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Does Kadcyla cross the blood brain barrier?

Medically reviewed by Melisa Puckey, BPharm. Last updated on Oct 8, 2021.

Can Kadcyla be used to treat brain metastasis?

Official answer

by Drugs.com
  • It was believed that Kadcyla was too large to cross the blood brain barrier (BBB).
  • For medicines to treat brain cancer they need to be able to get through the BBB and into the tumor.
  • Recent studies suggest that when there is a brain tumor the BBB may become more leaky allowing Kadcyla (ado-trastuzumab emtansine) to cross into the brain to help treat the brain tumor.

Breast cancer patients have a risk of 5% to 15% of developing brain metastases and if the breast cancer is HER2 positive breast cancer the risk of brain metastases can be higher, up to 25%.

What is the blood brain barrier?

  • The BBB is a barrier that only lets selective substances cross into the brain.
  • It protects the brain from harm by preventing toxins, pathogens, and certain drugs from passing into the brain.
  • For medicines to treat brain cancer they need to be able to get through the BBB and into the tumor.
  • Some medicines are small enough to pass through into the BBB but others are too large.
  • More recently emerging evidence suggests that when a tumor is present in the brain, it may disrupt the BBB so larger medicines may be able to pass through the BBB and reach the tumor.


Kadcyla and the BBB

In the EMILIA clinical study:

  • They looked at HER2 positive breast cancer patients who had CNS metastases without symptoms, who were treated at baseline with Kadcyla.
  • It was noted that overall survival of Kadcyla treated patients was significantly improved when compared with the capecitabine–lapatinib treated patients.
  • Kadcyla effectiveness was thought to be due to the brain tumor making the BBB leaky which let more Kadcyla into the tumor.
  • More studies and clinical trials are needed to determine how effective Kadcyla is against breast cancer that has metastasized to the brain.

Bottom line:

  • Kadcyla was originally thought to be too big to cross the BBB however the EMILIA clinical trial showed an increased overall survival in HER2 positive breast cancer patients who had CNS metastases without symptoms.
  • This suggests that when a brain tumor is present the BBB becomes leaky and Kadcyla was able to pass through the BBB and into the brain tumor.
  • More studies are needed for Kadcyla to check its effectiveness for the treatment of HER2-positive breast cancer that has metastasized to the brain.
References
  • Trastuzumab emtansine (T-DM1) versus lapatinib plus capecitabine in patients with HER2-positive metastatic breast cancer and central nervous system metastases: a retrospective, exploratory analysis in EMILIA: [Accessed 8/10/2021] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4679405/
  • Activity of Trastuzumab-emtansine (TDM1) in HER2-Positive breast cancer brain metastases: A case series. [Accessed 8/10/2021] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4840897/
  • Targeted Brain Tumor Treatment-Current Perspectives: [Accessed 8/10/2021] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3155235/
  • Efficacy of Ado-trastuzumab Emtansine in the Brain Microenvironment [Accessed 8/10/2021] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4862418/
  • Efficacy and safety of trastuzumab emtansine (T-DM1) in patients with HER2-positive breast cancer with brain metastases [Accessed 8/10/2021] https://pubmed.ncbi.nlm.nih.gov/27167986/
  • Targeting the Sanctuary Site: Options when Breast Cancer Metastasizes to the Brain [Accessed 8/10/2021] https://www.cancernetwork.com/view/targeting-sanctuary-site-options-when-breast-cancer-metastasizes-brain

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