Breast cancer, new 'tailor-made' therapy for advanced forms arrives

Small steps are being taken in the search for new treatments capable of opening up prospects for curing breast cancer. With the certainty that science is moving forward, to provide specific answers on the basis of the characteristics of the cells that cause the disease, perhaps even exploiting the association between different mechanisms of action to 'hit' the tumour cells from several sides. This could be the strategy guiding the course of treatment of specific advanced forms of breast cancer, also in the light of the expansion of the therapies available for the more serous and advanced forms. The Italian Medicines Agency (AIFA) has approved the reimbursability of capivasertib, a new targeted therapy. The molecule is indicated, in combination with fulvestrant, in patients with locally advanced or metastatic oestrogen receptor positive (ER+), HER2 negative (HER2-) breast cancer. But it is not only this definition that delimits the 'fence' of the drug's possible uses, at least for the time being. The therapy has in fact also been approved in the presence of one or more PIK3CA/AKT1/PTEN alterations, in patients who have developed a relapse or disease progression during or after hormone therapy.

In general terms, each year there are more than 53,000 new breast cancer diagnoses in women in Italy. The HR+ and HER2- subtype is the most frequent and obviously, as the disease progresses, it is becoming increasingly important to find treatments that positively change the trajectory of the disease in advanced or metastatic stages. "In the advanced phase, this type of tumour is treated in the first instance with cyclin-dependent kinase 4 and 6 (CDK4/6i) inhibitors in combination with an endocrine agent," explains Valentina Guarneri, Director of UOC Oncology 2 at the Veneto Oncology Institute and Professor of Medical Oncology at the University of Padua. "The management of patients with tumours progressing to CDK4/6i represents an important clinical challenge today, especially because of endocrine resistance mechanisms.

AIFA's decision is based on the results of the Phase III CAPItello-291 study, published in the New England Journal of Medicine. Capivasertib, in combination with fulvestrant, reduced the risk of disease progression or death by 50 per cent compared to placebo alone in patients with cancer characterised by one or more mutations in the AKT pathway. Median progression-free survival was more than doubled (7.3 months versus 3.1 months). 'A total of 708 patients with HR-positive, HER2-negative breast cancer were enrolled in the study, 70 per cent of whom had already received previous treatment with CDK4/6i,' she continues. The addition of capivasertib to fulvestrant (a hormonal therapy) resulted in a clinically relevant benefit in terms of reduced risk of progression. The combination therefore represents an important therapeutic option for patients who may still benefit from endocrine-based therapy, allowing chemotherapy to be postponed'.

As can be understood, the characteristics of the neoplastic cells are the basis of whether or not the oncologist can use the new drug. Indeed, it is necessary to act specifically on cells that have the mutations that make them 'targets' for this therapy. "PIK3CA, AKT1 and PTEN mutations affect about half of all cases of HR+/HER2- advanced breast cancer," explains Nicola Fusco, Director of the Division of Pathological Anatomy at the IEO and Associate Professor of Pathological Anatomy at the Department of Oncology and Haemato-Oncology of the University of Milan. "These are commonly driver mutations, already detectable at the level of the primary tumour. These alterations represent a known mechanism of endocrine resistance and their presence usually correlates with worse clinical outcomes, which highlights the need for personalised treatments. 'Patients with these alterations may benefit from the capivasertib-fulvestrant combination, and it is therefore crucial that clinicians always test for biomarkers,' reports the expert. Effective and timely collaboration between oncologists and pathologists is now essential to develop personalised treatment strategies'