The Food and Drug Administration approved alpelisib in combination with fulvestrant for postmenopausal women, and men, with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, PIK3CA-mutated, advanced or metastatic breast cancer as detected by an FDA-approved test following progression on or after an endocrine-based regimen.

Approval was based on SOLAR-1 (NCT02437318), a phase 3, randomised, double-blind, placebo-controlled trial of alpelisib plus fulvestrant versus placebo plus fulvestrant in 572 patients including postmenopausal women, and men, with HR-positive, HER2-negative, advanced or metastatic breast cancer whose disease had progressed or on or after receiving an aromatase inhibitor.

The primary endpoint was investigator-assessed progression-free survival (PFS) in the cohort with a PIK3CA mutation.

The estimated median PFS by investigator assessment in the alpelisib plus fulvestrant arm was 11.0 months (95% CI: 7.5, 14.5) compared with 5.7 months (95% CI: 3.7, 7.4) in the placebo plus fulvestrant arm (HR 0.65; 95% CI: 0.50, 0.85; p=0.001).

Overall survival data were not mature at the time of analysis.

No PFS benefit was observed in patients whose tumours did not have a PIK3CA mutation (HR = 0.85; 95% CI: 0.58, 1.25).

The most common adverse reactions including laboratory abnormalities on the alpelisib plus fulvestrant arm were increased glucose, increased creatinine, diarrhea, rash, decreased lymphocyte count, increased gamma glutamyl transferase, nausea, increased alanine aminotransferase, fatigue, decreased hemoglobin, increased lipase, decreased appetite, stomatitis, vomiting, decreased weight, decreased calcium, decreased glucose, prolonged activated partial thromboplastin time (aPTT), and alopecia.

The recommended alpelisib dose is 300 mg (two 150 mg film-coated tablets) taken orally, once daily, with food. When given with alpelisib, the recommended dose of fulvestrant is 500 mg administered intramuscularly on days 1, 15, and 29, and once monthly thereafter.

Source: The Food and Drug Administration (FDA)