women 18 to 70 years with moderate-to-severe VMS related to endocrine therapy for HR-positive breast cancer or prevention. They were randomly allocated in a 2:1 ratio to receive:

• Elinzanetant 120 mg daily for 52 weeks (316 participants)

• Placebo daily for 12 weeks and then elinzanetant for 40 weeks (158 participants)

The main endpoints were changes from baseline in the mean number of daily moderate-to-severe VMS at weeks 4 and 12. Safety, including adverse effects and serious adverse effects, was monitored closely as well.

Key Findings

Baseline VMS frequency:

• 11.4 episodes/day (95% CI, 10.7–12.2) with elinzanetant

• 11.5 episodes/day (95% CI, 10.5–12.5) with placebo

Week 4 results:

• Mean reduction in VMS: −6.5 episodes with elinzanetant vs. −3.0 episodes with placebo

• Least-squares mean difference: −3.5 episodes (95% CI, −4.4 to −2.6; P < 0.001)

Week 12 results:

• Mean decrease in VMS: −7.8 episodes with elinzanetant versus −4.2 episodes with placebo

• Least-squares mean difference: −3.4 episodes (95% CI, −4.2 to −2.5; P < 0.001)

Adverse Events (Weeks 1–12):

• 220 participants (69.8%) on elinzanetant experienced ≥1 adverse event

• 98 participants (62.0%) on placebo experienced ≥1 adverse event

• Most frequent: headache, fatigue, and somnolence

Serious adverse events:

•8 participants (2.5%) on elinzanetant

• 1 placebo participant (0.6%)

This substantial, phase 3 trial demonstrates that elinzanetant reduces substantially the rate of vasomoter symptoms among women treated with endocrine therapy for HR-positive breast cancer or its prevention. These findings indicate that elinzanetant may become an essential component of quality of life and adherence-enhancing breast cancer treatment and prevention strategies.

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