Data Show PIK3CA Mutation Does Not Affect Breast Cancer Treatment Benefit With Alpelisib

Novartis has announced the results of an exploratory retrospective biomarker analysis showing that different genetic mutation profiles in tumors harboring PIK3CA mutation did not affect treatment benefit with alpelisib (Piqray) combined with fulvestrant in individuals 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.

The respective analysis will be presented as an oral presentation at the 2022 American Society of Clinical Oncology Annual Meeting.

Investigators of the phase 3 SOLAR-1 study found that the clinical benefit of alpelisib combined with fulvestrant was maintained, regardless of genetic alteration, in most biomarkers, including ESR1 and genes implicated in resistance to CDK4/6 inhibitors.

“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,” Dejan Juric, MD, director of the Termeer Center for Target Therapies at Mass General Cancer Center in Boston, Massachusetts, said in a statement.

Investigators found that individuals with ESR1 gene alterations achieved approximately 12 months of median progression-free survival (mPFS) when treated with alpelisib combined with fulvestrant compared with approximately 6.5 months for those treated with fulvestrant alone.

Additionally, those with FGFR1 and FGFR2 gene alterations, which are associated with resistance to CDK4.6 inhibitors, gained a benefit when treated with alpelisib combined with fulvestrant at 12.7 months and 9.6 months mPFS, respectively, compared to those treated with fulvestrant alone at 3.8 and 2.8 months mPFS, respectively.

The benefit with alpelisib combined with fulvestrant was independent of additional genetic alterations, including TP53, CCND1, MAP3K1 and ARID1A; genes in the MAPK pathway, and genes implicated in CDK4/6 inhibitor resistance such as RB11, according to the study investigators.

“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 [alpelisib] for patients with PIK3CA mutations upfront consistent with ASCO and NCCN guidelines,” Reshema Kemps-Polanco, executive vice president of US Oncology at Novartis, said in the statement.

A real-world analysis showed clinical benefit for 157 individuals with HR+/HER2- advanced or metastatic breast cancer with PIK3CA genetic mutation after treatment with alpelisib combined with fulvestrant, which confirmed the oncogenic dependence of the tumor on the PIK3CA mutation.

Additionally, prior fulvestrant treatment included CDK4/6 inhibitor plus fulvestrant at 74.5%, fulvestrant alone at 33.8%, and non-CDK4/6 inhibitor plus fulvestrant at 21%, investigators reported.

Alpelisib is a kinase inhibitor that is developed for use in combination with fulvestrant for the treatment of women who are postmenopausal and men who have HR+/HER2-, PIK3CA-mutated, advanced or metastatic breast cancer following progression on or after endocrine-based regimen.

In the United States, alpelisib is approved in combination with fulvestrant, to treat postmenopausal women, as well as men, with HR+/HER2-, PIK3CA-mutated, advanced or metastatic breast cancer following progression on or after an endocrine-based regimen.

Reference

New Novartis data show Piqray effectiveness across key biomarkers in patients with HR+/HER2- metastatic breast cancer. Syneos Health. News release. June 3, 2022. Accessed June 3, 2022. Email.