Elinzanetant Significantly Reduces Vasomotor Symptoms in Women on Endocrine Therapy: NEJM
A recent study published in The New England Journal of Medicine has found that elinzanetant, a therapy targeted at neurokinin receptors, significantly reduces moderate-to-severe vasomotor symptoms in women on endocrine treatment for HR-positive breast cancer or its prevention. Vasomotor symptoms including classic hot flashes and night sweats, are among the most prevalent and distressing side effects of endocrine treatments such as tamoxifen or aromatase inhibitors. The study was conducted by Fatima C. and fellow researchers.
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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