Based on DESTINY-Breast09 phase 3 trial results that showed Daiichi Sankyo and AstraZeneca’s ENHERTU in combination with pertuzumab reduced the risk of disease progression by 44% versus THP with a median progression-free survival of more than three years
ENHERTU in combination with pertuzumab has been approved in the U.S. as a first-line treatment for adult patients with unresectable or metastatic HER2 positive (immunohistochemistry [IHC] 3+ or in-situ hybridization (ISH)+) breast cancer, as determined by a U.S Food and Drug Administration (FDA)-approved test.
ENHERTU is a specifically engineered HER2 directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo (TSE: 4568) and being jointly developed and commercialized by Daiichi Sankyo and AstraZeneca.
The approval was based on results from the DESTINY-Breast09 phase 3 trial, presented during a special late-breaking oral session at the 2025 American Society of Clinical Oncology (#ASCO25) Annual Meeting and subsequently published in The New England Journal of Medicine. The FDA completed the review under its Real Time Oncology Review (RTOR) program, an initiative of the FDA, following Priority Review and Breakthrough Therapy Designation of ENHERTU in combination with pertuzumab in the U.S. in this setting. The expanded approval for ENHERTU in the U.S. enables its use earlier as part of a combination regimen in the first-line setting of patients with HER2 positive metastatic breast cancer.
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In DESTINY-Breast09, ENHERTU in combination with pertuzumab reduced the risk of disease progression or death by 44% versus taxane, trastuzumab and pertuzumab (THP) (hazard ratio [HR]: 0.56; 95% confidence interval [CI]: 0.44-0.71; p<0.0001) in patients with HER2 positive metastatic breast cancer who had not received prior chemotherapy or HER2 targeted therapy or had received neoadjuvant or adjuvant HER2 targeted therapy more than six months before the diagnosis of advanced or metastatic disease. Median progression-free survival (PFS) was 40.7 months (95% CI: 36.5-not estimable [NE]) with ENHERTU in combination with pertuzumab compared to 26.9 months (95% CI: 21.8-NE) for THP as assessed by blinded independent central review (BICR).
Confirmed objective response rate (ORR) was 87% (95% CI: 83-90) with ENHERTU in combination with pertuzumab compared to 81% (95% CI: 77-85) with THP. The ENHERTU in combination with pertuzumab arm showed that 15% of patients achieved a complete response (CR) and 72% achieved a partial response (PR) while in the THP arm, 8% of patients achieved a CR and 73% achieved a PR.
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“Trastuzumab deruxtecan plus pertuzumab is the only first-line treatment approved in more than a decade to demonstrate a statistically significant improvement in progression-free survival over the current standard regimen for patients with HER2 positive metastatic breast cancer,” said Sara Tolaney, MD, MPH, Chief of the Division of Breast Oncology, Dana-Farber Cancer Institute and Principal Investigator for the DESTINY-Breast09 trial. “With a median progression-free survival exceeding three years versus approximately two years with THP, trastuzumab deruxtecan combined with pertuzumab should become a new first-line standard of care in this setting.”
ENHERTU is approved with Boxed WARNINGS for interstitial lung disease (ILD)/pneumonitis and Embryo-Fetal toxicity. The safety of ENHERTU in combination with pertuzumab was evaluated in 381 patients with unresectable or metastatic HER2 positive breast cancer in DESTINY-Breast09. The most common (≥20%) adverse reactions, including laboratory abnormalities, were decreased white blood cell count, decreased hemoglobin, decreased neutrophil count, nausea, increased alanine aminotransferase, diarrhea, increased aspartate aminotransferase, decreased lymphocyte count, decreased platelet count, increased blood alkaline phosphatase, decreased blood potassium, fatigue, alopecia, vomiting, upper respiratory tract infection, constipation, decreased appetite, decreased weight, COVID-19, musculoskeletal pain, increased blood bilirubin and abdominal pain. Serious adverse reactions occurred in 27% of patients receiving ENHERTU in combination with pertuzumab. Serious adverse reactions in >1% of patients who received ENHERTU in combination with pertuzumab were diarrhea, pneumonia, febrile neutropenia, hypokalemia, vomiting, ILD, pulmonary embolism, and sepsis. Fatalities due to adverse reactions occurred in 3.4% of patients.
“Since its initial approval six years ago, ENHERTU has transformed the treatment of HER2 positive metastatic breast cancer,” said Ken Keller, Global Head of Oncology Business, and President and CEO, Daiichi Sankyo, Inc. “With this approval in the first-line metastatic setting, ENHERTU once again offers significant improvements in progression-free survival and has practice-changing potential when used in combination with pertuzumab.”
“With this approval, we are bringing ENHERTU to the earliest setting for HER2 positive metastatic breast cancer, where optimizing efficacy has an important impact on long-term outcomes,” said Dave Fredrickson, Executive Vice President, Oncology Hematology Business Unit, AstraZeneca. “The treatment approach with ENHERTU plus pertuzumab in DESTINY-Breast09 sets a new benchmark of more than three years without disease progression or death for patients in this setting.”
This application in the U.S. also was reviewed under Project Orbis, which provides a framework for concurrent submission and review of oncology medicines among participating international partners. As part of Project Orbis, reviews are ongoing in Switzerland and with other regulatory authorities. A separate regulatory application also is under review in Japan based on DESTINY-Breast09.
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Source- businesswire
