Enhertu demonstrated a statistically significant and clinically meaningful improvement in PFS against standard-of-care chemotherapy in the primary trial population
AstraZeneca and Daiichi Sankyo’s Enhertu shows positive results in DESTINY-Breast06 Phase 3 trial. (Credit: AstraZeneca)
AstraZeneca and Daiichi Sankyo’s Enhertu (trastuzumab deruxtecan) has improved the progression-free survival (PFS) in DESTINY-Breast06 Phase 3 trial of patients with HR-positive, HER2-low (IHC 1+ or 2+/ISH-) metastatic breast cancer following one or more lines of endocrine therapy.
Discovered by Daiichi Sankyo, Enhertu is a HER2-directed DXd antibody drug conjugate (ADC). It is being jointly developed and commercialised by AstraZeneca and Daiichi Sankyo.
The ADC is already approved for certain breast cancer patients, non-small cell lung cancer, gastric or gastroesophageal junction adenocarcinoma, and solid tumours in several countries.
DESTINY-Breast06 evaluated Enhertu versus the investigator’s choice of chemotherapy in 866 patients.
The primary endpoint was defined as the PFS in the HR-positive, HER2-low patient population as measured by blinded independent central review (BICR).
Key secondary endpoints consist of overall survival (OS) in patients with HER2-low expression and PFS by BICR and OS in the overall trial population.
According to the results, the HER2-directed ADC demonstrated a statistically significant and clinically meaningful improvement in PFS against standard-of-care chemotherapy in the primary trial population.
The same results were also observed in the overall trial population of patients with HER2-low and HER2-ultralow metastatic breast cancer.
Additionally, a prespecified subgroup analysis showed that the clinically meaningful improvement was similar between patients with HER2-low and HER2-ultralow expression.
The OS data were not fully developed during the analysis, but Enhertu displayed an initial inclination towards improving OS compared to standard-of-care chemotherapy in HER2-low patients and across the entire trial cohort.
AstraZeneca said that the trial will proceed as scheduled to further evaluate OS and other secondary endpoints.
AstraZeneca oncology R&D executive vice president Susan Galbraith said: “DESTINY-Breast06 shows that Enhertu could become a new standard of care for patients with HER2-low and HER2-ultralow metastatic breast cancer following one or more lines of endocrine therapy.”
In a similar development, AstraZeneca’s Truqap (capivasertib) in combination with Faslodex (fulvestrant) has been recommended for approval in the European Union to treat estrogen receptor (ER)-positive, HER2‑negative locally advanced or metastatic breast cancer patients.
The Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion for the combination based on the results from the CAPItello-291 Phase 3 trial.