In 2018, France granted the use of alpelisib, a PIK3CA inhibitor, in combination with fulvestrant, in pretreated patients with PIK3CA-mutant, HR-positive/HER2-negative advanced breast cancer. Through an early access program, researchers assessed the efficacy and safety of alpelisib plus fulvestrant in patients who had been treated with a minimum of 2 systemic therapies, including an aromatase inhibitor and a CDK4/6 inhibitor.
This retrospective, real-world study enrolled 209 women who participated in the early access study between November 2018 and October 2020. Data from 209 women with at least 1 previous systemic treatment were collected from 10 treatment clinics across France. Investigators aimed to evaluate the efficacy and safety of alpelisib/fulvestrant combination therapy in patients who had been previously treated with a CDK4/6 inhibitor.
Participants had also received a median of 4 previous systemic treatments for advanced breast cancer, including CDK4/6 inhibitors (98.8%), chemotherapy (76.4%), fulvestrant (78%; alone or in combination), and everolimus (55.5%). The primary end point was progression-free survival (PFS), and secondary end points included response rate and safety. Patients followed up for a median of 7 months with a median PFS of 4.9 months. An objective response was observed in 35.4% of patients.
Although the cohort consisted of patients who had long-term disease control with everolimus, prior exposure to everolimus did not affect PFS. Performance status <3 and prior treatment with fulvestrant were significantly associated with longer PFS. Discontinuation of alpelisib occurred in some patients due to grade 3 or 4 adverse events, including hyperglycemia (11.9%), skin rash (8.1%), diarrhea (4.8%), and fatigue (1.9%).
Alpelisib plus fulvestrant demonstrated clinically relevant efficacy that was not affected by pretreatment with everolimus or fulvestrant in the French breast cancer patients. The study indicates alpelisib plus fulvestrant combination therapy improves PFS within this population of cancer patients. The researchers suggest that potential investigations should evaluate an optimal treatment sequence for PI3KCA/mTOR inhibitors in patients with PIK3CA-mutant HR-positive/HER2-negative advanced breast cancer.
Source: Bello D, Bertucci A, De La Motte Rouge T, et al. Alpelisib and fulvestrant efficacy in HR-positive HER2-negative PIK3CA-mutant advanced breast cancer: data from the French early access program. American Society of Clinical Oncology Virtual Meeting; June 4-8, 2021. Abstract 1064.