To determine whether treatment with alpelisib plus fulvestrant prolonged progression-free
survival (PFS) compared to fulvestrant and placebo in men and postmenopausal women with
hormone receptor positive (HR+), human epidermal growth factor receptor-2 (HER2)-negative
advanced breast cancer, who received prior treatment with an aromatase Inhibitor (AI)
either as (neo)adjuvant or for advanced disease.
Additional locations may be listed on ClinicalTrials.gov for NCT02437318.
See trial information on ClinicalTrials.gov for a list of participating sites.
This was a randomized, double-blind, placebo-controlled, international multicenter Phase
III study that evaluated the efficacy and safety of treatment with alpelisib plus
fulvestrant versus placebo plus fulvestrant in men and postmenopausal women with
HR-positive, HER2-negative advanced breast cancer which had progressed on or after AI
treatment.
Subjects were allocated to either the PIK3CA mutant or PIK3CA non-mutant cohort, based on
central testing of hotspot-mutations in tumor tissue. Subjects with unknown results were
not eligible. Within each cohort, subjects were randomized in a 1:1 ratio to receive
either alpelisib 300 mg orally once daily (q.d.), in combination with fulvestrant 500 mg
intramuscular (i.m.) on Days 1 and 15 of Cycle 1 and Day 1 of a 28-day cycle thereafter,
or placebo daily in combination with fulvestrant 500 mg following the same treatment
regimen.
Subjects were treated until disease progression, unacceptable toxicity, death, or
discontinuation from the study treatment for any other reason. All subjects who
discontinued study treatment were followed for safety, until 30 days after last study
treatment administration, except in the case of death, loss to follow-up, or withdrawal
of consent.
Subjects who discontinued study treatment for reasons other than disease progression or
withdrawal of consent, were followed until disease progression, death, withdrawal of
consent, loss to follow-up, or subject/guardian decision (post-treatment efficacy
follow-up).
Finally, all subjects were followed for survival after discontinuation of study treatment
and tumor evaluations until the subject's death, loss to follow-up, or withdrawal of
consent for survival follow-up (post-treatment survival follow-up)
Lead OrganizationNovartis Pharmaceuticals Corporation