THE FASTER WE MOVE

Up to 30% of patients with metastatic breast cancer develop brain disease

As we mentioned in this article, we have commenced two clinical trials for the treatment of patients with breast cancer who have developed metastases in the central nervous system, including the brain and meninges. The objective of both trials is to find an alternative to standard local treatment that allows an increase of progression-free survival of patients with this disease.


Within each type of cancer, we can find different tumor subtypes depending on the expression of certain proteins. In the case of breast cancer, the expression of different hormonal receptors (both estrogen (ER) and progesterone (PgR)), as well as the growth factor receptor HER2, serve to predict the risk of brain metastases. It is currently known that there is an increased risk of cancer spreading to the brain when hormone receptors are negative, or when HER2 expression is positive - this being the most important subtype in terms of the risk of developing this type of metastasis.



In the DEBBRAH clinical trial the efficacy of a drug called trastuzumab deruxtecan (DS-8201) will be tested in patients with advanced HER2-positive breast cancer with metastases in the brain and/or meninges (leptomeningeal carcinomatosis) which have progressed after receiving local treatment. This study will be carried out under the scientific direction of Dr. Sofía Braga, Medical Oncologist at the Hospital Fernando Fonseca in Lisbon (Portugal).




“Trastuzumab deruxtecan is an antibody directed against HER2, the protein responsible for the spread of cancer cells in this subtype of breast cancer. Previous studies have already been carried out with this drug that show good clinical results, even in patients with metastatic breast cancer who have been pretreated with other therapies”, explains Dr. Elisenda Llabrés, medical oncologist and principal investigator at the Hospital Insular de Gran Canaria (Spain).


If the results from the DEBBRAH clinical trial are positive, the drug could be used as an effective treatment option in all patients with metastatic breast cancer, regardless of the presence of brain metastases.





On the other hand, the PHENOMENAL clinical trial will evaluate the efficacy of liposomal irinotecan (nal-IRI) in patients with HER2 negative breast cancer – that is cases that do not express the HER2 protein. Irinotecan works by preventing DNA from being able to replicate when a new cell is to form, which contributes to the paralysis of cell division and, therefore, tumor growth and development. In the case of nal-IRI, irinotecan is surrounded by a capsule of nanoparticles that protect it, which allows more of the active ingredient to reach the place where it has to act, without being degraded along the way or eliminated by the own body.

Similar molecules have shown activity in patients with nervous system involvement in previous clinical trials, which reinforces the hypothesis that nal-IRI may be beneficial in breast cancer patients with brain metastases.

“Given that breast cancer with brain metastases currently has no cure, the current therapeutic objective is to find a treatment capable of slowing the progression of the cancer, making the disease chronic and alleviating its symptoms to maintain a good quality of life for patients ", explains Dr. Kepa Amillano Párraga, medical oncologist at the Hospital Sant Joan de Reus (Spain).




The objective of PHENOMENAL, led by Dr. Javier Cortés, medical oncologist of the International Breast Cancer Center, is to generate the necessary evidence to provide oncologists with new and effective therapeutic options for the treatment of these patients.






Although the survival of patients with breast cancer continues to improve thanks to advances in diagnosis and treatment, the prognosis when brain metastases occur is still very poor, with a survival rate of less than 50% in the first year[1]. Since breast cancer with brain metastases currently has no cure, the current therapeutic objective is to find a treatment capable of slowing the progression of cancer, making the disease chronic and alleviating its symptoms to maintain a good quality of life for patients.







NEWS COVERAGE


DEBBRAH

PHENOMENAL




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[1] José Pablo Leone, Adrian V Lee, Adam M Brufsky. Prognostic factors and survival of patients with brain metastasis from breast cancer who underwent craniotomy. 2015 Jul;4(7):989-94. doi: 10.1002/cam4.439. Epub 2015 Mar 9.

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