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Novartis Seeks FDA OK for Drug With Favorable Phase III Results in PIK3CA-Mutated Breast Cancer

NEW YORK (GenomeWeb) – Novartis has filed a new drug application with the US Food and Drug Administration for its investigational drug alpelisib — an alpha-specific PI3 kinase inhibitor that shows promise for treating hormone receptor-positive, HER2-negative advanced breast cancers with PIK3CA mutations.

A spokesman for the company noted that the firm expects a decision from the regulator on BYL719 (alpelisib) in the second half of this year. Novartis is also teaming up with Qiagen to develop "flexible companion diagnostic solutions" for identifying PIK3CA mutations in circulating tumor DNA or tumor samples from breast cancer patients — a clinical development program that Qiagen announced in December.

In a Novartis-funded, randomized, Phase III clinical trial outlined in the New England Journal of Medicine today, researchers from Massachusetts General Hospital, the Gustave Roussy Institute, and other SOLAR-1 clinical trial sites saw extended progression-free survival for individuals with PIK3CA-mutated, HR-positive, HER2-negative breast tumors treated with alpelisib in combination with the hormone receptor drug fulvestrant (Faslodex) from AstraZeneca.

The team looked at progression-free survival in 572 individuals with advanced breast cancer who were randomized to receive alpelisib-fulvestrant treatment or placebo-fulvestrant treatment — a cohort that included 341 cases with PIK3CA-mutated tumors. As secondary outcomes, the investigators also considered the overall response and safety of alpelisib-fulvestrant treatment in the individuals with PIK3CA mutations in their tumors.

The researchers found that alpelisib-fulvestrant-treated patients with PIK3CA-mutated tumors had 11 months of progression-free survival, on average, over 20 months of average follow up time. Progression-free survival came in at an average of just 5.7 months in the placebo-fulvestrant-treated PIK3CA-mutated group.

They noted that patients without PIK3CA mutations also had slightly longer progression-free survival times when alpelisib was added to fulvestrant treatment, though that improvement did not reach clinical significance.

Alpelisib's safety profile appeared to be on par with that reported in the past, the team reported. The drug was associated with a rise in adverse events such as hyperglycemia, rash, and diarrhea compared with the placebo.

These and other findings presented in the paper "validate PIK3CA as an important treatment target" in individuals with PIK3CA-mutated, HR-positive, HER2-negative advanced breast cancer, according to co-corresponding authors Dejan Juric at MGH. Fabrice Andre at the Gustave Roussy Institute, and their colleagues.

They pointed to the potential benefits of incorporating an alpha-specific PI3K inhibitor into the standard treatment protocols for these patients and noted that the risk of progression appeared to be particularly reduced for the PIK3CA, HR-positive, HER2-negative cases that had already progressed on or after a prior treatment. 

The MGH's Juric presented similar SOLAR-1 results at the San Antonio Breast Cancer Symposium in December, where he also discussed results of early circulating tumor DNA analyses on the SOLAR-1 patients. The team did not include its analysis of progression-free survival analysis in the context of ctDNA in the NEJM study. Likewise, overall survival data was not yet reported.

Novartis is reportedly discussing the SOLAR-1 data with health authorities around the world, according to a company spokesman and has submitted a marketing authorization application to the European Medicines Agency.