AstraZeneca and Daiichi Sankyo have added a seventh cancer indication for its antibody-drug conjugate (ADC) Enhertu (trastuzumab deruxtecan) in the US.
The US Food and Drug Administration (FDA) has approved the use of the therapy in unresectable or metastatic hormone receptor (HR)-positive, HER2-low (IHC 1+ or IHC 2+/ISH-) or HER2-ultralow (IHC 0 with membrane staining) breast cancer patients whose disease has progressed after at least one prior line of endocrine therapy.
The label expansion allows for a broader use of Enhertu in breast cancer patients. In May 2022, the US FDA approved its use in patients with unresectable or metastatic HER2-positive breast cancer who have received a prior anti-HER2-based regimen. A few months later, the agency expanded its use in unresectable or metastatic HER2-low (IHC 1+ or IHC 2+/ISH-) breast cancer patients.
Enhertu is a HER2-directed ADC being jointly developed and commercialized by AstraZeneca and Daiichi Sankyo. It has been approved by the US FDA in other solid tumor indications including HER2 mutant non-small cell lung cancer and HER-2 positive advanced gastric cancer. The ADC is a high-grossing drug for AstraZeneca, raking in $1.4 billion over the first nine months last year.
The news comes a few days after the US FDA approved a label expansion for another of AstraZeneca and Daiichi Sankyo’s ADC, Datroway (datopotamab deruxtecan or Dato-DXd). The regulatory agency has approved the therapy as a treatment for HR-positive, HER2-negative (IHC 0, IHC 1+, or IHC 2+/ISH-) breast cancer patients who have received prior endocrine-based therapy and chemotherapy for unresectable or metastatic disease.
Phase III trial data
The US FDA approval was based on the positive Phase III DESTINY-Breast06 trial (NCT04494425) data. The open-label study enrolled 866 patients and compared the safety and efficacy of Enhertu with the investigator’s choice of chemotherapy.
Enhertu showed a 36% reduction in the risk of disease progression or death compared to chemotherapy. The median progression-free survival (PFS) was 13.2 months in the Enhertu group compared to 8.1 months seen in the chemotherapy arm. The objective response rate (ORR) was 62.6% and 34.4% for Enhertu and chemotherapy groups, respectively.
Adverse events of grade 3 or higher occurred in 52.8% of the patients in the Enhertu group and 44.4% of those in the chemotherapy group. Commonly observed grade 3 or higher adverse events included adjudicated interstitial lung disease (ILD) and pneumonitis. Enhertu carries a boxed warning for ILD and embryo-fetal toxicity.
