FDA Grants Priority Review to Elinzanetant for Hot Flashes Caused by Breast Cancer Endocrine Therapy
核心洞察
The FDA accepted Bayer (搜索)'s supplemental new drug application for elinzanetant and granted priority review for moderate to severe vasomotor symptoms (搜索) tied to endocrine therapy in HR-positive breast cancer (搜索).
The filing rests on the phase 3 OASIS-4 trial, in which 474 women on adjuvant endocrine therapy had statistically significant reductions in daily hot flash frequency at weeks 4 and 12 versus placebo.
No FDA-approved pharmacologic option currently exists for this indication in the US, and hot flashes are a leading cause of early endocrine therapy discontinuation.
The FDA has accepted Bayer (搜索)'s supplemental new drug application for elinzanetant (Lynkuet (搜索)) and granted it priority review for moderate to severe vasomotor symptoms (搜索) (VMS) in women receiving endocrine therapy for hormone receptor-positive (HR+) breast cancer, the company announced on Sept. 28, 2026. The designation applies to treatment or prevention settings of HR+ disease. Priority review means the agency has agreed to a faster-than-usual decision timeline; it is not an approval.
The action identifies the application as addressing an unmet medical need. No pharmacologic option is currently FDA-approved for this indication in the United States.
"Currently, there are no FDA approved treatment options for moderate to severe vasomotor symptoms (搜索) associated with endocrine therapy in patients with HR+ breast cancer in the U.S. This treatment gap underscores an important unmet medical need for this population," Kristie Baisden, DO, vice president of US medical affairs for women's health at Bayer (搜索), said in a press release.
OASIS-4 Trial Design
The submission is supported by OASIS-4 (NCT05587296), a 52-week, randomized, double-blind, placebo-controlled phase 3 study conducted at 90 sites outside the United States. It enrolled 474 women aged 18 to 70 with moderate to severe VMS associated with adjuvant endocrine therapy (AET) for HR+ breast cancer or its prevention.
Participants were randomized 2:1 to elinzanetant 120 mg once daily for the full 52 weeks (n = 316) or to once-daily placebo for 12 weeks followed by elinzanetant 120 mg once daily for 40 weeks (n = 158). The coprimary endpoints tracked change in average daily frequency of moderate to severe VMS from baseline to week 4 and from baseline to week 12.
Baseline symptom burden was similar between arms: a mean of 11.4 daily episodes (95% CI, 10.7-12.2) in the elinzanetant group and 11.5 (95% CI, 10.5-12.5) in the placebo group.
Efficacy Results
By week 4, daily VMS frequency fell by a mean of 6.5 episodes (95% CI, -7.2 to -5.8) with elinzanetant versus 3.0 episodes (95% CI, -3.9 to -2.2) with placebo, a least-squares mean difference of -3.5 episodes (95% CI, -4.4 to -2.6; P < .001). By week 12, the reduction reached 7.8 episodes (95% CI, -8.5 to -7.1) with elinzanetant versus 4.2 episodes (95% CI, -5.2 to -3.2) with placebo (least-squares mean difference, -3.4 episodes; 95% CI, -4.2 to -2.5; P < .001).
All key secondary endpoints were also met. VMS severity declined at weeks 4 and 12, event frequency dropped by week 1, and sleep quality and menopause-related quality of life improved relative to placebo by week 12, with benefits persisting for the remainder of the study. Findings were presented at the 2025 American Society of Clinical Oncology Annual Meeting and published in The New England Journal of Medicine.
A 2026 analysis found lasting relief regardless of whether women took tamoxifen or an aromatase inhibitor (搜索). At the end of the one-year trial, 91.6% of participants chose to continue treatment for another two years.
Safety Profile
Across the first 12 weeks, 220 patients in the elinzanetant group (69.8%) and 98 in the placebo group (62.0%) experienced at least one adverse event while on study drug or placebo. Headache, fatigue and somnolence were reported most often. Somnolence occurred in about 11% of women on elinzanetant, headache and fatigue in about 10% each, and joint pain and nausea in about 6% each. Diarrhea was also reported more frequently with elinzanetant than placebo during the controlled period.
Serious adverse events during the first 12 weeks were uncommon but more frequent with elinzanetant, affecting 8 patients (2.5%) versus 1 patient (0.6%) on placebo. Over a full year, researchers reported the drug remained well tolerated, and a two-year extension study is still collecting safety data. For the current menopause approval, the FDA recommends liver blood tests before starting elinzanetant and again at three months.
Mechanism and Regulatory History
Elinzanetant is a once-daily oral, nonhormonal dual antagonist of the NK-1 and NK-3 neurokinin receptors, which are implicated in thermoregulatory signaling pathways in the hypothalamus. When estrogen falls, whether from menopause or endocrine therapy, that temperature-regulating center can misfire and trigger hot flashes. Because most women with HR+ breast cancer are advised to avoid hormone therapy, a nonhormonal option matters.
The FDA first approved elinzanetant in October 2025 for moderate to severe VMS due to menopause, based on the phase 3 OASIS-1, OASIS-2 and OASIS-3 trials (NCT05042362, NCT05099159, NCT05030584), conducted in 1,420 women. OASIS-1 and OASIS-2 established efficacy on coprimary endpoints of VMS frequency and severity at weeks 4 and 12; OASIS-3 evaluated long-term safety over 52 weeks.
Outside the United States, elinzanetant became the first agent approved specifically for adjuvant endocrine therapy-related VMS in breast cancer in the United Kingdom, Switzerland and Canada, with Health Canada approval in August 2026. The European Union approved it for both uses in November 2025. A 2026 NCCN survivorship guideline update named elinzanetant a preferred nonhormonal option among NK-1/NK-3 antagonists for moderate to severe VMS stemming from medically or surgically induced menopause.
Clinical Context
Breast cancer accounts for approximately 30% of all cancers diagnosed in women in the United States, with HR+ subtypes comprising roughly 70% of cases. ASCO guidelines recommend endocrine therapy as standard adjuvant treatment for HR+ breast cancer, with a minimum recommended duration of 5 years and potential extension to 10 years depending on disease characteristics and individual risk factors. Hot flashes are among the most commonly reported adverse effects of endocrine therapy and a leading cause of early treatment discontinuation, a clinically significant concern given the survival benefit associated with completing the full course.
"Endocrine therapy is a standard of care for many women facing HR+ breast cancer, which can commonly cause adverse events such as vasomotor symptoms (搜索)," said Fatima Cardoso, MD, FESMO, OASIS-4 primary investigator, director of the breast unit at Centre Antoine Lacassagne and a member of the Advanced Breast Cancer Global Alliance, in Nice, France. "It's important that we continue to learn more about vasomotor symptoms due to endocrine therapy as part of supporting women throughout their breast cancer care journey."
"The positive results from the OASIS-4 study further support the potential of elinzanetant to address unmet needs in menopause care, including for women facing VMS associated with breast cancer treatment," said Cecilia Caetano, MD, vice president of global medical affairs and evidence generation lead for women's health at Bayer (搜索) Pharmaceuticals Division.
Open Questions
Priority review signals the FDA's assessment of potential clinical benefit but does not guarantee approval, and the benefit-risk profile will be evaluated through the full review process. OASIS-4 was conducted entirely outside the United States, which may raise questions about generalizability to US patient populations. The placebo-controlled period was limited to 12 weeks, and long-term comparative safety data against active comparators such as selective serotonin reuptake inhibitors or serotonin-norepinephrine reuptake inhibitors, commonly used off-label for VMS in this setting, were not reported. Whether symptom reduction in OASIS-4 translates to improved endocrine therapy adherence or downstream survival outcomes remains to be established.
For patients whose hot flashes threaten adherence, clinicians already have options to discuss, including certain antidepressants, gabapentin and nonmedication approaches such as cognitive behavioral therapy.