AstraZeneca and Daiichi Sankyo write the 'next chapter' in Enhertu's saga with head-to-head win versus Roche's Kadcyla

As AstraZeneca and Daiichi Sankyo seek to rewrite the breast cancer playbook—and dethrone Roche’s MVP Kadcyla—the question is becoming not who should get the partners’ Enhertu, but who shouldn’t.

That’s according to Dave Fredrickson, executive vice president of AstraZeneca’s oncology business unit, who recently sat down with Fierce Pharma to discuss the antibody-drug conjugate’s “game-changing” readouts at this year’s meeting of the San Antonio Breast Cancer Symposium (SABCS).

Chief among those results were updated outcomes from Enhertu’s head-to-head trial against Kadcyla, DESTINY-Breast03, plus findings from a later-line breast cancer confirmatory trial dubbed DESTINY-Breast02.

In its clinical sparring match with Kadcyla in metastatic breast cancer, Enhertu helped HER2-positive patients who'd received one prior therapy live "significantly longer," according to a SABCS press release.

And in the DESTINY-Breast02 confirmatory trial, Enhertu trumped capecitabine-based chemotherapy at helping patients achieve higher response rates and live longer in the third-line, HER2-positive setting after being treated with Kadcyla.

As Fredrickson sees it, DESTINY-Breast02 represents an “important part of the story” for Enhertu as the study confirms the drug's value against conventional chemotherapy-based regimens in late-line disease. But DESTINY-Breast03 is writing the “next chapter” for the drug by moving into the second-line setting, he explained.

In the head-to-head study against Roche’s Kadcyla, Enhertu charted a staggering 36% reduction in death over Kadcyla, which was statistically significant. What's more, Enhertu yielded a 22-month improvement in median progression-free survival, investigators found. Patients on Enhertu lived a median of 28.8 months without disease progression versus 6.8 months for those who received Roche's med. 

The results are significant because Kadcyla was, “until recently, seen as the most advanced technology that was available to treat second-line HER2-high metastatic breast cancer,” Fredrickson explained.

Under the current treatment paradigm, tens of thousands of women worldwide with metastatic HER2-high breast cancer are “ultimately not having acceptable five-year survival rates,” Fredrickson said, raising the need for “new options."

Enhertu previously snared second-line approval based on progression-free survival data versus Kadcyla.

This past summer, meanwhile, the ADC made history with an FDA nod as the first therapy targeted to treat unresectable or metastatic breast cancer expressing low levels of HER2, unlocking a new category previously consigned to the HER2-negative group. That approval was based off the landmark trial DESTINY-Breast04.

“I will say that so far today when I talk to investigators that right now, there’s more of a mindset that we’re trying to figure out who shouldn’t get Enhertu as opposed to who should,” Fredrickson added.

Aside from Enhertu’s SABCS performance, AstraZeneca and Daiichi also rolled out data on their triumvirate of clinical candidates datopotamab deruxtecan (Dato-DXd), camizestrant and capivasertib.

“Breast cancer is not a single disease,” Fredrickson said, highlighting the malignancy’s multiple stages and subtypes.

“It’s very heterogenous,” he explained, noting that while “[w]e’ve made a lot of progress as a field,” there remains “tremendous unmet need.”

The goal then, is to tackle the breast cancer spectrum on as many fronts as possible, Fredrickson added.

“I think that at San Antonio, you see four breast cancer medicines within our portfolio aiming to do just that.”