The FDA has expanded the indications of 2 assays to identify patients with HER2+ breast cancer for treatment with T-DXd.
The FDA has approved additional indications for the Pathway anti-HER2/neu (4B5) Rabbit Monoclonal Primary Antibody and Ventana HER2 Dual ISH DNA Probe Cocktail tests.1 The tests are now approved to help identify patients with HER2-positive metastatic breast cancer who may be eligible for treatment with fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu).
The regulatory decision occurred in conjunction with the FDA approval of T-DXd plus pertuzumab (Perjeta) for the frontline treatment of adult patients with unresectable or metastatic HER2-positive (immunohistochemistry [IHC] 3+ or in situ hybridization–positive) breast cancer, as determined by an FDA-approved test.2 The approval of T-DXd plus pertuzumab was supported by data from the phase 3 DESTINY-Breast09 trial (NCT04784715), which demonstrated that patients who received the combination (n = 383) achieved a median progression-free survival (PFS) of 40.7 months (95% CI, 36.5-not estimable [NE]) as assessed by blinded independent central review (BICR) per RECIST 1.1 criteria vs 26.9 months (95% CI, 21.8-NE) in those treated with trastuzumab (Herceptin), pertuzumab, and a taxane (docetaxel or paclitaxel; THP; n = 387; HR, 0.56; 95% CI, 0.44-0.71; P < .0001).
"Metastatic breast cancer remains a significant challenge," Laura Apitz, the head of the pathology lab at Roche Diagnostics, stated in a news release.1 "Diagnostic advances like these bring much-needed hope for patients. With this approval, our breast diagnostic portfolio can further guide therapy decisions for clinicians, enabling a more personalized approach."
FDA Grants Approval to Diagnostic Tests to Identify Patients With HER2+ Breast Cancer Eligible for T-DXd
The Pathway anti-HER2/neu (4B5) Rabbit Monoclonal Primary Antibody and Ventana HER2 Dual ISH DNA Probe Cocktail tests have been approved by the FDA to help identify patients with HER2+ metastatic breast cancer who may be eligible for treatment with T-DXd.
The expanded indications for the assays occurred at the same time as the FDA approval of T-DXd plus pertuzumab for the first-line treatment of adult patients with unresectable or metastatic HER2-positive (IHC 3+ or iISH+) breast cancer, as determined by an FDA-approved test.
Findings from DESTINY-Breast09 showed that T-DXd plus pertuzumab produced a significant PFS benefit vs THP for the frontline treatment of patients with HER2+ advanced/metastatic breast cancer (HR, 0.56; 95% CI, 0.44-0.71; P < .0001).
What is the Pathway anti-HER2/neu (4B5) Rabbit Monoclonal Primary Antibody test?
The Pathway anti-HER2/neu (4B5) Rabbit Monoclonal Primary Antibody test is used in combination with the fully automated BenchMark Ultra and BenchMark Ultra Plus staining platforms.1 The test standardizes all IHC processes from baking through staining, reducing the chance for human error. The assay also minimizes inherent variability resulting from individual reagent dilution and other processes found in manual and semi-automated IHC approaches. The HER2 (4B5) clone is able to produce consistently high proficiency assessment scores vs other clones and has shown high concordance with HER2 fluorescence in situ hybridization, which enables laboratories to employ the widely adopted and reliable HER2 IHC primary antibody.
The Pathway anti-HER2/neu (4B5) Rabbit Monoclonal Primary Antibody test was previously indicated by the FDA to identify patients with breast cancer who could be eligible for treatment with trastuzumab, ado-trastuzumab emtansine (Kadcyla), or T-DXd.
What is the Ventana HER2 Dual ISH DNA Probe Cocktail?
The Ventana HER2 Dual ISH DNA Probe Cocktail assay is a fully automated ready-to-use brightfield solution that is used to determine HER2 gene status. The assay aids in identifying patients with breast cancer who are eligible for individualized therapy with HER2-directed agents. It is optimized for use with the Ventana Silver ISH DNP Detection Kit and the Ventana Red ISH DIG Detection Kit on the fully automated BenchMark Ultra and BenchMark Ultra Plus staining platforms.
The Ventana HER2 Dual ISH DNA Probe Cocktail assay is an enhanced version of the prior generation test. The new test employs new oligonucleotide probes and highly sensitive detection kits to offer clear results to pathology labs more quickly.
How was DESTINY-Breast09 designed?
DESTINY-Breast09 was a multicenter, open-label study that enrolled adult patients with HER2-positive advanced or metastatic breast cancer.3 Patients were required to have received at least 1 prior line of endocrine therapy for metastatic breast cancer, have a disease-free interval of more than 6 months from the last chemotherapy or HER2-targeted therapy in the neoadjuvant/adjuvant settings, and no other prior systemic treatment for metastatic breast cancer.
Eligible patients were randomly assigned 1:1:1 to receive T-DXd plus placebo, T-DXd plus pertuzumab, or THP. The primary end point was PFS by BICR. Overall survival was the key secondary end point. Other secondary end points included investigator-assessed PFS, overall response rate (ORR), duration of response (DOR), time to second disease progression, and safety and tolerability.
What were the additional safety and efficacy data from DESTINY-Breast09?
Additional data from DESTINY-Breast09 revealed that the investigator-assessed PFS in the T-DXd plus pertuzumab arm was 40.7 months (95% CI, 36.5-not calculable [NC]) vs 20.7 months (95% CI, 17.3-23.5) in the THP arm (HR, 0.49; 95% CI, 0.39-0.61; P < .00001). The ORRs per BICR were 85.1% (95% CI, 81.2%-88.5%) and 78.6% (95% CI, 74.1%-82.5%), respectively. The median DOR values were 39.2 months (95% CI, 35.1-NC) and 26.4 months (95% CI, 22.3-NC), respectively.
In terms of safety, any-grade treatment-emergent adverse effects (TEAEs) occurred in 99.7% of patients in the T-DXd arm (n = 381) compared with 99.0% of patients in the THP arm (n = 382). Serious TEAEs (27.0% vs 25.1%) as well as TEAEs leading to treatment discontinuation (20.7% vs 28.3%), dose interruptions (68.8% vs 49.0%), and dose reductions (45.9% vs 19.9%) occurred in both arms.
References
Roche receives FDA approval for first diagnostic tests to identify HER2-positive metastatic breast cancer patients eligible for Enhertu. News release. Roche. December 15, 2025. Accessed December 16, 2025. https://www.biospace.com/press-releases/roche-receives-fda-approval-for-first-diagnostic-tests-to-identify-her2-positive-metastatic-breast-cancer-patients-eligible-for-enhertu
FDA approves fam-trastuzumab deruxtecan-nxki with pertuzumab for unresectable or metastatic HER2-positive breast cancer. FDA. December 15, 2025. Accessed December 16, 2025. https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-fam-trastuzumab-deruxtecan-nxki-pertuzumab-unresectable-or-metastatic-her2-positive
Tolaney SM, Jiang Z, Zhang Q, et al. Trastuzumab deruxtecan (T-DXd) + pertuzumab (P) vs taxane + trastuzumab + pertuzumab (THP) for first-line (1L) treatment of patients (pts) with human epidermal growth factor receptor 2–positive (HER2+) advanced/metastatic breast cancer: interim results from DESTINY-Breast09. J Clin Oncol. 2025;43(suppl 17):LBA1008. doi:10.1200/JCO.2025.43.17_suppl.LBA1008
