Novartis PI3K Inhibitor Piqray Demonstrates Clinical Benefit Regardless of Key Biomarkers in HR+/HER2- Metastatic Breast Cancer

News on June 10, 2022 /BioValleyBIOON/ -- Novartis recently at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting Announced the Results of an Exploratory Retrospective Biomarker Analysis. The analysis found that,In tumors carrying PIK3CA mutations, different genetic mutation profiles do not affect theirBreast CancerClinical Benefits of the Innovative Drug Piqray (Alpelisib) Combined with Fulvestrant in HR+/HER2- Advanced or Metastatic Breast Cancer (mBC) Patients with Disease Progression After Endocrine Therapy.

Piqray is the only approved treatment specifically for HR+/HER2-mBC patients with PIK3CA mutations, which are key oncogenic drivers of the disease.A retrospective analysis of the Phase 3 SOLAR-1 study data found,Regardless of the genetic alterations in the majority of biomarkers (including the ESR1 gene and genes associated with CDK4/6 inhibitor resistance), the clinical benefits of Piqray plus fulvestrant combination therapy are maintained.

Detailed Results of the ASCO SOLAR-1 Biomarker Retrospective Analysis Are as Follows:(1) In patients carrying ESR1 gene alterations, the median progression-free survival (mPFS) was 12.0 months for those treated with Piqray plus fulvestrant, compared to 6.5 months for those receiving fulvestrant alone. (2) Even in patients with FGFR1 and FGFR2 gene alterations associated with CDK4/6 inhibitor resistance, the combination of Piqray and fulvestrant still demonstrated clinical benefit, with mPFS of 12.7 months and 9.6 months, respectively, versus 3.8 months and 2.8 months for fulvestrant alone. (3) The clinical benefit of Piqray plus fulvestrant was also observed regardless of other gene alterations, including: TP53, CCND1, MAP3K1, ARID1A, genes in the MAPK pathway, and genes associated with CDK4/6 inhibitor resistance (such as RB1).

Real-world evidence (RWE) supports the effectiveness of Piqray in PIK3CA-mutated tumors: A real-world retrospective analysis showed that, in 157 casesHR+/HER2- Advanced or Metastatic Breast Cancer Patients Treated with Piqray Plus Fulvestrant Achieved Clinical Benefit, Even in Some Patients Previously Treated with Fulvestrant, Confirming Oncogenic Dependence on PIK3CA MutationsIn this analysis, prior fulvestrant treatments included: CDK4/6 inhibitor + fulvestrant (74.5%), fulvestrant monotherapy (33.8%), non-CDK4/6 inhibitor + fulvestrant (21.0%).

Dejan Juric, MD, Director of the Henri and Belinda Termeer Center for Targeted Therapies at Massachusetts General Hospital, stated: "This analysis evaluates the clinical benefits of Piqray plus fulvestrant combination therapy in HR+/HER2- advanced breast cancer tumors with various genetic alterations, confirming the importance of selectively targeting the main oncogenic driver PIK3CA in these tumors using alpelisib."

Novartis US Oncology Executive Vice President Reshema Kemps-Polanco stated: "PIK3CA mutations affect approximately 40% of HR+/HER2- subtype patients and are a known oncogenic driver in metastatic breast cancer, associated with resistance to endocrine therapy and an overall poorer prognosis. Therefore, physicians must base their decisions on ASCO and NCCN guidelines."Guideline"Pre-testing for PIK3CA mutations and Piqray treatment."

Chemical Structure of Alpelisib (Source: selleckchem.com)

Globally, approximately 362,000 people areDiagnosisFor metastatic breast cancer (mBC). Approximately 40% of patients with the HR+/HER2- subtype have PIK3CA mutations in their tumors, which stimulate tumor growth and are associated with poor treatment response and dismal prognosis.

Piqray is an α-specific PI3K kinase inhibitor., which was approved by the United States in May 2019 and by the European Union in July 2020, is used to treat postmenopausal women and male breast cancer patients, specifically: those who have experienced disease progression during or after endocrine therapy, carry the PIK3CA mutation, and have HR+/HER2- advanced or metastatic breast cancer.

Piqray is the first and only treatment specifically approved for patients with advanced breast cancer whose tumors harbor PIK3CA mutations. To date, the drug has been approved in more than 70 countries. The availability of this drug has transformed the treatment landscape for patients with HR+/HER2- advanced breast cancer carrying PIK3CA mutations, providing clinicians with a definitive treatment option. (Bioon.com)

Source of the original text:New Novartis data show Piqray® effectiveness across key biomarkers in patients with HR+/HER2- metastatic breast cancer