AstraZeneca, Daiichi Continue Earlier-Line Breast Cancer Push with Phase III Enhertu Win

 AstraZeneca and Daiichi Sankyo on Monday released topline findings from the Phase III DESTINY-Breast06 study, showing that their antibody-drug conjugate Enhertu (trastuzumab-deruxtecan) yielded significant survival benefits in certain patients with metastatic breast cancer.

With more than 860 patients enrolled, DESTINY-Breast06 pit Enhertu against an investigator’s choice of chemotherapy, including capecitabine, paclitaxel or nab-paclitaxel. Only patients who were HR positive and with low or ultralow expression levels of the HER2 protein were eligible for enrollment. All study participants had also undergone at least one prior line of endocrine therapy.

Topline results showed that Enhertu treatment led to a “statistically significant and clinically meaningful improvement” in progression-free survival (PFS). This effect remained consistent when focusing specifically on patients with low or ultralow HER2 expression.

However, overall survival (OS) data were not yet mature at the time of the interim analysis. Still, DESTINY-Breast06 detected “an early trend towards an OS improvement versus standard of care chemotherapy” in the overall study population and particularly in the subgroup of patients with low HER2 expression, according to the companies.

DESTINY-Breast06 will continue as planned to evaluate OS and other secondary endpoints.

Susan Galbraith, executive vice president of oncology R&D at AstraZeneca, in a statement said that Monday’s readout reinforces that Enhertu “could become a new standard of care” for HER2 low and HER2 ultralow metastatic breast cancer, following at least one line of endocrine treatment.

“These data underscore the potential for treatment with Enhertu across the spectrum of HR-positive breast cancer, further redefining the treatment of metastatic breast cancer,” Galbraith added.

AstraZeneca and Daiichi Sankyo did not reveal specific data in Monday’s announcement but promised to do so at an upcoming medical congress. The partners will also share their findings to global regulatory authorities, with an eye toward label expansion.

Designed using Daiichi Sankyo’s DXd antibody-drug conjugate (ADC) platform, Enhertu targets the HER2 protein, which is involved in the hyperactive growth and division of cancer cells. It carries a number of topoisomerase I inhibitor payloads, which triggers cell death. The ADC first won the FDA’s approval in December 2019 for hard-to-treat HER2-positive breast cancer.

Earlier this month, Enhertu bagged the FDA’s first tumor-agnostic ADC approval, opening up its use in patients with HER2-positive solid tumors who had undergone prior systemic treatment and who have no available alternative treatment options.

https://www.biospace.com/article/astrazeneca-daiichi-sankyo-continue-earlier-line-breast-cancer-push-with-phase-iii-enhertu-win/