Behind the Gedatolisib FDA Approval: An Investigator's Perspective on HR+ Breast Cancer

The FDA has approved gedatolisib (Revtorpyk), the first dual PI3K/mTOR pathway inhibitor, for patients with hormone receptor–positive, HER2-negative advanced breast cancer who lack a PIK3CA mutation—a group representing roughly 35% to 40% of this population that has had limited targeted treatment options after first-line CDK4/6 inhibitor therapy fails. The drug is approved in combination with fulvestrant, with or without palbociclib, based on results from the phase 3 VIKTORIA-1 trial, which showed significantly extended progression-free survival compared with fulvestrant alone.

Erica Stringer-Reasor, MD, of UAB's O'Neal Comprehensive Cancer Center, an investigator on trials supporting the approval, explained that gedatolisib works by simultaneously blocking the PI3K and mTOR pathways, targeting resistance mechanisms that limit single-pathway therapies. Practically, the drug is given intravenously on a weekly basis, with infusions lasting about 30 minutes—shorter than many other cancer therapies—and adverse effects that are generally manageable. The most common side effects observed in early trials were neutropenia, stomatitis, and rash, all conditions oncologists are already experienced in managing, and Stringer-Reasor emphasized the value of proactive prophylactic strategies.

Looking ahead, she anticipates further combination regimens, including potential use of oral selective estrogen receptor degraders in place of intravenous fulvestrant. She also stressed the importance of investigating resistance mechanisms more broadly and exploring dual- or triple-pathway blockade strategies, rather than focusing solely on biomarker-driven approaches, to help close treatment gaps for patients without actionable mutations like ESR1 or PIK3CA.

Reflecting on her role in the drug's development, Stringer-Reasor described the meaningful bonds formed between patients and nursing staff during IV treatment visits, and highlighted improved quality of life for patients now able to travel and spend time with family while on therapy with fewer adverse effects.

Read the full interview with Dr Stringer-Reasor.