FDA Approves PATHWAY anti-HER2/neu Rabbit Monoclonal Primary Antibody Companion Diagnostic for HER2-Low Breast Cancer


The PATHWAY anti-HER2/neu (4B5) Rabbit Monoclonal Primary Antibody was approved by the FDA as a companion diagnostic to help identify patients with HER2-low metastatic breast cancer who may be eligible to receive fam-trastuzumab deruxtecan-nxki.

Companion diagnostic PATHWAY anti-HER2/neu (4B5) Rabbit Monoclonal Primary Antibody has been approved by the FDA to identify low HER2 expression in patients with metastatic breast cancer who may be able to receive fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu), according to a press release from Roche.1

This test will allow pathologists to identify low expressors of HER2 using a scoring algorithm. The lower cut off should help to better identify patients who may benefit from T-DXd. The diagnostic was used in the phase 3 DESTINY-Breast04 trial (NCT03734029) to help identify HER2 expression.2

“Previously, [patients with] metastatic breast cancer with a lower level of HER2 expression were considered to be part of the HER2-negative population and had no HER2-targeted treatment options. Now, they may be eligible for a HER2-targeted therapy, significantly increasing the number of patients who could have improved outcomes,” Thomas Schinecker, chief executive officer at Roche Diagnostics, said in the press release.

This companion diagnostic is used in conjunction with the BenchMark immunohistochemistry (IHC)/in situ hybridization slide staining instrument, thus standardizing all IHC processes and helping to reduce the possibility of human error. This diagnostic had high proficiency assessment scores compared with other similar clones. It also showed high concordance with HER2 fluorescence in situ hybridization (FISH) testing, and allows for the use of the most widely adopted and reliable HER2-IHC primary antibody.

In August 2022, T-DXd was approved by the FDA for patients with HER2-low breast cancer based on results from the DESTINY-Breast04 trial.3 Patients in the trial were either hormone receptor positive (n = 494) or hormone receptor negative (n = 63).

In the overall population, the median progression-free survival (PFS) was 9.9 months (95% CI, 9.0-11.3) vs 5.1 months (95% CI, 4.2-6.8) in the T-DXd and chemotherapy arms, respectively, (HR, 0.50; 95% CI, 0.40-0.63; P <.0001). In the hormone receptor–positive cohort, the median PFS was 10.1 months (95% CI, 9.5-11.5) in the T-DXd arm vs 5.4 months (95% CI, 4.4-7.1) in the chemotherapy arm (HR, 0.51; 95% CI, 0.40-0.64; P <.0001). In patients with hormone receptor–negative disease, the median PFS was 8.5 months (95% CI, 4.3-11.7) in the T-DXd arm and 2.9 months (95% CI, 1.4-5.1) in the chemotherapy arm (HR, 0.46; 95% CI, 0.24-0.89). Those who had received prior CDK4/6 therapy and were hormone receptor positive had a median PFS of 10.0 months (95% CI, 8.3-11.4) in the T-DXd arm vs 5.4 months (95% CI, 4.0-7.8) in the chemotherapy arm (HR, 0.55; 95% CI, 0.42-0.73).

The median overall survival (OS) for patients in the overall cohort was 23.4 months (95% CI, 20.0-24.8) in the T-DXd group and 16.8 months (95% CI, 14.5-20.0) in the chemotherapy group (HR, 0.64; 95% CI, 0.49-0.84; P = .001). Those who were hormone receptor positive had a median OS of 23.9 months (95% CI, 20.8-24.8) in the T-DXd arm and 17.5 months (95% CI, 15.2-22.4) in the chemotherapy arm (HR, 0.64; 95% CI, 0.48-0.86; P = .0028). The median OS for those who were hormone receptor negative was 18.2 months (95% CI, 13.6-not estimable) in the T-DXd arm and 8.3 months (95% CI, 5.6-20.6) in the chemotherapy arm (HR, 0.48; 95% CI, 0.24-0.95).

Treatment-related adverse effects that occurred between the T-DXd and placebo arms included nausea (73.0% vs 23.8%), fatigue (47.7% vs 42.4%), alopecia (37.7% vs 32.6%), vomiting (34.0% vs 9.9%), neutropenia (33.2% vs 51.2%), and anemia (33.2% vs 22.7%).


  1. Roche receives FDA approval for first companion diagnostic to identify patients with HER2 low metastatic breast cancer eligible for ENHERTU. News Release. Roche. October 4, 2022. Accessed October 5, 2022. https://bit.ly/3e6pps1
  2. Modi S, Jacot W, Yamashita T, et al. Trastuzumab deruxtecan in previously treated HER2-low advanced breast cancer. N Engl J Med. 2022;387(1):9-20. doi:10.1056/NEJMoa2203690
  3. FDA approves fam-trastuzumab deruxtecan-nxki for HER2-low breast cancer. News Release. FDA. August 5, 2022. Accessed October 5, 2022. https://bit.ly/3M7iz1Q
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