New drug for metastatic breast cancer: extends and improves life

The goal is to become chronic. If healing from metastatic breast cancer is no longer possible, you can try make the disease chronic and, therefore, live with it, for as long as possible and as well as possible. Making patients gain good quality time is the goal achieved by trastuzumab deruxtecan, a new medicinerecently also approved by the Italian Medicines Agency (Aifa), which reduces the risk of disease progression or death by 50%This drug had received the green light from Aifa in July 2023 for a certain subtype of breast cancer (HER2 positive), also with brain metastases in patients who have already had a first line of treatment – remember Giampaolo Bianchini, associate professor and head of the breast group of the IRCSS San Raffaele Hospital, Vita-Salute San Raffaele University of Milan -. Now the Italian reimbursement is added for another subtype (the so-called HER2 low), for which we only had chemotherapy available with which we obtained unsatisfactory results.

The results of the study

Specifically, AIFA has approved the reimbursement of trastuzumab deruxtecan as monotherapy for the treatment of adult patients (female and male) with HER2 low unresectable or metastatic breast cancerwho have received prior chemotherapy for or have developed metastatic disease relapse of the disease during or within six months of completing adjuvant chemotherapy (i.e. after surgery). The approval for this new indication came in the light of the important results achieved by the DESTINY-Breast04 study, also presented with great prominence during the American oncology congress in 2022. The trial compared 557 patients with an inoperable HER2-low type carcinoma or metastatic chemotherapy with the trastuzumab deruxtecan conjugated antibody, specifically engineered to be directed against the HER2 receptor – explains Bianchini –. And its results have changed the current standard chemo because they have demonstrated that using trastuzumab deruxtecan it is possible to maintain the neoplasm under control for a longer time: doubles the time free from disease progression (the time during which the tumor remains stable, going from 5 to 10 months), it also improves survival (from 17 months to over 23), the risk of death is reduced by 50% and the quality of life improvessince they register fewer side effects.

A precise diagnosis is needed

In 2023, in Italy, an estimated 55,900 new cases of breast cancer were estimated and approximately 37 thousand people are living with metastatic disease, a number that is constantly increasing. One in 8 women will get sick during their lifetime (males can also develop it, although it is a very rare event): thanks to the successes in early diagnosis and new therapies, today 87% of patients live 5 years after diagnosis, but especially against the more aggressive forms and in those in the metastatic stage, innovative strategies are needed.
Today we know that many exist different types of breast cancer and fundamental know which histological and molecular subtype is in front of you to be able to choose, among the many therapies available, the most effective one based on the individual case – points out Michelino De Laurentiis, director of the Department of Senological and Thoraco-Pulmonary Oncology, National Cancer Institute IRCCS Pascale Foundation of Naples –. HER2-low tumors represent all tumors that do not have high expression or amplification of the HER2 receptor: in practice over half of the 55 thousand new cases diagnosed in our country per year, but having a precise diagnosis, today more than ever, is a decisive step.

So many different types of breast cancer

Breast cancer is classified into three main subtypes, fundamental for defining the prognosis and the therapeutic approach. These include the human epidermal growth factor receptor 2 positive (HER2+) tumor subtype, the hormone receptor (HR) positive (estrogen or progesterone positive) and simultaneously HER2 negative (HR+/HER2-) luminal tumor subtype, and the triple-negative subtype (negative for all three receptors).
HER2 expression defined as positive or negative. It is determined via a immunohistochemistry tests, which measures HER2 protein levels in a cancer cell (IHC test results are reported as 0, 1+, 2+, or 3+4), and a fluorescent in situ hybridization (FISH) test, which counts copies of the HER2 gene in tumor cells (the latter is carried out only if a 2+ score is obtained from IHC testing). Up to 55% of all breast cancers express low levels of HER2 and, therefore, can be classified as HER2 low – specifies De Laurentiis –. Until now, these tumors were simply classified as HER2 negative and therefore fell among luminal tumors or triple-negative tumors, depending on the presence or absence of hormone receptors. Today, however, given that HER2 low tumors (HER2 1+ or 2+) can benefit from trastuzumab deruxtecan, it becomes essential to identify them precisely by performing a common immunohistochemistry test. For this reason more than ever the role of the multidisciplinary team in the evaluation of patients is necessary and, in particular, a close collaboration between the oncologist and the pathologist who carries out the diagnostic tests.

Drug-conjugated antibodies

Trastuzumab deruxtecan belongs to the category of drug-conjugated antibodies, which are basically composed of two parts: a monoclonal antibody designed to specifically recognize and bind to a very specific target, present only on cancerous cells and not on healthy ones, which brings with it a powerful chemotherapy. On the one hand, this allows for great therapeutic efficacy, because the chemotherapy transported and “dropped” on the target to be hit it has great destructive power; on the other hand, for, the toxicity to normal cells (and therefore for the patient's organism) very reduced given that the targeted treatment – ​​he says Alessandra Fabi, responsible for Precision Medicine in Senology at the Gemelli IRCCS University Polyclinic Foundation in Rome -. Trastuzumab deruxtecan is the first anti-HER2 therapy approved for patients with HER2 low breast cancer. Self until now chemotherapy was the only option available for patients with advanced or metastatic breast cancer with low HER2 expression, it will now be possible (after having received at least one line of chemo) to proceed with this innovative treatment, which allows us to respond to clinical needs that have so far been unmet.

Step forward

A step forward also seen with satisfaction by patient associations: The news that Aifa has approved the reimbursement of the molecule even in HER2-low cases makes us very happy because it represents a new possibility of treatment and offers a chance to those who didn't have it before – he concludes Rosanna D'Antona, president of Europa Donna Italia – . Innovative therapeutic strategies, together with management within breast units and the joint work of the multidisciplinary team, will not only increase the survival of these women, but also their quality of life. For women with metastatic breast cancer, facilitated access to clinical trials and innovative treatments is crucial, as indicated in our “Manifesto on Metastatic Breast Cancer”.

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