Breast cancer is the most frequent cancer in the adult population and each year more than 2.3 million new cases are detected in the world, according to the World Health Organization (WHO), which indicates that in 95% of countries breast cancer is the first or second leading cause of cancer death in women. About 70% of breast cancers are of the HR+ HER2 type.
Metastatic HR+ HER2- tumors are treated with CDK4/6 inhibitory drugs in combination with endocrine therapy. Treatment options include intramuscular fulvestrant, which is used alone or in combination with other drugs. Now, a phase III clinical trial has shown that the combination of fulvestrant with capivasertib – a new oral drug developed by Astrazeneca – significantly improves progression-free survival in patients with HR+ HER2- metastatic breast cancer who had previously been administered endocrine therapy, compared with fulvestrant plus placebo.
“The CAPitello-291 phase 3 trial evaluates the efficacy and safety of the capivasertib-fulvestrant combination in 708 patients with HR+ HER2- advanced breast cancer previously treated with endocrine therapy versus fulvestrant plus placebo”, explained Dr. Mafalda Oliveira , a medical oncologist at Vall d’Hebron University Hospital, a researcher in the VHIO Breast Cancer Group and co-author of the study, the results of which have been published in The New England Journal of Medicine.
Risk of cancer progression or death decreased by 40%
Approximately half of HR+ HER2- breast cancers present an overactivation of the PI3K/AKT pathway, which drives the growth and metastatic capacity of the tumor and intervenes in resistance to endocrine therapy, but the researcher has assured that the The group of patients included in the new study constitutes a sample “sufficiently heterogeneous to be representative of the patients that we can find in day-to-day clinical practice”, since “among the patients recruited, a subgroup of patients was identified whose tumors had genetic alterations in the Akt pathway (in the PIK3CA, AKT1 or PTEN genes), but patients in whom no alterations in this pathway were identified in their tumors and patients whose tumors were unknown to carry the Akt pathway were also included. mutations or not.
The median progression-free survival of cancer was 7.2 months in patients with capivasertib-fulvestrant and 3.6 months with placebo-fulvestrant
In the analysis of the overall number of patients, a 40% decrease in the risk of progression or death was observed in the group of patients treated with capivasertib-fulvestrant, compared to those treated with placebo-fulvestrant. The median progression-free survival (the time between the start of treatment and the tumor growing back) was 7.2 months in patients with capivasertib-fulvestrant and 3.6 months with placebo-fulvestrant.
In the population of patients with tumors with altered Akt pathway, the reduction in the risk of progression or death was 50%, with a median progression-free survival of patients treated with the new combination of 7.3 months compared to 3.1 months with placebo-fulvestrant. Regarding adverse effects, the most frequent were rash, diarrhea, and hyperglycemia, but overall the combination was well tolerated.
“Although the clinical benefits are greater in patients with Akt alterations, we observed that in the overall population with or without alterations the combination of the two drugs is clearly superior to the current standard treatment of fulvestrant alone. In conclusion, the results of this study suggest that the capivasertib-fulvestrant combination could replace the standard treatment for these patients and change clinical practice in the short-medium term” concludes Dr. Mafalda Oliveira.
Source: Vall d’Hebron University Hospital
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