Advanced Breast Cancer, Clinical Practice Changes in the Fight Against Brain Metastases

Over 55 thousand women in Italy live with a advanced breast cancer, approximately 20% have the Her2-positive form and some of these also have brain metastases. For these patients, with inoperable or already resistant neoplasia to other treatments, from European Society of Medical Oncology (ESMO) Congress underway in Barcelona Good news is coming. According to new studies presented at the event and simultaneously published in ‘Nature Medicine’, trastuzumab deruxtecan – a new antibody drug conjugate (ADC) specific for the Her2 receptor – demonstrates a progression-free survival rate of 61.6% at 12 months.

The results of the phase III/IV Destiny-Breast-12 study showed substantial and durable efficacy of the new treatment in 504 patients with Her2-positive metastatic breast cancer, including those with brain metastases. In the cohort with brain metastases (263), the progression-free survival rate at 12 months was 61.6%. The 504 patients enrolled in the study had shown disease progression on previous lines of therapy.

“Trastuzumab deruxtecan belongs to a new class of drugs in oncology – explains Giampaolo Bianchini, associate professor and head of the Breast Group at the IRCCS Ospedale San Raffaele, Vita-Salute San Raffaele University in Milan – It is made up of a monoclonal antibody, which recognizes a therapeutic target on the tumor cell (the Her2 protein), and a very potent chemotherapeutic that is attached to the antibody via a bond (linker) that is broken inside the tumor cell. In short, the antibody acts as a Trojan horse to deliver chemotherapy into the cell in a targeted manner. This approach is also called ‘smart’ chemotherapy. The presence of brain metastases has always been perceived by both doctors and patients as a very serious situation with limited therapeutic options, generally limited to radiotherapy, because many commonly used drugs are unable to reach the brain metastases or have extremely limited efficacy on them”.

“The most important result of the Destiny-Breast12 study – Bianchini underlines – was to demonstrate that, in women with brain metastases from Her2-positive neoplasia already treated with radiotherapy or not treatable with local therapies (neither radiotherapy nor surgery), this drug is able to significantly reduce the size of the brain lesions in more than 2 out of 3 patients (ORR at the central nervous system level 71.7%), some with a complete disappearance of the visible disease. Furthermore, 12 months after the start of treatment, 61.6% of the patients were still benefiting from it”.

“Targeted therapies have changed the history of Her2-positive metastatic breast cancer and today many women have a long life expectancy. However, there remains a strong clinical need for even more effective tools for metastatic disease already treated with standard therapy, particularly in the presence of brain metastases – says Valentina Guarneri, director of Oncology 2 at the Veneto Oncology Institute – IRCCS of Padua and full professor of Medical Oncology at the University of Padua – The Destiny-Breast12 study involved 504 patients with previously treated Her2-positive metastatic disease, with or without brain metastases. About 250 had brain metastases. This is a very important aspect, because patients with brain metastases are often excluded from registration studies or are enrolled in very low numbers. But in Her2-positive disease, a significant percentage of patients, up to 50%, can develop brain metastases. Therefore, it is crucial to have prospective studies designed for people with these characteristics, which are very difficult to manage.”

“In the Destiny-Breast12 study – Guarneri highlights – even patients with brain metastases, who historically have an unfavorable prognosis, achieved a very long overall survival. At 12 months, the latter was greater than 90% in both groups of patients, with and without brain metastases. This is a very important fact, if we consider that these are women who have already followed one or two lines of treatment for the metastatic disease. Systemic therapy with trastuzumab deruxtecan is therefore very effective in controlling brain metastases. Furthermore, the value of research in our country is confirmed. The 7 Italian centers have enrolled a total of 87 patients out of a total of 504 in the study”.

Breast cancer is the second most common cancer and a leading cause of cancer death worldwide. In 2022, more than 2 million breast cancers were diagnosed, resulting in more than 665,000 deaths globally. In Italy, 55,900 new diagnoses of breast cancer were estimated in 2023. While survival rates are high for early diagnosis of breast cancer, only about 30% of patients diagnosed with metastatic disease or progressing to metastatic disease are expected to be alive 5 years after diagnosis.

Trastuzumab deruxtecan is a DXd monoclonal antibody drug conjugate (ADC) specific for the HER2 receptor formulated by Daiichi Sankyo and jointly developed and commercialized by Daiichi Sankyo and AstraZeneca.