AZ, Daiichi score with FDA nod for Enhertu combo in 1st-line breast cancer

 After AstraZeneca and Daiichi Sankyo made waves in June with eye-opening results for Enhertu in a combination treatment for a particular type of breast cancer, the companies have scored an FDA approval in the indication.

The U.S. regulator has signed off on Enhertu combined with Roche’s Perjeta as a first-line treatment for unresectable or metastatic HER2-positive breast cancer as confirmed by an FDA-approved test.

The FDA originally approved antibody-drug conjugate Enhertu in 2019 as a third-line treatment in the indication, then upgraded the nod to second-line use in 2022.

The agency originally endorsed Perjeta, a targeted monoclonal antibody, in 2012 in combination with Roche’s Herceptin and chemotherapy as a first-line treatment for those with HER2-positive metastatic breast cancer. Since then, the regimen, which is referred to as THP, has been the standard of care in the indication.

The new FDA nod is backed by interim results from the Destiny-Breast09 phase 3 trial, which showed that the Enhertu-Perjeta combo lowered patients' risk of progression or death by 44% compared to THP.

“With a median progression-free survival exceeding three years, versus approximately two years with THP, (Enhertu-Perjeta) should become a new first-line standard of care in this setting,” Sara Tolaney, M.D., of the Dana-Farber Cancer Institute and the principal investigator, said in a statement.

The trial showed that median progression-free survival was 40.7 months with the combo compared to 26.9 months for THP. The PFS benefit of Enhertu-Perjeta was consistent across subgroups.

“With this approval, we are bringing Enhertu to the earliest setting for HER2-positive metastatic breast cancer, where optimizing efficacy has an important impact on long‑term outcomes,” Dave Fredrickson, who heads up AZ’s oncology and hematology business unit, said in a release.

In the trial, the safety profile of the combo was consistent with the known profiles of the individual therapies, with no new safety concerns identified. Use of Enhertu did, however, increase the rate of interstitial lung disease (ILD), a known side effect of ADCs developed by Daiichi Sankyo’s DXd platform.

Adjudicated drug-related ILD or pneumonitis occurred in 12% of patients who got Enhertu and Perjeta versus 1% of those who received THP. Most cases in the Enhertu-Perjeta arm were grade 1 or 2, but they included two deaths (0.5%), while all events in the THP arm were grade 1 or 2.

Doctors have become “quite used to managing” the side effect, Tolaney said in June when the companies presented the results at the American Society of Clinical Oncology conference in Chicago.

In another arm of the trial, AZ and Daiichi are investigating Enhertu as a single agent in the indication, but the comparison between it and THP did not reach statistical significance on the progression-free survival endpoint at an interim analysis.

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. Roche reported 2024 sales of Perjeta at $3.6 billion.

https://www.fiercepharma.com/pharma/astrazeneca-daiichi-sankyo-score-fda-nod-enhertu-combo-breast-cancer