Novartis' PI3K Inhibitor Piqray: First Therapy Specifically for PIK3CA-Mutated HR+/HER2- Advanced Breast Cancer

August 15, 2020 News /BioValleyBIOON/ --Novartis(Novartis) recently announced that the anticancer drug Piqray (alpelisib) has been approved for marketing in Canada. Piqray, in combination with fulvestrant, is indicated for the treatment of postmenopausal women and men.Breast CancerPatients, specifically: those with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) locally advanced or metastatic breast cancer who have progressed after endocrine therapy and harbor PIK3CA mutations.

It is worth mentioning that,Piqray is the first and only drug specifically approved for the treatment ofTumorTreatment Approaches for Patients with Advanced Breast Cancer Harboring PIK3CA MutationsThis approval is based on the results of the pivotal Phase III SOLAR-1 clinical trial, which included 10 CanadianClinical Trialsand 10 Canadian clinical investigators. Data show that, compared with fulvestrant, treatment with Piqray plus fulvestrant willProgression-free survival was significantly doubled (median PFS: 11.0 months vs. 5.7 months)、Overall response rate (ORR) more than doubled (36% vs 16%).

Piqray is an α-specific PI3K kinase inhibitor that was approved in the United States in May 2019FDAApproved; received EU approval in June 2020, with indications identical to those approved in Canada. The launch of this drug will changeTumorTreatment Landscape for Patients with HR+/HER2- Advanced Breast Cancer Harboring PIK3CA Mutations: Providing Clinicians with a Clear Therapeutic Approach

Clinical Assistant Professor, Cumming School of Medicine, University of Calgary, Canada; Tom Baker Cancer CentreTumorDr. Jan-Willem Henning stated, “The emergence of Piqray as a new treatment option is welcome news for Canadian patients with metastatic breast cancer harboring the specific PIK3CA mutation, as it enables us to provide more therapeutic choices and deliver targeted therapy tailored to patients. This has the potential to transform our clinical practice in this field.”

Globally, 334,000 people are annuallyDiagnosisfor advanced breast cancer. PIK3CA is the most commonly mutated gene in the HR+/HER2- subtype of breast cancer, with approximately 40% of patients with HR+/HER2- breast cancer harboring this mutation. PIK3CA mutations stimulateTumorgrowth, and is associated with poor response to treatment and a very poor prognosis. Currently, the commercial companion for PIK3CA mutation testingDiagnosisAlready launched,Novartisis committed to establishing a Center of Excellence for PIK3CA mutation testing, leveraging this validatedDiagnosisTesting is more widely available to patients.

Cathy Ammendolea, Chair of the Board of Directors of the Canadian Breast Cancer Network, stated, “This is the first time that patients can receive PIK3CABiomarkertesting and receive treatment plans tailored to their specific genetic mutation types. This is an important milestone that brings new hope to Canadian patients with metastatic breast cancer, and we look forward to the positive impact it will have.”

Chemical Structure of Alpelisib (Image source: selleckchem.com)

SOLAR-1 was a randomized, double-blind, placebo-controlled Phase III study conducted in postmenopausal women and men with PIK3CA-mutated, HR+/HER2- advanced or metastatic breast cancer who had experienced disease progression during or after treatment with an aromatase inhibitor (with or without a CDK4/6 inhibitor), to evaluate the efficacy and safety of Piqray in combination with fulvestrant.

A total of 572 patients were randomized in this study, based onTumorPatients were assigned to the PIK3CA-mutant cohort (n=341) or the PIK3CA non-mutant cohort (n=231) based on tissue assessment results. Within each cohort, patients were randomized in a 1:1 ratio to receive either Piqray (300 mg once daily) plus fulvestrant (500 mg per 28-day cycle, with an additional loading dose on Day 15 of Cycle 1) or placebo plus fulvestrant. Stratification was based on the presence of visceral metastases or prior CDK4/6 inhibitor therapy. The primary endpoint was progression-free survival (PFS) in patients with PIK3CA mutations, assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1). Secondary endpoints included, but were not limited to, overall survival (OS), objective response rate (ORR), clinical benefit rate, health-related quality of life, efficacy in the PIK3CA non-mutant cohort, safety, and tolerability.

The results demonstrated that the study met its primary endpoint: in patients with PIK3CA-mutated, HR+/HER2- advanced breast cancer, treatment with Piqray in combination with fulvestrant nearly doubled progression-free survival (PFS) compared with fulvestrant alone (median PFS: 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). In terms of overall response rate (ORR), the Piqray plus fulvestrant group achieved more than twice the ORR of the fulvestrant group (36% vs. 16%). Subgroup analysis of PFS showed consistent efficacy of Piqray regardless of the presence of lung or liver metastases. In patients without PIK3CA mutations, the improvement in PFS with the combination of Piqray and fulvestrant was not significant.

In terms of safety, most adverse events in the study were mild to moderate and generally manageable through dose adjustments and medical management. Among these, the most common Grade 3/4 events (≥7%) were hyperglycemia (39.1%), rash (19.4%), elevated gamma-glutamyl transferase (12.0%), lymphopenia (9.2%), diarrhea (7.0%), and elevated lipase (7.0%). No patients developedDiabetes. Currently, the SOLAR-1 study is still ongoing to evaluate overall survival (OS) and other secondary endpoints. (Bioon.com)

Original source: PIQRAY isapproved and now available in Canada as the first and only treatment specifically for patients with a PIK3CA mutation in HR-positive, HER2-negative advanced breast cancer