With new data, Lilly sets pace for next wave of breast cancer drugs

An experimental breast cancer drug developed by Eli Lilly met its main goal in a Phase 3 study, helping people with a form of HER2-negative, ER-positive disease stay alive and progression free for longer than standard hormone-suppressing therapies, according to data disclosed Wednesday.

When combined with Lilly’s approved medicine Verezenio, the experimental drug, called imlunestrant, also helped women stay alive and progression free longer than treatment with imlunestrant alone regardless of their mutation status, according to results of the EMBER-3 trial presented at the San Antonio Breast Cancer Symposium. The data were also published in The New England Journal of Medicine.

Lilly conducted the trial in people with breast cancer who progressed following treatment with estrogen-suppressing drugs, some of whom also received Verezenio or another drug from its class. The primary goal was to show that imlunestrant could delay progression or death in those with a mutation called ESR1, which can make cancer resistant to hormone treatments.

“The median progression free survival observed in EMBER-3 is among the most compelling we’ve seen in [the trial population] and indicates a potential shift in the therapy options we provide for these patients, which are currently very limited,” said Komal Jhaveri, an endocrine therapy researcher at Memorial Sloan Kettering Cancer Center who helped lead the trial, in a statement provided by Lilly.

Imlunestrant comes from a next-generation class of hormone-modulating drugs that are meant to overcome resistance, particularly arising from ESR1 mutations. Oserdu, a drug from the same class, gained approval nearly two years ago for the same setting that Lilly targeted with imlunestrant in its study.

The class of drugs is called selective estrogen receptor degraders, or SERDs. A SERD called fulvestrant has been on the market for more than 20 years, but isn’t effective as an oral drug, and as an injection into the muscle takes weeks to reach peak blood concentrations, which limits its effectiveness.

The newer SERDs are intended to be taken orally, as well as provide a stronger and more consistent biological effect. Besides Lilly and Menarini, which markets Oserdu, AstraZeneca, Roche and Arvinas are advancing drugs in this class.

In EMBER-3, Lilly enrolled 874 people with breast cancer, and randomized them into groups that received imlunestrant; imlunestrant and Verezenio; or standard of care, which was either fulvestrant or another drug called exemestane, although most got fulvestrant.

Imlunestrant alone reduced the risk of progression or death by 38% in those with the ESR1 mutations, compared with the standard of care, offering a 1.7 month benefit in the median time to progression or death. In a larger group that included those with the mutation and those without, imlunestrant alone didn’t have a statistically significant benefit.

Imlunestrant plus Verezenio reduced the risk of progression or death by 43% in that larger group, which included people whose tumors were both ESR1 positive and negative, over imlunestrant alone. That represented a 3.9 month benefit in median time to death or progression.

Side effects were similar in the imlunestrant and standard of care arms, but the combination of Verezenio and imlunestrant had higher rates of many side effects including nausea, anemia, and suppressed white blood cell counts. The combination also had more “Grade 3” or higher adverse events, indicating cases that were judged to be severe and potentially requiring urgent medical care.

More than half of those receiving imlunestrant alone or in combination interrupted their treatment because of side effects, while 39% reduced their doses and 6% discontinued treatment altogether. Trial investigators also reported three deaths they believed were related to treatment.

The trial didn’t statistically compare the combination treatment to the standard of care. But a Lilly spokesperson said the benefit is “highly clinically meaningful for this population in need of more effective endocrine-based therapies,” and will be attractive to physicians and patients.

Oral SERDs have had a rocky path to the market, with Sanofi scrapping one after a failed Phase 3 trial and Roche dealing with setbacks to its experimental drug.

However, AstraZeneca is expecting results next year from a trial that tests its SERD with drugs from Verzenio’s class against drugs from Verzenio’s class in combination with another type of breast cancer treatment called an aromatase inhibitor.

Arvinas, with its partner Pfizer, meanwhile, are also expecting data in early 2025 from a trial testing its SERD against fulvestrant.

This post has been syndicated from a third-party source. View the original article here.