medwireNews: Patients with hormone receptor (HR)-positive, HER2-negative metastatic breast cancer harboring PI3KCA mutations derive a significant progression-free survival (PFS) benefit when fulvestrant is supplemented with the PI3K inhibitor alpelisib, phase III data show.
Presenting the results at the ESMO 2018 Congress in Munich, Germany, Fabrice André (Institut Gustave Roussy, Villejuif, France) explained that alpelisib is a highly specific PI3K inhibitor, targeting just the alpha isoform of the protein, unlike other drugs in this class that target all four isoforms and are therefore associated with high levels of toxicity.
The double-blind SOLAR-1 trial comprised two cohorts– one with activating PI3KCA mutations and one without (n=341 and 231, respectively) – of men and postmenopausal women who had received aromatase inhibitor therapy for advanced breast cancer.
Over a median follow-up of 20.0 months, treatment with oral alpelisib 300 mg/day plus fulvestrant was associated with a significant 35% reduction in the risk for disease progression or death relative to placebo and fulvestrant in the PI3KCA-mutant cohort.
The median PFS duration was nearly doubled in the alpelisib plus fulvestrant group, at 11.0 months compared with 5.7 months for the placebo and fulvestrant group.
Alpelisib treatment was also associated with a significantly higher overall response rate in this cohort, at 26.6% versus 12.8% with placebo. The corresponding rates were 35.7% and 16.2% in the subgroup of 262 patients with measurable disease, also a significant difference.
By contrast, there was “no clinically relevant effect” of adding alpelisib in patients with tumors lacking PI3KCA mutations, which provides the proof of concept for PI3KCA mutations as a biomarker for alpelisib therapy, said André.
With regard to the safety profile, adverse events (AEs) of grade 3 or 4 occurred in 76% of all patients given alpelisib plus fulvestrant and in 36% of those who received placebo, but led to treatment discontinuation in just 5% and 1% of patients, respectively.
Among alpelisib-treated participants, the most common AE at these grades was hyperglycemia (36.6 vs 0.6% for placebo), followed by rash (9.9 vs 0.3%).
“Alpelisib offers the potential for increased life expectancy in patients with HR+ HER2- advanced breast cancer with PI3KCA mutations,” André said in a press release, noting, however, that the short follow-up does not allow conclusions to be drawn about the long-term survival benefit of the drug.
medwireNews is an independent medical news service provided by Springer Healthcare. © 2018 Springer Healthcare part of the Springer Nature group