FDA Approves Gedatolisib for HR+/HER2- Metastatic Breast Cancer

The Food and Drug Administration (FDA) has approved gedatolisib (Revtorpyk) for use in combination with fulvestrant, with or without palbociclib. This approval specifically targets adult patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative locally advanced or metastatic breast cancer.

Candidates for this treatment must not have a PIK3CA mutation and must have experienced disease progression following at least one line of endocrine therapy in the metastatic setting.

Clinical evidence: The VIKTORIA-1 trial

The regulatory decision was supported by results from Study 1 of VIKTORIA-1 (NCT05501886), an open-label, randomized, multicenter clinical trial. The study enrolled 392 adults with locally advanced or metastatic HR-positive, HER2-negative breast cancer. Participants were randomized in a 1:1:1 ratio to one of three treatment arms:

• Arm A: Gedatolisib in combination with fulvestrant and palbociclib.
• Arm B: Gedatolisib in combination with fulvestrant.
• Arm C: Fulvestrant monotherapy.

Treatment across all arms continued until the documentation of disease progression or the occurrence of unacceptable toxicity.

The primary efficacy outcome was progression-free survival (PFS) as assessed by a blinded independent central review. The trial demonstrated statistically significant improvements in PFS for both gedatolisib-containing regimens compared to fulvestrant alone.

In Arm A (the triplet combination), the median PFS was 9.3 months (95% CI: 7.2, 16.6), compared to 2.0 months (95% CI: 1.8, 2.3) in the control Arm C. This represented a hazard ratio (HR) of 0.24 (95% CI: 0.17, 0.35; p-value <0.0001).

In Arm B (the doublet combination), the median PFS reached 7.4 months (95% CI: 5.5, 9.9), again significantly outperforming the 2.0 months seen in Arm C. The hazard ratio for this comparison was 0.33 (95% CI: 0.24, 0.48; p-value <0.0001).

Secondary endpoints further supported the efficacy of the new treatment. The objective response rate (ORR) among patients with measurable disease was 32% in Arm A, 28% in Arm B, and 1% in Arm C. Additionally, the median duration of response (DoR) was 17.5 months in Arm A and 12.0 months in Arm B, while the DoR in the control arm was not estimable.

At the time of this analysis, overall survival (OS) data remained immature, with deaths occurring in 25% of the overall study population.

Safety profile and nursing considerations

For oncology nurses, managing the safety profile of gedatolisib is paramount. The prescribing information for the agent includes several critical warnings and precautions:

• Stomatitis: Patients should be monitored for oral inflammation and managed according to institutional protocols.
• Dermatologic adverse reactions: Skin toxicities may occur, requiring baseline and ongoing assessments.
• Hyperglycemia: Monitoring of blood glucose levels is necessary during treatment.
  Embryo-fetal toxicity: Patients of reproductive potential should be advised of the risks to a fetus.

Healthcare professionals are encouraged to report any serious adverse events to the FDA’s MedWatch Reporting System.

Dosage and administration

The recommended dosage for gedatolisib is 180 mg administered as an intravenous (IV) infusion over 30 minutes. The schedule follows a weekly administration on Days 1, 8, and 15 of every 28-day cycle. This regimen is maintained in combination with fulvestrant (with or without palbociclib) until the patient experiences disease progression or toxicity that is no longer manageable.

Streamlined regulatory review

The FDA utilized the Real-Time Oncology Review (RTOR) program for this application, which allows for the submission of data prior to the filing of the complete clinical application. The review also incorporated an Assessment Aid, a voluntary submission from the manufacturer intended to facilitate the FDA's evaluation process.

This approval provides a new therapeutic avenue for patients who have exhausted initial endocrine therapy options, offering a significant extension in progression-free survival through both doublet and triplet combination strategies.

Reference

1. U.S. Food and Drug Administration. FDA approves gedatolisib with fulvestrant, with or without palbociclib, for HR-positive, HER2-negative locally advanced or metastatic breast cancer. July 14, 2026. Accessed July 14, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-gedatolisib-fulvestrant-or-without-palbociclib-hr-positive-her2-negative-locally