For patients with the most common form of advanced breast cancer, one class of targeted drugs has come with a catch: it only works if the tumor carries a specific mutation, called PIK3CA, which roughly 40 percent of patients have. The other 60 percent have had no PI3K-pathway option at all. On July 14, the FDA approved a drug that changes that [1].
The drug, gedatolisib - brand name Revtorpyk - is the first approved to block the entire PI3K/mTOR pathway, and it works regardless of PIK3CA mutation status [1][2]. In its Phase 3 trial, combined with standard therapy, it extended median progression-free survival - the time before the cancer worsens - to 9.3 months for the three-drug regimen and 7.4 months for the two-drug version, against about 2 months for the older standard alone [1].
Data
| Fulvestrant alone | 2 median progression-free survival (months) |
|---|---|
| Gedatolisib doublet | 7.4 median progression-free survival (months) |
| Gedatolisib triplet | 9.3 median progression-free survival (months) |
The second improvement is tolerability. The older PI3K inhibitor, alpelisib, is notorious for side effects that push patients off it - severe diarrhea in roughly 40 percent, high blood sugar in more than half [1]. Gedatolisib's trial reported those at a fraction of the rate: severe diarrhea in about 1.5 percent, high blood sugar in about 2 percent [1]. A drug patients can actually stay on is part of what makes the survival number meaningful.
Two caveats belong with the good news. The approval extends the time before progression, a real and important endpoint, though longer-term overall-survival data will take more time to mature [1]. The pivotal trial was also run by the drug's maker, as most are, with the FDA's clearance as the independent check [2]. For a large group of patients who had no targeted option, a drug that multiplies the time before their cancer advances, with far less of the toxicity that ended older treatments, is a genuine step [1].
