AstraZeneca and Daiichi Sankyo are aiming to establish their star antibody-drug conjugate (ADC) Enhertu as a first-line treatment in HER2-positive breast cancer after recording “highly statistically significant” efficacy in a key trial.
The two companies are preparing applications for Enhertu in first-line breast cancer with regulators after the phase 3 Destiny-Breast09 trial met its main goal, the two companies said Monday.
In the study, a combination of Enhertu and Roche’s Perjeta topped the standard THP regimen—which includes Perjeta, Herceptin and chemotherapy—in delaying tumor progression or death in patients with newly diagnosed HER2-positive metastatic breast cancer.
The improvement in progression-free survival was “highly statistically significant and clinically meaningful,” according to AZ and Daiichi, and it was observed across all pre-specified patient subgroups.
Destiny-Breast09 is “the first trial in more than a decade to demonstrate superior efficacy across a broad HER2 positive metastatic breast cancer patient population compared to the current first-line standard of care,” Susan Galbraith, Ph.D., EVP of oncology hematology R&D at AstraZeneca, said in a statement Sunday.
The trial remains ongoing after the interim analysis. Data on whether the Enhertu-Perjeta combo can extend patients’ lives were not mature, but the results have shown an early positive trend favoring the new regimen, according to AZ and Daiichi.
A second arm of the trial testing Enhertu alone versus THP has yet to read out and will proceed to the final progression-free survival analysis.
Data from the current analysis of Enhertu and Perjeta will be shared at an upcoming medical conference.
To benchmark expectations, the THP regimen won its FDA approval after showing a median progression-free survival time of 18.5 months in first-line HER2-positive breast cancer.
Results published last year from the phase 1/2 Destiny-Breast07 trial in the first-line setting linked the Enhertu-Perjeta combo to an 84% confirmed tumor response rate and an 89.4% 12-month progression-free survival rate based on a data cutoff in December 2023.
While efficacy is a key measurement, industry watchers are also keen to understand Enhertu’s safety profile in first-line treatment, especially on the potentially dangerous side effect of interstitial lung disease (ILD). In Destiny-Breast07, ILD events deemed related to Enhertu happened in 14% of patients who took the ADC and Perjeta. None of the cases were grade 4 or led to death.
Enhertu has shown potential to be one of the most successful medicines in oncology. After pioneering the HER2-low category in breast cancer treatment, the ADC won an FDA approval in January as a second-line treatment for breast cancer with HER2-low or HER2-ultralow expressions.
In 2024, combined sales of Enhertu by AZ and Daiichi reached $3.75 billion, versus $2.57 billion the prior year.