On June 3, 2022 Novartis reported results of an exploratory retrospective biomarker analysis finding that different genetic mutation profiles in tumors harboring PIK3CA mutation did not affect treatment benefit with Piqray (alpelisib) plus fulvestrant in patients with hormone receptor-positive, human epidermal growth factor receptor-2 negative (HR+/HER2-) advanced or metastatic breast cancer following progression on or after an endocrine-based regimen (Press release, Novartis, JUN 3, 2022, View Source [SID1234634694]). Selected as an oral presentation at the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (Abstract #1006), the retrospective analysis of data from the Phase III SOLAR-1 study found that the clinical benefit of the Piqray and fulvestrant combination was maintained regardless of genetic alterations in most biomarkers, including ESR1 and genes implicated in resistance to CDK4/6 inhibitors1.

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"This analysis evaluating alpelisib and fulvestrant across HR+/HER2- advanced breast cancer tumors with different genetic alterations confirms the importance of using alpelisib to selectively target PIK3CA as a major oncogenic driver in these tumors," said Dejan Juric, MD, Director, Termeer Center for Target Therapies, Mass General Cancer Center in Boston.

"PIK3CA mutations affect approximately 40% of those with the HR+/HER2- subtype and are known oncogenic drivers of metastatic breast cancer, associated with endocrine resistance and an overall worse prognosis—so it’s critical for physicians to test and treat with Piqray for patients with PIK3CA mutations upfront consistent with ASCO (Free ASCO Whitepaper) and NCCN guidelines," said Reshema Kemps-Polanco, Executive Vice President, US Oncology at Novartis.

Highlights from the SOLAR-1 biomarker retrospective analysis at ASCO (Free ASCO Whitepaper)

Patients with ESR1 gene alterations achieved 12.0 months of median progression-free survival (mPFS) when treated with Piqray and fulvestrant compared to 6.5 months for those treated with fulvestrant alone1.
Even patients with FGFR1 and FGFR2 gene alterations, which have been associated with resistance to CDK4/6 inhibitors, had benefit when treated with Piqray plus fulvestrant (12.7 months and 9.6 months mPFS, respectively), compared to those treated with fulvestrant alone (3.8 months and 2.8 months mPFS, respectively)1.
The benefit seen with the Piqray and fulvestrant combination was independent of additional genetic alterations, including TP53, CCND1, MAP3K1 and ARID1A; genes in the MAPK pathway, genes implicated in CDK4/6 inhibitor resistance such as RB11.
Real-world evidence supports effectiveness of Piqray in tumors with PIK3CA mutation
A real-world retrospective analysis (Abstract #1055) showed clinical benefit for 157 patients with HR+/HER2- advanced or metastatic breast cancer with PIK3CA genetic mutation following treatment with Piqray plus fulvestrant, even when exposed to prior treatment with fulvestrant, confirming the oncogenic dependence of the tumor on the PIK3CA mutation2. In the analysis, prior fulvestrant treatment included CDK4/6 inhibior plus fulvestrant (74.5%), fulvestrant alone (33.8%), and non-CDK4/6 inhibitor plus fulvestrant (21.0%)2.

About PIK3CA-mutated Breast Cancer
An estimated 361,826 people are diagnosed with metastatic breast cancer worldwide each year, and approximately 40% of those with HR+/HER2- subtype have tumors that harbor a PIK3CA mutation, which is associated with a poor prognosis6-7.

About Piqray (alpelisib)
Piqray is a kinase inhibitor developed for use in combination with fulvestrant for the treatment of postmenopausal women, and men, with HR+/HER2-, PIK3CA-mutated, advanced or metastatic breast cancer following progression on or after endocrine-based regimen3. Piqray is approved in over 70 countries, including the US6. In the European member states, Piqray plus fulvestrant is approved after disease progression following endocrine therapy as monotherapy8.

Novartis is continuing to reimagine cancer with additional trials of Piqray. To complement the SOLAR-1 study, EPIK-B5, a large Phase III clinical trial is conducted with Piqray in combination with fulvestrant following treatment with a CDK4/6 inhibitor and aromatase inhibitor9. Novartis is also studying the potential of Piqray in triple-negative breast cancer (TNBC) in the EPIK-B3 Phase III clinical trial, in advanced HER2+ breast cancer in the EPIK-B2 Phase III clinical trial and in ovarian cancer in the EPIK-O Phase III clinical trial10-12.