Serious adverse events occurred in 32% of patients in the fulvestrant/taselisib group, compared with 8.9% of controls. Grade 3 or greater side effects occurred in 49.5% vs. 16.4%, respectively, and side effects leading to discontinuation of taselisib occurred in 16.8% of patients, vs. 2.3% of those on placebo.
The primary toxicities were gastrointestinal effects, especially diarrhea, which occurred in 60.1% vs. 19.7% of patients (all grades). Hyperglycemia occurred in 40.4% of patients on taselisib, vs. 9.4% on placebo.
Dr. Baselga noted that the secondary endpoints of overall response rate, clinical benefit rate, and duration of response all favored taselisib.
Asked whether taselisib was the right agent in this setting, given the commercial availability of at least two other PI3K inhibitors – idelalisib (Zydelig) and copanlisib (Aliqopa) – Dr. Baselga agreed that another, more specific agent may offer similar or better efficacy with fewer off-target effects. He noted that taselisib is highly active against the alpha isoforms of PI3K, but also hits the delta and gamma isoforms.
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Dr. Cynthia X Ma
“The side effects that we see that are limiting patients staying on [taselisib] are mostly delta and gamma. So I do think that in the case of breast cancer, what we need to do is to work on more specific alpha inhibitors that will be safer,” he said.