Writing
The magazine The Lancet Oncology has published this Wednesday the conclusions of the study led by the VHIO researcher and oncologist at the Vall d’Hebron University Hospital Mafalda Oliveirawhich analyzes the results reported by patients with locally advanced or metastatic breast cancer con receptor hormonal RH+ y HR2- alterations in the Akt signaling pathway, treated with the oral drug capivasertibdeveloped by AstraZeneca, in combination with fulvestrant.
The published data conclude that the time until deterioration of health and quality of life in patients treated with the new combination is prolonged compared to those patients treated only with fulvestrant, with a median 24.9 versus 12 months. These results on quality of life of the CAPItello-291 studioare part of a phase 3 clinical trial that has already been published in the journal New England Journal of Medicinewhich laid the groundwork for the European Medicines Agency (EMA) to lay the groundwork for the approval of capivasertib in combination with fulvestrant for these patients.
The time to deterioration in quality of life and health in patients treated with capivasertib and fulvestrant reached a median of 24.9 months versus 12 in those who received only fulvestrant.
“The findings of this exploratory analysis of patient-reported outcomes from the CAPItello-291 study, together with the previously demonstrated clinical efficacy and manageable safety profile, further support the positive benefit-risk profile“, Dr. Mafalda Oliveira says: Approximately 70% of breast tumors are of the RH+ HER2 – type. Alterations in the Akt pathway (mutations in PIK3CA, mutations in AKT1 and genomic alterations in PTEN) affect about 50% of patients with advanced RH+ breast cancer.
In metastatic RH+ HER2- tumors, the first line of standard treatment is CDK4/6 inhibitors in combination with endocrine therapy. “However, when the tumor progresses to this line of treatment, the management of these patients continues to be a clinical challenge.”explains Dr. Oliveira. Current treatment options for these patients include fulvestrant, an intramuscular drug that selectively degrades the estrogen hormone receptor, as monotherapy or in combination with other drugs.
Dr. Oliveira: “The approval of this new Akt inhibitor is good news for approximately half of patients with HR+ breast cancer in Europe”
“The approval of this new Akt inhibitor is good news for the approximately half of HR+ breast cancer patients in Europe who have tumors with these biomarkers, and It is important for physicians to test and identify eligible patients that can benefit from this combination” says the researcher.
The CAPitello-291 phase 3 trial evaluated 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. The lead author of the paper notes that among the recruited patients, a subgroup of patients was identified whose tumors had genetic alterations in the Akt pathway, patients in whom no alterations in this pathway were identified in their tumors, and patients for whom it was unknown whether the tumor carried the mutations or not. “In short, The sample is sufficiently heterogeneous to be representative of the patients we can find in our daily clinical practice”added Oliveira.
In the population of patients with tumors with the altered Akt pathway, the reduction in the risk of progression or death was 50%
In it analysis of the global of patients, a was observed 40% reduction in risk of progression or death in the capivasertib-fulvestrant group compared with those treated with placebo-fulvestrant. The median progression-free survival was 7.2 months in patients on capivasertib-fulvestrant and 3.6 months in patients on placebo-fulvestrant.
In the population of patients with tumors with the altered Akt pathwaythe reduction in risk of progression or death was 50%with a median progression-free survival of 7.3 months for patients treated with the new combination versus 3.1 months with placebo-fulvestrant. The most common adverse effects were rash, diarrhea and hyperglycemia, but overall the combination was well tolerated.
Regulatory applications are currently under review in China and several other countries. Similar indications for capivasertib, in combination with fulvestrant, are already approved in the United States, Japan and several other countries based on the CAPItello-291 trial.
