The European Commission has approved Novartis‘s Piqray (alpelisib) in combination with Faslodex (fulvestrant) for the treatment of advanced or metastatic breast cancer that is hormone receptor-positive and human epidermal growth factor receptor-2-negative (HR+/HER2-) and harbors a PIK3CA mutation.
The approval, which follows a recent positive opinion from the European Medicine Agency’s Committee for Medicinal Products for Human Use, covers men and postmenopausal women who have experienced disease progression following endocrine therapy as a singular therapy.
“Piqray is an important new therapy for HR+/HER2- advanced breast cancer patients whose tumors have a PIK3CA mutation, and we look forward to making it available in countries across Europe,” Kees Roks, head region Europe at Novartis Oncology, said in a press release.
More than a third of HR+/HER2- breast cancers harbor a mutation in the gene PIK3CA. These mutations lead to increased activity in molecular pathways that drive cells to grow excessively, resulting in tumor growth and progression. Piquray works by disrupting these molecular pathways, ultimately working against PIK3CA mutation-driven tumor growth.
Because of its mechanism of action, Piqray is only recommended for treating tumors with PIK3CA mutations, which can be detected in tests of the blood or tumor tissue.
“Knowledge of PIK3CA status can better equip doctors as they develop a personalized upfront treatment plan for patients,” said Roks.
The combination of Piqray with Faslodex — a breast cancer treatment that works by blocking cancer-promoting estrogen signaling — was recently approved by the U.S. Food and Drug Administration. The agency also approved a companion test to identify PIK3CA mutations suitable to Piqray treatment.
Both EU and U.S. approvals of the Piqray-Faslodex combo were based on data from the Novartis-funded Phase 3 clinical trial SOLAR-1 (NCT02437318), in which 341 people with PIK3CA-mutated breast cancer were randomly assigned to treatment with either Faslodex and Piqray, or Faslodex and a placebo. Results from the trial were published in The New England Journal of Medicine.
Progression-free survival — the length of time participants survived without evidence of tumor growth, which was used as the study’s primary measurement of treatment efficacy — was nearly twice as long in the group given Piqray, compared to the one that got the placebo (11 vs. 5.7 months), a statistically significant difference.
The overall response rate — defined as the proportion of participants who experience at least a 30% reduction in overall tumor size — was higher in the group given Piqray (35.7% vs. 16.2%, excluding participants without measurable disease).
High-grade side effects that were more common in the group given Piqray included high blood sugar (36.6% vs. 0.7%), rash (9.9% vs. 0.3%), and diarrhea (6.7% vs. 0.3%).
“Piqray offers new hope for advanced breast cancer patients with a PIK3CA mutation, who typically face a worse overall prognosis,” Roks said.