OASIS-4 Trial: Elinzanetant Reduces Frequency of Vasomotor Symptoms Related to Endocrine Therapy for HR-Positive Breast Cancer

Fatima Cardoso, MD

Photo courtesy of The Male Breast Cancer Alliance

Treatment with elinzanetant significantly reduced vasomotor symptoms (VMS) in women receiving endocrine therapy for hormone receptor (HR)-positive breast cancer, according to new results from the phase 3 OASIS-4 clinical trial.¹

Findings from the fourth study in the OASIS clinical trial program were presented at the American Society of Clinical Oncology (ASCO) Annual Meeting, held May 30 – June 3, 2025, in Chicago, and were simultaneously published in the New England Journal of Medicine (NEJM).

“Menopausal symptoms are frequent side effects of endocrine therapy for breast cancer, often leading to discontinuation, which is why management of these symptoms can play an important role in breast cancer treatment,” Fatima Cardoso, MD, Principal Investigator of OASIS-4, Champalimaud Foundation, Lisbon, Portugal, said in a press release. “With no currently approved treatments for this indication, there is an unmet medical need for therapeutic options.”²

Elinzanetant’s mechanism of action targets the kisspeptin–neurokinin–dynorphin (KNDy) neuron pathway implicated in estrogen-withdrawal–related thermoregulatory dysfunction. It is the first oral, once-daily dual NK-1/NK-3 antagonist in late-stage global development for VMS associated with both menopause and endocrine therapy.²

The multicenter, double-blind, placebo-controlled trial randomized 474 women aged 18 to 70 years across 90 international sites (excluding the US) to receive elinzanetant 120 mg once daily (n = 316) or placebo for 12 weeks followed by elinzanetant for 40 weeks (n = 158). Eligible participants were on endocrine therapy—either tamoxifen or aromatase inhibitors—with or without gonadotropin-releasing hormone analogues, and experiencing at least 35 moderate-to-severe VMS per week.¹

At baseline, the mean daily frequency of moderate-to-severe VMS was 11.4 episodes (95% CI, 10.7–12.2) in the elinzanetant group and 11.5 (95% CI, 10.5–12.5) in the placebo group. By week 4, the frequency decreased by −6.5 episodes (95% CI, −7.2 to −5.8) in the elinzanetant group and −3.0 episodes (95% CI, −3.9 to −2.2) in the placebo group (least-squares mean difference, −3.5; 95% CI, −4.4 to −2.6; P < .001). At week 12, the reductions were −7.8 (95% CI, −8.5 to −7.1) and −4.2 (95% CI, −5.2 to −3.2), respectively (least-squares mean difference, −3.4; 95% CI, −4.2 to −2.5; P < .001).¹

Key secondary endpoints also favored elinzanetant. From baseline to week 12, the PROMIS Sleep Disturbance Short Form 8b T score decreased by −10.6 points (95% CI, −11.5 to −9.6) with elinzanetant and −4.1 (95% CI, −5.3 to −2.9) with placebo (difference, −6.1 points; 95% CI, −7.5 to −4.8; P < .001). The MENQOL total score decreased by −1.3 (95% CI, −1.4 to −1.2) in the elinzanetant group vs −0.5 (95% CI, −0.7 to −0.3) in the placebo group (difference, −0.7; 95% CI, −0.9 to −0.5; P < .001).¹

Elinzanetant also showed benefit as early as week 1, reducing VMS frequency by −4.0 episodes (95% CI, −4.6 to −3.5) compared to −1.8 (95% CI, −2.4 to −1.2) with placebo. A ≥50% reduction in VMS was observed in 74.3% of patients receiving elinzanetant at week 12, compared to 35.8% with placebo.¹

In terms of safety, adverse events were common but mostly mild, investigators reported. During weeks 1–12, 69.8% of women in the elinzanetant group reported at least one adverse event, compared to 62.0% in the placebo group. The most frequently reported adverse events included headache, fatigue, and somnolence. Serious adverse events occurred in 8 women (2.5%) in the elinzanetant group and 1 woman (0.6%) in the placebo group.¹

Liver enzyme elevations meeting pre-specified criteria for close monitoring were observed in 5 women, all of whom recovered fully, and none met criteria for Hy’s law. The liver safety monitoring board concluded that these elevations did not indicate substantive hepatotoxicity associated with elinzanetant.¹

This trial offers promising evidence supporting elinzanetant as a potential therapeutic option for managing vasomotor symptoms in women undergoing endocrine therapy for breast cancer, a population for whom current options are limited. Further data from ongoing extensions and real-world studies are anticipated to better define its role in clinical practice.¹

“These results are consistent with the previously published phase 3 trials involving women with vasomotor symptoms caused by natural or surgically induced menopause, which shows the reproducibility of findings across populations,” investigators concluded.¹

Submissions for marketing authorizations for elinzanetant are ongoing in the US, EU, and other global markets. Further data from the OASIS program, including a 2-year extension phase, will inform long-term safety and real-world utility.²

References:

1. Cardoso F, Parke S, Brennan DJ ,et al. Elinzanetant for vasomotor symptoms from endocrine therapy for breast cancer. NEJM. Published online June 2, 2025. doi:10.1056/NEJMoa2415566

2. Elinzanetant significantly reduces frequency of moderate to severe vasomotor symptoms associated with endocrine therapy for breast cancer in Phase III OASIS-4 study. News release. Bayer. June 2, 2025. Accessed June 3, 2025. https://www.bayer.com/media/en-us/elinzanetant-significantly-reduces-frequency-of-moderate-to-severe-vasomotor-symptoms-associated-with-endocrine-therapy-for-breast-cancer-in-phase-iii-oasis-4-study/