Enhertu moves into frontline breast cancer treatment
Daiichi Sankyo and AstraZeneca's Enhertu has been cleared for previously-untreated HER2-positive breast cancer in the US, becoming the first new first-line option in more than a decade.
The FDA approval of Enhertu (trastuzumab deruxtecan) in combination with Roche's Perjeta (pertuzumab) is for patients with advanced-stage tumours that cannot be treated with surgery or have spread to other parts of the body and have a HER2 score of 3 or more on immunohistochemistry testing.
It follows the results of the DESTINY-Breast09 study, reported at ASCO this year, which found that Enhertu/Perjeta achieved a 44% reduction in progression-free survival (PFS) compared to the widely used THP regimen of Perjeta, trastuzumab, and taxane chemotherapy.
Patients taking the Enhertu regimen achieved a median PFS of more than three years (40.7 months), compared to just over two years (26.9 months) with THP, which was accompanied by a trend towards improved overall survival (OS).
Principal study investigator Sara Tolaney of the Dana-Farber Cancer Institute said that, given treatment-naïve patients with HER2-positive metastatic breast cancer often experience disease progression around two years after starting treatment, the result means that Enhertu and Perjeta "should become a new first-line standard of care in this setting."
Enhertu is associated with an increased rate of interstitial lung disease (ILD), which was seen in around 12% of patients, but in most cases was manageable and not severe.
The study is also comparing anti-HER2 antibody-drug conjugate (ADC) Enhertu as a monotherapy against THP, but so far, the data have not revealed any benefit over the comparator arm.
Enhertu is already approved as a second-line or later treatment for HER2-positive breast cancer, along with other indications, including HR-positive, HER2-low and ultralow breast cancer, and is a major growth driver for both AZ and Daiichi Sankyo.
Combined sales of the drug amounted to $3.58 billion in the first nine months of this year, a 31% increase on the same period of 2024, which puts it on course to achieve its 2025 sales expectation of $5 billion or more.
AZ and Daiichi Sankyo are also looking to move Enhertu into earlier-stage HER2-positive breast cancer, and have taken a major step forward in that effort with the results of the DESTINY-Breast05 and DESTINY-Breast11 studies, focusing on 'post-neoadjuvant' and neoadjuvant settings, respectively. Those studies will now form the basis of regulatory filings, according to the partners.
