Members of the FDA’s Oncologic Drugs Advisory Committee questioned the design of AstraZeneca’s Phase 3 trial of camizestrant, which involved switching treatments at the point of mutation detection, as opposed to the current practice of changing regimens upon disease progression.
A panel of independent advisors have recommended against approving AstraZeneca’s oral SERD drug camizestrant for certain breast cancer patients alongside a CDK4/6 inhibitor.
The issue, the panelists contended, lies with AstraZeneca’s study design. In the Phase 3 SERENA-6 trial, the pharma opted to switch patients to camizestrant or continue their current treatment schedules at the point of testing for mutations in the ESR1 gene. This is an early point to switch treatment, which usually happens upon disease progression.
The committee members worried that an approval could set a precedent for other drugmakers, prompting similar trial designs without necessarily having robust evidence that an earlier switch indeed results in survival gains.
“The data for changing the paradigm just isn’t there,” Stanley Lipkowitz, deputy director of the center for cancer research at the National Cancer Institute, said when explaining his ‘no’ vote.
“I do agree with the FDA’s concern that all the next trials will do exactly this with no evidence that it’s improving outcomes,” he continued. While noting that he is “very excited” about oral SERDs, he couldn’t “say that we should change fundamentally how we approach patients based on this data.”
“If there were an OS [overall survival] benefit, I would have voted yes,” Lipkowitz said.
Six of the outside experts voted against AstraZeneca, versus three that came down in support of approval. The panelists were asked to vote on whether camizestrant demonstrated a clinically meaningful benefit in patients who have HR+/HER2- metastatic breast cancer with an ESR1 mutation.
For Natalie Compagni Portis, the patient representative on the panel, her ‘no’ vote leaned more heavily on the lack of survival data, which she said could weigh heavily on the psychology of women with breast cancer. “I think it’s an exciting possibility that we could truly change the paradigm and be able to truly assure patients that treating earlier means either living better and/or living longer with metastatic breast cancer.
“But I really wonder if we are exploiting the hope of women with metastatic breast cancer,” she continued. “Without evidence of longer overall survival and . . . to have very sparse data on [quality of life], it really seems only speculation and hope.”
SERENA-6 showed that patients treated with the camizestrant regimen saw a 56% reduction in the risk of disease progression or death, according to data published in June 2025 in The New England Journal of Medicine. OS data remain immature.
“Importantly, the panelists expressed enthusiasm for the potential of biomarker technology and did not question cami’s underlying activity, but were unconvinced by the trial meriting a change in the treatment paradigm,” Leerink Partners wrote in a Thursday evening note. “The panelists’ concerns were focused on the trial design, its endpoints, and its ability to establish clinical benefit. This leaves the door open for other cami programs.”
AstraZeneca is developing camizestrant in several other treatment settings for breast cancer, including for frontline care.
The FDA raised similar concerns as its outside experts. In a briefing document published earlier this week, internal reviewers pointed out that “the treatment paradigm evaluated in SERENA-6 is new.”
“Currently, no drugs have FDA approval for switching treatment in patients based on detection” as opposed to at radiographic progression, the agency documents read. “It is unclear whether changing treatment at this earlier timepoint, prior to radiographic progression, results in long-term benefit.”
The FDA does not have to follow the advice of an adcomm, but typically aligns with the experts’ recommendations.
