Enhertu’s market conquest is continuing apace. Already tracking at $5 billion in annual sales, the star antibody-drug conjugate from Daiichi Sankyo and AstraZeneca has secured FDA approval to treat early breast cancer, further encroaching on Roche’s Kadcyla territory.
The FDA has simultaneously greenlighted Enhertu for both the neoadjuvant and adjuvant treatment of patients with HER2-positive early breast cancer, the two companies said Friday. The adjuvant nod came nearly two months ahead of schedule, as the FDA had originally targeted a decision by July 7.
While early, the adjuvant label comes with a catch: It precludes patients who’ve received Enhertu before surgery from continuing on the HER2-directed ADC in the post-operative setting.
Specifically, in the adjuvant setting, Enhertu is now approved for patients with HER2-positive breast cancer who have residual invasive disease following treatment with trastuzumab (Herceptin)—with or without Roche’s Perjeta—and taxane-based treatment. When announcing an FDA priority review in March, Daiichi and AZ described the indication as for “after neoadjuvant HER2 targeted treatment,” which, if approved verbatim, would cover prior use of Enhertu. But apparently a broad label did not pan out.
As for the neoadjuvant setting, Enhertu is cleared on top of the THP regimen (a taxane, Herceptin and Perjeta) for treating adults with HER2-positive stage 2 or stage 3 breast cancer.
Despite the label restriction, some doctors may still use Enhertu in the adjuvant setting following neoadjuvant Enhertu.
Enhertu’s adjuvant early breast cancer indication is backed by data from the Destiny-Breast05 trial showing the drug reduced the risk of invasive disease recurrence or death by 53% compared with Kadcyla.
In the neoadjuvant setting, the Destiny-Breast11 study linked Enhertu, followed by THP, to a pathologic complete response (pCR) rate of 67.3%, significantly higher than the 56.3% for dose-dense doxorubicin and cyclophosphamide followed by THP. A pCR means no residual disease is found in resected tissues.
In interviews with Fierce at the European Society for Medical Oncology annual meeting in October, executives from Daiichi and AZ suggested that because neoadjuvant treatment only involves four cycles of Enhertu, doctors would not hesitate to retreat patients who have residual disease.
“If you’ve only had four cycles of Enhertu and you’ve had a really good response, I don’t think that that says that you’re going to necessarily be resistant to Enhertu for a re-challenge in that setting,” AZ’s oncology R&D chief Susan Galbraith, Ph.D., said at the time.
In a separate interview in January on the sidelines of the J.P. Morgan Healthcare Conference, Daiichi’s head of global oncology business, Ken Keller, acknowledged that doctors are split on whether reusing Enhertu is appropriate, but he suggested that “the majority” agree with the proposed practice because Enhertu is so far the most potent HER2 agent.
But with the adjuvant label excluding prior Enhertu use and the fact that the Destiny-Breast05 study did not enroll patients who had received the ADC as a neoadjuvant treatment, reimbursement for continued use may be a challenge.
Either way, Enhertu’s latest expansion is expected to do a number on Kadcyla, which has been counting heavily on its adjuvant use for any residual growth in the U.S. after losing out to Enhertu in the metastatic setting.
Since its original FDA approval for previously treated metastatic breast cancer in late 2019, Enhertu has transformed the standard of care in HER2-positive breast cancer. It was only in December that the FDA signed off on Enhertu combined with Perjeta as a first-line treatment.
Sales of Enhertu have been on the rise as it has moved up in the treatment sequence and established HER2-low as a new therapeutic area. Combined sales recorded by AZ and Daiichi jumped 31% in the first quarter of 2026, reaching $1.4 billion. For its 2026 fiscal year, which ends in March 2027, Daiichi has projected Enhertu global sales of 861.3 billion Japanese yen ($5.4 billion).
Enhertu is a key pillar in Daiichi’s freshly unveiled five-year plan to have sales above 3 trillion yen by fiscal 2030. The company also aims to be a global top-5 oncology player by 2035, by which time Enhertu will have lost its patient protection.