Late-stage study of Novartis' PI3K inhibitor BYL719 in breast cancer hits main goal

Novartis said Thursday that a Phase III study of BYL719, also known as alpelisib, in certain postmenopausal women and men with hormone-receptor positive, HER2-negative PIK3CA-mutant advanced or metastatic breast cancer met its primary endpoint showing an improvement in progression-free survival (PFS). Samit Hirawat, head of oncology global drug development, remarked "we are encouraged by the results…and look forward to…starting discussions with health authorities worldwide."

The SOLAR-1 trial randomised 572 postmenopausal women and men with PIK3CA-mutated hormone-receptor positive, HER2-negative advanced or metastatic breast cancer that progressed on or following prior aromatase inhibitor treatment with or without a CDK4/6 inhibitor to receive BYL719 or placebo, both in combination with AstraZeneca's Faslodex (fulvestrant). Novartis noted that patients were allocated based on tumour tissue assessment to either a PIK3CA-mutant cohort or a PIK3CA non-mutant cohort, with the study's main goal being evaluated in the former group.

Novartis indicated that the study will continue to assess data for secondary endpoints, which include overall survival, overall response rate, clinical benefit rate, health-related quality of life, efficacy in PIK3CA non-mutant cohort, safety and tolerability. The drugmaker added that full results from the trial will be submitted to an upcoming medical meeting.

Novartis noted that there are currently no approved PI3K inhibitors for hormone-receptor positive advanced breast cancer, with approximately 40 percent of these patients having PIK3CA mutations. "BYL719 is the only alpha-specific PI3K inhibitor and the first one to show potential increased benefit and acceptable tolerability for patients," commented Hirawat.

Analysts suggest that BYL719 could dominate the treatment of patients with hormone-receptor positive, HER2-negative breast cancer who failed previous treatments, with Bruno Bulic of Baader Helvea estimating "peak sales potential at $1.9 billion." Bulic also lifted the drug's "probability of success to 80 percent." For related analysis, see ViewPoints: Novartis previews a breast cancer breakthrough.

However, similar drugs have faced recent setbacks, with Roche disclosing in June that it will not seek FDA approval of the PI3K inhibitor taselisib based on results of a Phase III study in women with advanced breast cancer. Data from the SANDPIPER trial showed that although taselisib extended PFS versus placebo, Roche's drug was associated with more severe side effects, forcing 17 percent of women to stop treatment early.

Meanwhile, last month, Novartis offloaded rights to the oral pan-PI3K inhibitor buparlisib to Adlai Nortye Biopharma. Researchers had previously concluded that findings from the BELLE-3 study of buparlisib in postmenopausal women with hormone-receptor positive, HER2-negative, locally advanced or metastatic breast cancer, who had relapsed on or after endocrine therapy and mTOR inhibitors, do not support further development.

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