Elinzanetant Eases Vasomotor Symptoms In Breast Cancer Trial

Key Takeaways

• Larger reductions in symptom frequency than placebo were observed at both prespecified primary time points, weeks 4 and 12.
• The randomized phase 3 trial enrolled women 18 to 70 years old and used 2:1 assignment to elinzanetant or placebo followed by elinzanetant.
• During weeks 1 through 12, adverse events were more common with elinzanetant, and serious adverse events were uncommon in both groups.

In a phase 3 NEJM trial, elinzanetant was associated with a larger week 4 reduction in moderate-to-severe vasomotor symptoms than placebo among women receiving endocrine therapy, with a between-group least-squares mean difference of −3.5 episodes per day. Participants had symptoms associated with endocrine therapy for HR-positive breast cancer or its prevention among women at high risk for breast cancer. The randomized placebo-controlled comparison favored elinzanetant at this prespecified early efficacy assessment.

The phase 3 randomized, placebo-controlled trial enrolled women 18 to 70 years old with moderate-to-severe vasomotor symptoms linked to endocrine therapy for HR-positive breast cancer or its prevention among women at high risk for breast cancer. Investigators assigned 316 participants to elinzanetant and 158 to placebo–elinzanetant, with placebo followed by elinzanetant after 12 weeks. Elinzanetant was given at 120 mg once daily for 52 weeks. The primary endpoints were changes from baseline in mean daily symptom frequency at weeks 4 and 12. Baseline means were similar between groups at 11.4 and 11.5 episodes per day, respectively.

At week 4, mean daily symptom frequency declined by 6.5 episodes with elinzanetant and 3.0 with placebo, for a least-squares mean difference of −3.5 episodes (95% CI, −4.4 to −2.6; P<0.001). At week 12, the corresponding changes were −7.8 and −4.2 episodes per day. The least-squares mean difference at week 12 was −3.4 episodes, with a 95% CI of −4.2 to −2.5 and P<0.001. These findings supported the investigators’ conclusion that elinzanetant was associated with a lower frequency of endocrine therapy–associated vasomotor symptoms than placebo.

During weeks 1 through 12, adverse events occurred in 69.8% of participants receiving elinzanetant and 62.0% receiving placebo. Headache, fatigue, and somnolence were the most common events in the randomized period. Serious adverse events occurred in 2.5% of elinzanetant recipients, or 8 participants, and 0.6% of placebo recipients, or 1 participant. Serious adverse events were uncommon in both groups during the initial 12-week randomized interval.