FDA overrides adcomm and approves AZ's oral SERD

The FDA has gone against the advice of its own expert advisors and approved AstraZeneca's Etcamah as a frontline treatment for breast cancer.

Oral selective oestrogen receptor degrader (SERD) Etcamah (camizestrant) has been cleared in the US for use in combination with a CDK4/6 inhibitor as a first-line treatment for locally advanced or metastatic HR-positive, HER2-negative breast cancer with a mutation in the ESR1 gene.

The decision came after the FDA's Oncologic Drugs Advisory Committee (ODAC) voted in May that data from the pivotal SERENA-6 trial supporting AZ's marketing application for Etcamah was not strong enough to support approval. Shortly afterwards, the FDA extended its review by three months.

Since then, Etcamah has also been approved in Europe, Canada, Japan, and other markets, and the US decision now boosts AZ's hopes of hitting its peak sales target of around $5 billion a year for the drug. It is part of a portfolio of 20 new medicines that the company hopes will catapult sales above the $80 billion threshold by the end of the decade.

Etcamah is the first oral SERD to be approved as a first-line option for this form of breast cancer, said AZ, which said the new regimen has the potential to "reshape [the] treatment paradigm" for patients.

There are currently two approved drugs in the oral SERD class, namely Menarini/Stemline's Orserdu (elacestrant) and Eli Lilly's Inluriyo (imlunestrant), which are both approved for second-line use in patients with ESR1-mutated, HR-positive, HER2-negative advanced breast cancer.

The SERENA-6 trial showed that the combination of Etcamah and a CDK 4/6 drug reduced the risk of disease progression or death by 56% in patients with an emergent ESR1 tumour mutation, which suggests that the disease has started to become resistant to hormonal treatment.

The trial also showed a 37% improvement in the time to second disease progression, with a median progression-free survival of 16 months for the Etcamah regimen versus 9.2 months for the control therapy, as well as a trend towards improved overall survival.

"This marks the first FDA approval of a cancer therapy guided by the detection of a resistance mutation in circulating tumour DNA (ctDNA) before imaging tests show that the disease is progressing," said Angelo de Claro, who heads the FDA's cancer unit.

He added that while additional evidence is needed to confirm clinical benefit, "I commend both the FDA and the sponsor for their commitment to advancing cancer care and securing this accelerated approval."

The FDA also approved a companion diagnostic test developed by Guardant to detect emerging ESR1 resistance mutations in ctDNA, Guardant360 CDx, to support the rollout of Etcamah in this indication.