by Dr. C.H. Weaver M.D. updated 9/2022
Herceptin® (trastuzumab) is currently FDA approved for use as a single agent or in combinations for the treatment of HER-2 over expressing metastatic/advanced breast cancer.
About Herceptin and HER2 + Breast Cancer
A significant portion of patients with breast cancer over-express the human epidermal growth factor-2 (HER-2), which is a protein that is displayed on the outside of a cell. HER-2 is involved in cellular growth and replication, and over expression of HER-2 is implicated in the uncontrolled growth of cancer. The level of HER-2 expression may be determined through laboratory processes. Herceptin® is a monoclonal antibody that has been made through laboratory processes to bind to HER-2, and ultimately inactive or slow the growth and replication pathway that HER-2 is involved in.
Herceptin combination are the standard of care for the treatment of early stage HER2+ breast cancer and the initial treatment of advanced disease.
Herceptin Combinations for Advanced Breast Cancer
The FDA approved Perjeta® (pertuzumab) for the treatment of HER2-positive, metastatic breast cancer in combination with Herceptin® (trastuzumab) and docetaxel chemotherapy in patients who have not received prior anti-HER2 therapy or chemotherapy for metastatic disease. The THP regimen is a preferred initial treatment.
Tukysa for Second Line Treatment
Tukysa (tucatinib) in combination with Herceptin (trastuzumab) and Xeloda (capecitabine) improves outcomes for women with locally advanced unresectable or metastatic HER2-positive breast cancer compared to treatment with Herceptin and Xeloda alone. The US Food and Drug Administration approved Tukysa on April 17, 2020. Importantly The Tukysa regimen is also very effective for treating brain metastases.
Taxotere® Plus Herceptin®
The treatment combination consisting of Taxotere® (docetaxel) and Herceptin® appears effective and well tolerated as initial therapy for patients with HER-2 over expressing metastatic breast cancer.1
Researchers from several U.S. Cancer centers conducted a clinical trial to evaluate the combination of Taxotere® plus Herceptin® in the treatment of metastatic breast cancer. This trial included 26 women with HER-2 over expressing metastatic breast cancer; approximately half of whom had never received prior therapy. Patients were allowed to only have one prior chemotherapy regimen. The overall anti-cancer response rate for these patients was 50%. Patients who strongly over expressed HER-2 had an overall anti-cancer response rate of 64%. In addition, 31% of patients experienced disease stabilization following therapy. The average time to cancer progression was approximately 1 year, and the average duration of survival was nearly 2 years (22 months). Treatment was generally well tolerated.
In patients with human epidermal growth factor receptor (HER2)–positive advanced breast cancer, the combination of Herceptin® (trastuzumab) plus a taxane resulted in delayed time to cancer progression and was associated with fewer side effects than Tykerb® (lapatinib) plus a taxane.
Understanding DNA Damage Response or DDR and Cancer Treatment
What is DNA Damage Response or DDR?
The NCIC Clinical Trials Group enrolled and evaluated 537 patients in 21 countries with HER2 - positive advanced breast cancer that were treated with a taxane plus Tykerb or Herceptin.
The investigators reported that patients taking Tykerb plus a taxane experienced a median progression-free survival of 9.0 months compared to 11.3 months for those taking Herceptin plus a taxane.
Herceptin - Chemotherapy Combinations
Xeloda® + Herceptin® and Taxotere® Delays Cancer Progression in Advanced Breast Cancer
The addition of Xeloda® (capecitabine) to Herceptin® and Taxotere® delays cancer progression among patients with advanced breast cancer by 4.5 months.
The CHAT trial, included 222 patients with advanced, HER2-positive breast cancer. One-hundred-ten participants were treated with Herceptin plus Taxotere, and 112 were treated with Xeloda, Herceptin, and Taxotere.
- Half of the patients treated with Xeloda/Herceptin/Taxotere had cancer progression at 18.2 months, compared with only 13.8 months for those treated with Herceptin/Taxotere.
- Half of the patients treated with Xeloda/Herceptin/Taxotere were alive without cancer progression at nearly 15 months, compared with nearly 13 months for those treated with Herceptin/Taxotere.
- Treatment with the addition of Xeloda was well tolerated.
The researchers concluded that the addition of Xeloda to Herceptin plus Taxotere delays cancer progression and improves progression-free survival in patients with metastatic, HER2-positive breast cancer. Furthermore, the addition of Xeloda was well tolerated, allowing patients to potentially delay more aggressive therapies for their disease.
Adding Afinitor to Herceptin May Provide Breast Cancer Benefit
Afinitor is an oral medication that works by inhibiting a protein known as mTOR. The mTOR protein plays an important role in regulating cancer cell division and blood vessel growth.
To evaluate the combination of Herceptin and Afinitor, researchers combined information from two clinical trials that were conducted concurrently. Information was available for 47 women with HER2-positive metastatic breast cancer that had progressed during treatment with Herceptin. Study participants received Herceptin every three weeks in combination with daily Afinitor.
- Seven patients (15%) had a partial response to treatment (a reduction in detectable cancer).
- An additional nine patients (19%) experienced stable disease for six months or longer.
- Median duration of survival without cancer progression was 4.1 months.
These results suggest that the combination of Afinitor and Herceptin may benefit women with HER2-positive, advanced breast cancer that has worsened in spite of Herceptin treatment.
- Docetaxel Combined with Trastuzumab is an Active Regimen in HER-2 3+ Overexpressing and Fluorescent In Situ Hybridization-Positive Metastatic Breast Cancer: A Multi-Institutional Phase II Trial. Journal of Clinical Oncology. 2004;22:1071-1077.
- Extra JM, Cognetti F, Chan S et al. First-line trastuzumab (Herceptin®plus docetaxel versus docetaxel alone in women with HER2-positive metastatic breast cancer (MBC): results from a randomized phase II trial (M77001). Breast Cancer Res and Treat, 82: Special Issue: 26th Annual San Antonio Breast Cancer Symposium. 2003; Abstract 217.
- Reference: Gelmon K, Boyle F, Kaufman B, et al. Lapatinib or Trastuzumab Plus Taxane Therapy for Human Epidermal Growth Factor Receptor 2–Positive Advanced Breast Cancer: Final Results of NCIC CTG MA.31. J. Clin. Oncol. 2015 Mar. 16 doi:10.1200/JCO.2014.56.9590
- Wardley A, Anton-Torres A, Pivot X, et al. Trastuzumab plus docetaxel with or without capecitabine in patients with HER2-positive advanced/metastatic breast cancer: Primary efficacy results from a randomized phase II study (CHAT). Presented as a late-breaking abstract (LBA6) at the 2006 meeting of the European society of Medical Oncology.
- Reference: Khanh Morrow P, Wulf GM, Ensor J et al. Phase I/II study of trastuzumab in combination with everolimus (RAD001) in patients with HER2-overexpressing metastatic breast cancer who progressed on trastuzumab-based therapy. Journal of Clinical Oncology. Early online publication July 5, 2011.