On May 15, 2026, the U.S. Food and Drug Administration quietly rewrote the playbook for HER2‑positive early breast cancer, signing off on two new uses for Enhertu (fam‑trastuzumab deruxtecan‑nxki) in adults. The approvals cover an Enhertu‑then‑THP neoadjuvant pathway for stage II and III disease, plus single‑agent Enhertu as adjuvant therapy for patients who still have residual invasive disease after surgery. Clinicians say this could nudge many high‑risk HER2‑positive patients toward a more targeted strategy that often skips anthracycline chemotherapy.
Neoadjuvant trial delivered bigger pathologic responses
In the neoadjuvant DESTINY‑Breast11 trial, patients who received Enhertu followed by paclitaxel, trastuzumab and pertuzumab (THP) hit a centrally assessed pathologic complete response (pCR) rate of 67.3%. Those on the comparison pathway, dose‑dense doxorubicin and cyclophosphamide followed by THP, reached 56.3%. That 11.2‑point edge in pCR was statistically significant.
The study enrolled roughly 900 high‑risk, locally advanced patients and showed benefit across hormone‑receptor subgroups. Investigators also reported lower rates of some severe toxicities in the Enhertu arm, a detail that has not gone unnoticed by oncologists who are weary of classic chemo side effects. The full trial report appears in Annals of Oncology.
Adjuvant data pointed to fewer recurrences
The adjuvant DESTINY‑Breast05 trial enrolled 1,635 patients who still had residual invasive disease after neoadjuvant therapy. At three years, invasive disease‑free survival (IDFS) was 92.4% for those treated with Enhertu versus 83.7% for patients who received trastuzumab emtansine (T‑DM1). That translated to a hazard ratio of 0.47 and more than a 50% relative reduction in recurrence or death.
The result met the trial’s primary endpoint and effectively underpinned the FDA’s adjuvant approval. The full dataset is published in The New England Journal of Medicine.
Safety: lung and heart risks, but less classic chemo punch
In the neoadjuvant setting, adjudicated drug‑related interstitial lung disease (ILD) or pneumonitis showed up in roughly 4–5% of patients across arms, figures investigators described as low and generally manageable with careful monitoring. Enhertu‑based therapy also came with fewer grade ≥3 events, fewer serious adverse events and a lower rate of left‑ventricular dysfunction than the anthracycline‑containing regimen, at roughly 1.3% versus about 6% in the comparator group.
Those safety signals helped shape the overall risk‑benefit picture for many doctors who are weighing potency against long‑term toxicity. Detailed safety breakdowns are summarized in the sponsor’s approval release from Daiichi Sankyo.
Practical takeaways for patients and doctors
The FDA label includes a boxed warning for ILD/pneumonitis along with specific monitoring guidance. For neoadjuvant treatment, the agency lists a recommended dose of 5.4 mg/kg of Enhertu every three weeks for four cycles, followed by four cycles of THP. In the adjuvant setting, Enhertu is dosed at 5.4 mg/kg every three weeks for up to 14 cycles.
The approval also covers companion diagnostic tests to pinpoint HER2‑positive patients who are eligible for Enhertu, and it urges clinicians to report serious adverse events through MedWatch. Prescribing details and testing recommendations are outlined in the FDA’s approval announcement and full prescribing information from the FDA.
What oncologists are saying
For investigators like Dr. Shanu Modi of Memorial Sloan Kettering Cancer Center, the decision feels less like a subtle tweak and more like a meaningful upgrade. “I don’t see a downside in using a more effective therapy that’s less toxic for our patients,” she told CURE Today.
As cancer centers roll out the new indications, oncologists will still need to factor in each patient’s lung‑toxicity risk, cardiac history and access issues when walking through treatment options, even with a high‑powered new tool like Enhertu in the kit.
