The US Food and Drug Administration has expanded treatment options for adult with advanced breast cancerby granting accelerated approval to AstraZeneca’s Etcamah (camizestrant).
Etcamah, an oral tablet, is approved for use in combination with a CDK4/6 inhibitor (abemaciclib, palbociclib, or ribociclib) for the treatment of adult patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, locally advanced or metastatic breast cancer upon detection of estrogen receptor-1 (ESR1) mutation during aromatase inhibitor and CDK 4/6 inhibitor therapy, based on an FDA-authorised test.
ESR1 mutations are acquired resistance mutations that tumours can develop during treatment with an aromatase inhibitor, a type of endocrine therapy commonly used as a front-line treatment for locally advanced or metastatic breast cancer. At diagnosis of HR-positive metastatic breast cancer, fewer than 5 per cent of patients have this tumour mutation. Following disease progression on an aromatase inhibitor, nearly 40 per cent of patients may have an ESR1 mutation.
Acting FDA Commissioner Kyle Diamantas said the approval “delivers a win to these patients” by granting them a targeted therapy designed specifically to overcome resistance, giving them more time before their disease progresses.
“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, director of the FDA’s Oncology Center of Excellence. However, he said additional evidence is needed to confirm clinical benefit.
The accelerated approval was based on results from the pivotal SERENA-6 Phase III trial, which showed Etcamah in combination with a CDK4/6 inhibitor reduced the risk of disease progression or death by 56% versus standard-of-care treatment with an aromatase inhibitor (anastrozole or letrozole) in combination with a CDK4/6 inhibitor in patients with an emergent ESR1 tumour mutation.
The estimated median progression-free survival was 16 months in the Etcamah plus CDK4/6 inhibitor arm, compared with 9.2 months in the aromatase inhibitor plus CDK4/6 inhibitor arm.
According to Dave Fredrickson, executive vice president, Oncology Haematology Business Unit, AstraZeneca, this is the tenth FDA approval across AstraZeneca’s portfolio this year and the fourth in breast cancer.
“The Etcamah combination reflects AstraZeneca’s leadership in redefining breast cancer care by pioneering a new approach using circulating tumour DNA and is the first and only medicine of its type in the 1st-line setting,” Fredrickson said.
Etcamah is also approved in more than 30 countries across the globe, including the European Union, Japan, Canada and the UK, based on results from the SERENA-6 Phase III trial.
The FDA also approved a companion diagnostic test to detect emerging ESR1 resistance mutations in the circulating tumour DNA (ctDNA) of patients with HR-positive, HER2-negative advanced or metastatic breast cancer.
