Gedatolisib — Drug Monograph

Brand names: Revtorpyk

Drug class: PI3K Inhibitor

Mechanism of Action

Intravenous multi-target PI3K/AKT/mTOR (PAM) pathway inhibitor and the first FDA-approved agent that potently blocks all four Class I PI3K isoforms (alpha, beta, delta, gamma) together with both mTOR complexes (mTORC1 and mTORC2). This comprehensive vertical blockade of the PAM pathway suppresses a dominant driver of endocrine resistance in HR+/HER2- breast cancer and limits the feedback reactivation that constrains isoform-selective PI3K inhibitors. Unlike alpelisib, gedatolisib is active regardless of PIK3CA mutation status and is approved specifically for PIK3CA wild-type disease.

FDA Indications

• In combination with fulvestrant, with or without palbociclib, for HR-positive, HER2-negative, PIK3CA wild-type locally advanced or metastatic breast cancer in adults following progression on or after at least one line of endocrine therapy in the metastatic setting (FDA approved July 14, 2026; VIKTORIA-1: triplet median PFS 9.3 vs 2.0 months, HR 0.24; doublet 7.4 vs 2.0 months, HR 0.33)

Common Side Effects

• Stomatitis/mucositis
• Hyperglycemia
• Rash
• Fatigue
• Nausea
• Diarrhea
• Decreased appetite
• Neutropenia (in palbociclib triplet)

Clinical Pearl

Gedatolisib is the first PAM-pathway inhibitor approved for PIK3CA wild-type HR+/HER2- breast cancer - roughly 60% of this subtype - filling the gap left by alpelisib and capivasertib, which target PIK3CA/AKT-pathway-altered tumors. In VIKTORIA-1 the triplet (gedatolisib + palbociclib + fulvestrant) reduced the risk of progression or death by 76% versus fulvestrant. Start alcohol-free steroid mouthwash prophylactically - stomatitis is the signature toxicity of PAM inhibition (as with…

Related Therapies & Mechanisms

• Copanlisib (Aliqopa) — PI3K Inhibitor
• Duvelisib (Copiktra) — PI3K Inhibitor
• Inavolisib (Itovebi) — PI3K Inhibitor