EU Approval Details of Piqray
Novartis recently announced that the European Commission (EC) has approved Piqray (alpelisib) in combination with fulvestrant for the treatment of postmenopausal women and men with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) locally advanced or metastatic breast cancer with a PIK3CA mutation, whose disease has progressed following endocrine therapy alone.
Key Advantages and Global Approval Status of Piqray
Piqray is the first and only therapy specifically approved for patients with advanced breast cancer harboring a PIK3CA mutation. Data from the phase III SOLAR-1 trial demonstrated that Piqray plus fulvestrant nearly doubled progression-free survival (median PFS: 11.0 months vs 5.7 months) and more than doubled the overall response rate (ORR: 36% vs 16%) compared with fulvestrant alone.
An α-specific PI3K kinase inhibitor, Piqray was approved by the U.S. FDA in May 2019 for the same indication. To date, the drug has been approved in 48 countries. Its launch will reshape the treatment landscape for patients with PIK3CA-mutated HR+/HER2- advanced breast cancer and provide clinicians with a well-defined therapeutic option.
Comment from Novartis Oncology Europe
Kees Roks, Head of Novartis Oncology Europe, stated: “Piqray represents an important new therapy for patients with PIK3CA-mutated HR+/HER2- advanced breast cancer. Understanding PIK3CA status enables physicians to better tailor personalized frontline treatment plans. Piqray brings new hope to patients with PIK3CA-mutated advanced breast cancer, who typically face a poorer overall prognosis.”
Introduction to the Phase III SOLAR-1 Trial
Trial Design
SOLAR-1 is a randomized, double-blind, placebo-controlled phase III study evaluating the efficacy and safety of Piqray plus fulvestrant in postmenopausal women and men with PIK3CA-mutated, HR+/HER2- advanced or metastatic breast cancer whose disease progressed during or after treatment with an aromatase inhibitor (with or without a CDK4/6 inhibitor).
A total of 572 patients were randomized and assigned to the PIK3CA-mutated cohort (n=341) or PIK3CA non-mutated cohort (n=231) based on tumor tissue assessment. Within each cohort, patients were randomized 1:1 to receive Piqray (300 mg once daily) plus fulvestrant (500 mg on day 1 and day 15 of cycle 1, then day 1 of each 28-day cycle) or placebo plus fulvestrant. Stratification factors were visceral metastasis and prior CDK4/6 inhibitor therapy.
Trial Endpoints
The primary endpoint was progression-free survival (PFS) in patients with PIK3CA mutation per RECIST 1.1. Secondary endpoints included, but were not limited to, overall survival (OS), ORR, clinical benefit rate, health-related quality of life, efficacy in the PIK3CA non-mutant cohort, safety, and tolerability.
Trial Results
Results showed that the study met its primary endpoint: in patients with PIK3CA-mutated HR+/HER2- advanced breast cancer, Piqray plus fulvestrant nearly doubled PFS (median 11.0 months vs 5.7 months) and significantly reduced the risk of disease progression or death by 35% (HR=0.65, 95% CI: 0.50–0.85; p<0.001) compared with fulvestrant alone. The ORR was more than two times higher with Piqray plus fulvestrant than with fulvestrant alone (36% vs 16%).
Subgroup analyses of PFS showed consistent efficacy regardless of lung/liver metastasis. In patients without PIK3CA mutation, Piqray plus fulvestrant did not show a meaningful improvement in PFS.
Safety Profile of Piqray
Regarding safety, most adverse events in the study were mild to moderate and generally manageable with dose modifications and medical management. The most common grade 3/4 events (≥7%) were hyperglycemia (39.1%), rash (19.4%), gamma-glutamyl transferase increased (12.0%), lymphocytes decreased (9.2%), diarrhea (7.0%), and lipase increased (7.0%). No patients developed diabetes due to transient hyperglycemia.
The SOLAR-1 study remains ongoing to evaluate OS and other secondary endpoints.
