Orserdu Approval for Metastatic Breast Cancer Represents ‘Big Breakthrough’

The recent Food and Drug Administration approval of Orserdu (elacestrant) for some patients with metastatic breast cancer fulfills an unmet need and represents an exciting option in the space, according to an expert.

The approval is indicated for patients who have metastatic HER-2 negative, ER-positive breast cancer, who have already had a prior endocrine therapy and whose tumor has an ESR-1 mutation. It came based off results from the EMERALD trial, which demonstrated a median progression-free survival (time during and after treatment when the patient lives without disease progression) of 3.8 months with Orserdu and 1.9 months with fulvestrant or another aromatase inhibitor in patients with ESR1 mutations (228 patients).

“For patients who have metastatic hormone-receptor positive breast cancer, it's really exciting to see that now after actually several decades, we finally have a new approval for an endocrine therapy,” said Dr. Sara M. Tolaney, a breast medical oncologist and chief of the division of breast oncology at Dana Farber Cancer Institute in Boston, in an interview with CURE®.

She explained that endocrine therapies are available for this population, but unfortunately, after a while, they stop working so a new one was needed.

And Orserdu falls into a class of drugs called a selective estrogen receptor degrader. Prior to this approval there was only one other available — Faslodex (fulvestrant), however that drug is given as a shot in the butt, which Tolaney said “is not terribly comfortable for the patients to endure.” Another problem is because of the way it is formulated, Faslodex doesn’t enter the system as easily as an oral drug, such as Orserdu, would.

“So we've been awaiting development of oral drugs that would be have better bioavailability, for example, than the injected version, and potentially could work even better than that injected version,” she added. “I think having a drug that works better than (Faslodex), and, again, doesn't put patients through that injection, is really filling an unmet need in that setting.”

Enter Orserdu. It particularly showed improvement in patients with an ESR1 mutation, which is important because most endocrine therapies do not work well in these patients, Tolaney noted, and many of them have already progressed on prior lines of therapy.

“I think patients are really going to be excited to have this opportunity,” she said. “One, because it can work better than (Faslodex) if their tumors have an ESR1 mutation, but two, because it's also oral. So, I think it’s really nice for patients in terms of quality of life — also very meaningful.”

Tolaney noted Orserdu was also very well tolerated in patients. The most common side effects, occurring in at least 10% of patients, included musculoskeletal pain, nausea, increased cholesterol, increased AST, increased triglycerides (fat lipid in blood), fatigue, decreased hemoglobin, vomiting, increased ALT, decreased sodium, increased creatinine, decreased appetite, diarrhea, headache, constipation, abdominal pain, hot flush and dyspepsia.

Overall, this is an exciting approval for this patient population, Tolaney said, as they have been waiting to overcome the challenge of dealing with injecting the only other option and there is still more to come.

“As a physician who treats a lot of patients who have hormone receptor positive breast cancer, I think this has been really exciting. Because again, dealing with the injections for patients is challenging, and we've been wanting to have endocrine drugs that work even better than agents that we have available,” she concluded. “I think this is just the beginning though of a road of hopefully, multiple new anti-estrogen drugs that hopefully will come in the future. … I think it's an exciting time because, again, it's been decades since we've had a new endocrine pill. And so this is this is really a very big breakthrough in breast cancer.”

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