The combination of alpelisib and fulvestrant maintained a tolerable safety profile for patients with PIK3CA-mutated, hormone receptor–positive, HER2-negative advanced breast cancer who progressed after previous treatment with a CDK4/6 inhibitor.
Alpelisib (Piqray) plus fulvestrant (Faslodex) produced activity while maintaining a tolerable safety profile for patients with PIK3CA-mutated, hormone receptor–positive, HER2-negative advanced breast cancer who progressed after previous therapy with a CDK4/6 inhibitor plus an aromatase inhibitor, according to data published in Lancet Oncology.
The ongoing, multicenter, open-label, phase 2 BYLieve trial (NCT03056755) assessed both safety and activity of the combination of alpelisib plus either letrozole (Femara) or fulvestrant to treat patients with this type of HER2-negative advanced breast cancer.
“BYLieve shows that alpelisib plus fulvestrant is an active treatment option with manageable tolerability for patients with hormone receptor–positive, HER2-negative, PIK3CA-mutated advanced breast cancer in the post-CDK4/6 inhibitor plus aromatase inhibitor setting,” wrote the investigators. “The improved safety outcomes observed in BYLieve support that previous CDK4/6 inhibitor exposure is unlikely to affect the safety profile of alpelisib plus fulvestrant, and that adverse events are generally manageable with current guidance.”
The research enrolled 127 patients between August 14, 2017 and December 17, 2019 with a minimum of 6 months of follow-up. Specifically, 121 of those patients had a centrally confirmed PIK3CA mutation. Median follow-up at the data cutoff was 11.7 months.
The patients eligible and included in the study cohort received oral alpelisib 300 mg/day plus fulvestrant 500 mg intramuscularly on day 1 and day 15 of a 28-day cycle, with the day 15 treatment occurring only during cycle 1.
Treatment was ongoing for 26% of the patient population at the data cutoff point. Both progressive disease (64 patients) and adverse events (18 patients) were cited as the main reasons for discontinuing treatment.
Local investigator assessment at 6 months found 50.4% of patients were alive without disease progression (95% CI, 41.2%-59.6%). More, median progression-free survival (PFS) was 7.3 months (95% CI, 5.6-8.3), with a 6-month PFS rate of 54% (95% CI, 44%-63%).
The median overall survival for patients was 17.3 months (95% CI, 17.2-20.7). Twenty-five deaths were reported, and 17% of patients (95% CI, 11%-25%) achieved an overall response. The median duration of response was 6.6 months (95% CI, 4.3-not estimable).
Common grade 3 or worse adverse events (AEs) included hyperglycemia (28%), rash (9%), and rash maculopapular (9%). Twenty-six percent of patients experienced serious AEs, with no treatment-related deaths reported.
“To our knowledge, BYLieve is the first, prospective clinical study to examine the use of alpelisib plus fulvestrant for hormone receptor–positive, HER2-negative, PIK3CA-mutated advanced breast cancer solely in the post-CDK4/6 inhibitor setting,” explained the investigative team.
Eligible patients were aged 18 years or older, had an ECOG performance status of 2 or less, and had 2 or fewer prior anticancer treatments and 1 or fewer chemotherapy treatment.
Because no comparison group existed in this trial, the inability for cross-comparisons limited the study’s data. More, even though the trial divided the population into 3 cohorts, data for cohorts 2 and 3 remain unknown. Further understanding of the combination’s activity will be known when those cohorts are fully reported.
“Our results support the use of alpelisib plus fulvestrant for treatment of hormone receptor-positive, HER2-negative, PIK3CA-mutated advanced breast cancer in the post-CDK4/6 inhibitor setting,” wrote the investigators.
Rugo HS, Lerebours F, Ciruelos E, et al. Alpelisib plus fulvestrant in PIK3CA-mutated, hormone receptor-positive advanced breast cancer after a CDK4/6 inhibitor (BYLieve): one cohort of a phase 2, multicentre, open-label, non-comparative study. Lancet Oncol. 2021;22(4):489-498. doi:10.1016/S1470-2045(21)00034-6