Hot Flash Drug Works at Any Point in Breast Cancer Hormone Therapy

A drug for hot flashes reduced their severity and frequency in people taking endocrine therapy for breast cancer, no matter how long they had been on that therapy, according to a subgroup analysis of the phase 3 OASIS-4 trial presented at the 2026 ESMO Congress.

The trial tested Lynkuet (elinzanetant), a nonhormonal drug that blocks two receptors in the brain involved in body temperature control. In this analysis, researchers looked at whether the drug worked differently depending on whether patients had started endocrine therapy less than six months, six months to one year, one to two years or more than two years before. Lynkuet reduced hot flashes across all groups.

Lynkuet is approved by the Food and Drug Administration (FDA) to treat hot flashes caused by menopause, and the FDA is reviewing it for people with breast cancer who have hot flashes caused by endocrine therapy.

In an interview with CURE, Dr. Matteo Lambertini, director of the medical oncology department at Galliera Hospital in Genoa, Italy, and associate professor of medical oncology at the University of Genoa, discussed how hot flashes affect patients, what the findings show and what patients can ask their care team.

This interview has been edited for length and clarity.

CURE: How much do hot flashes affect patients’ quality of life and their willingness to stay on endocrine therapy?

Lambertini: Hot flashes are definitely one of the worst side effects of endocrine therapy. This is something we experience every day in clinical practice. With all the types of endocrine therapies that we have available, hot flashes are one of the most bothersome side effects, especially in premenopausal women, where we use endocrine therapies like ovarian function suppression plus an aromatase inhibitor or tamoxifen. A lot of patients experience these side effects.

When there is a side effect like that, we may encounter another very important problem from an oncology perspective, which is that the patient may just discontinue endocrine therapy. They can’t tolerate it, so they prefer to stop instead of continuing the treatment for [five to] 10 years. And suboptimal therapy can translate into suboptimal outcomes. So addressing side effects is important to improve the quality of life of our patients, but it’s also very important to help them stick to endocrine therapy and reduce as much as we can the risk of recurrence.

What has research shown about this drug for hot flashes in people taking endocrine therapy for breast cancer?

A year ago, we had a publication in the New England Journal of Medicine of a very important phase 3 trial of a new drug called elinzanetant. It targets two receptors in the brain, NK1 and NK3, that control thermoregulation, so they are important in the regulation of hot flashes. This trial in patients with breast cancer taking endocrine therapy showed that when this drug is given, there is a dramatic decrease in the severity and frequency of hot flashes, with a major improvement in side effect management.

What should patients struggling with hot flashes ask their care team about, especially if hormone-based options aren’t right for them?

The main strategy we have to control hot flashes is hormone-based therapy. But for patients with a history of breast cancer, we cannot offer hormones; otherwise, we are going to increase their risk of recurrence. So we need to find alternatives.

I start with what we call non-pharmacological approaches. These are simple approaches, but they can be very helpful to address different side effects of endocrine therapy, not only hot flashes. I’m talking, for example, about physical exercise, cognitive behavioral therapy, yoga and acupuncture.

We also have pharmacological strategies. For hot flashes specifically, some antidepressants, used at a lower dose than for depressive symptoms, seem to help. However, in my practice, it’s not very easy to prescribe these agents because they have other side effects, and patients already experiencing side effects from endocrine therapy are not really willing to take an antidepressant to manage this. So having this new class of non-hormone-based agents that are very effective in controlling this side effect is something all of us were really waiting for.

Did it matter how long patients had been on endocrine therapy?

At the ESMO 2026 Congress, we presented a subgroup analysis of the OASIS-4 trial, the trial that demonstrated the efficacy and safety of elinzanetant in reducing the burden of vasomotor symptoms. We looked at whether there was a different effect in patients who started the drug less than six months, six months to one year, one to two years or more than two years after starting endocrine therapy. The main take-home message is that elinzanetant significantly reduced the severity and frequency of hot flashes regardless of how long patients had been on endocrine therapy.

From a clinical perspective, this is very important, because some patients experience this side effect a few months after starting therapy, and others may experience it two or three years down the road. With this data, we are reassured that we can start whenever there is a need for the patient.

Is the drug safe to take with different types of endocrine therapy?

The side effect profile looks very manageable. We had some concern about a potential difference in efficacy according to the type of endocrine therapy. However, based on another secondary analysis of OASIS-4 presented at the 2026 ASCO Annual Meeting, the efficacy and safety were seen regardless of the type of endocrine therapy. The drug is effective and safe whether the patient is receiving tamoxifen or an aromatase inhibitor, and for premenopausal women, whether or not they are receiving ovarian function suppression.

The only safety concern we have is for patients taking a CDK4/6 inhibitor, for whom we don’t yet have specific data. We don’t have particular concern with abemaciclib [Verzenio]. We may have some concern with ribociclib [Kisqali], and because of the potential for liver toxicity, it is better not to combine ribociclib with elinzanetant.

Where does this drug fit alongside other options for hot flashes?

Non-pharmacological approaches should definitely be the first approach when we first see a patient experiencing these side effects. Cognitive behavioral therapy is a super effective treatment, also for other side effects of endocrine therapy, like fatigue and joint pain. We also have data with acupuncture and yoga. I also recommend physical exercise. It’s not really for vasomotor symptoms, but physical exercise has a lot of randomized data showing it helps improve quality of life and the management of other side effects of endocrine therapy.

Then, when we reassess the patient, if we didn’t see an optimal improvement, we should move to pharmacological agents. Based on the data from the OASIS-4 trial, I have no doubt this will be my first approach: it’s a non-hormonal agent with a very good toxicity profile and very strong data from a randomized trial in this specific patient population.

Could better control of hot flashes help patients stay on endocrine therapy?

We hope that with better side effect management, we are going to increase not only quality of life but also adherence to endocrine therapy. This was not assessed in the OASIS-4 trial, so I don’t have an answer from the trial. But this is definitely a very important question that we need to address.

We will probably soon have real-world studies looking at the effectiveness and safety of elinzanetant, and in these studies, we definitely need to look at adherence rates, because adherence is one of the most critical issues we have when we prescribe adjuvant endocrine therapy.

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