Enhertu poised to move first line in HER2+ breast cancer
AstraZeneca and Daiichi Sankyo are preparing regulatory filings that could make their HER2-directed antibody-drug conjugate (ADC) Enhertu an option for previously untreated breast cancer for the first time.
The results of the phase 3 DESTINY-Breast09 study will form the backbone of that effort, after showing that the combination of Enhertu (trastuzumab deruxtecan) with Roche's anti-HER2 antibody Perjeta (pertuzumab) was better at extending the time to cancer progression or death in patients with HER2-positive breast cancer than the go-to regimen of a taxane, trastuzumab, and pertuzumab (THP).
The improvement in progression-free survival (PFS) was seen across a broad spectrum of patients in the study and marks the first time in more than a decade that a regimen has improved on standard first-line care for this type of breast cancer, according to the two drugmakers. There was also a trend towards improved overall survival with Enhertu-Perjeta that will be watched closely, with further patient follow-up.
Enhertu is already approved as a second-line or later therapy for HER2-positive breast cancer based on the results of the DESTINY-Breast03 trial, as well as several other indications, including HR-positive, HER2-low and ultralow breast cancer, and has been growing fast with sales rising to $3.75 billion last year from $2.57 billion in 2023.
AZ and Daiichi Sankyo said they intend to move ahead quickly with submissions for first-line use on the strength of the new data. Only the top-line result is available for now, but they indicated that the improvement in PFS was "highly statistically significant."
DESTINY-Breast09 is also comparing Enhertu monotherapy with THP in another arm of the 1,157-patient study, but the data for that hasn't been unblinded yet. The study is due to be completed in July.
"These new findings suggest that starting Enhertu in combination with pertuzumab at the time of metastatic diagnosis delays disease progression, postponing the time until additional treatment may be needed," commented Ken Takeshita, Daiichi Sankyo's global R&D chief.
Safety data from the new study will be closely watched, as Enhertu has been linked to some potentially serious side effects, including interstitial lung disease (ILD), although, the taxane component of THP can also be hard to tolerate, spurring the search for alternative regimens.
AZ and Daiichi Sankyo said the safety profile of the Enhertu/Perjeta combination was consistent with the known profiles of each therapy alone.
Photo by Rebekah Vos on Unsplash
