Gedatolisib Combination Approved for PIK3CA Wild-Type HR+, HER2– Breast Cancer

The FDA approved gedatolisib (Revtorpyk; Celcuity Inc) in combination with fulvestrant (Faslodex; AstraZeneca), with or without palbociclib (Ibrance; Pfizer), for adults with hormone receptor–positive (HR+), HER2-negative (HER2–) locally advanced or metastatic breast cancer without a PIK3CA mutation, following progression on or after at least 1 line of endocrine therapy in the metastatic setting. The approval follows priority review, which was granted in January 2026.¹

The FDA approval of gedatolisib represents one of the most significant advances this year for patients with HR+, HER2– advanced breast cancer, introducing the first approved multitarget PI3K/AKT/mTOR inhibitor. Unlike earlier agents that inhibit only a single component of the PI3K pathway, gedatolisib blocks all 4 class I PI3K isoforms along with mTORC1/2.

This broader pathway inhibition is designed to address adaptive signaling that can contribute to endocrine resistance, offering a novel mechanism of action for patients whose disease has progressed despite prior endocrine therapy.²

Clinical Trial Data Supporting the Approval: The Phase 3 VIKTORIA-1 Trial

The approval is based on results from Study 1 of the phase 3 VIKTORIA-1 trial (NCT05501886)³, an open-label, randomized, multicenter study that enrolled 392 adults with locally advanced or metastatic HR+, HER2– breast cancer. Patients were randomly assigned 1:1:1 to gedatolisib plus fulvestrant and palbociclib (triple regimen; arm A), gedatolisib plus fulvestrant (doublet regimen; arm B), or fulvestrant alone (arm C), continuing treatment until disease progression or unacceptable toxicity.^1,3

The major efficacy outcome was progression-free survival (PFS), assessed by blinded independent central review, comparing arms A and C as well as arms B and C.³

In the PIK3CA wild-type population, the triplet regimen produced a median PFS of about 9.3 months compared with 2.0 months for fulvestrant alone, an approximate 76% reduction in the risk of progression or death (HR, 0.24 [95% CI, 0.17-0.35]; P < .0001). Additionally, the doublet regimen achieved a median PFS of 7.4 months compared with 2.0 months for the fulvestrant alone arm (67% risk reduction; HR, 0.33 [95% CI, 0.24-0.48]; P < .0001).^1-3

Objective response rates among patients with measurable disease were approximately 32% in the triplet arm and 28% in the doublet arm, compared with just 1% with fulvestrant monotherapy. Further, the median duration of response was 17.5 months with the triplet and 12.0 months with the doublet, and the value for the control arm was not estimable.

Overall survival data were not yet mature at the time of the PFS analysis, with 25% of patients in the overall population having died.¹ Regardless, the regimen maintains a magnitude of benefit, potentially setting a new benchmark for the post-CDK4/6 inhibitor, PIK3CA wild-type setting, which is an area that previously lacked practice-changing phase 3 evidence.³

Safety and Dosing

The prescribing information carries warnings and precautions for stomatitis, dermatologic adverse reactions, hyperglycemia, and embryo-fetal toxicity.¹ Neutropenia and stomatitis were among the most common adverse events (AEs) reported, consistent with the known effects of PAM pathway blockade combined with CDK4/6 inhibition.³

The recommended dosage of gedatolisib is 180 mg administered as a 30-minute IV infusion once weekly on days 1, 8, and 15 of each 28-day cycle, given alongside fulvestrant with or without palbociclib. The FDA recommends that health care professionals consult the individual prescribing information for those agents for additional dosing guidance.¹

What Gedatolisib’s Approval Means for Pharmacists, Patients

The approval is particularly important because it expands targeted treatment options for patients who have PIK3CA wild-type disease, an area where few effective therapies have been available. Existing PI3K inhibitors are limited to patients with PIK3CA-mutated tumors, leaving many patients with wild-type disease to receive fulvestrant alone or transition to chemotherapy after progression on CDK4/6 inhibitors.

For oncology pharmacists, the approval also introduces new considerations for treatment selection and patient management. Gedatolisib is approved both in combination with fulvestrant alone and with fulvestrant plus palbociclib, giving pharmacists and other clinicians flexibility based on a patient's prior CDK4/6 inhibitor exposure, tolerability, and treatment history. The inclusion of a triplet regimen that reintroduces a CDK4/6 inhibitor after prior progression is a notable aspect of the approval and may prompt discussions about optimal sequencing, toxicity management, and patient counseling as the agent is incorporated into clinical practice.

REFERENCES

1. FDA approves gedatolisib with fulvestrant, with or without palbociclib, for HR-positive, HER2-negative locally advanced or metastatic breast cancer. News release. FDA. 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

2. Gedatolisib Plus Fulvestrant With or Without Palbociclib vs Standard-of-Care for the Treatment of Patients With Advanced or Metastatic HR+/​HER2- Breast Cancer (VIKTORIA-1) (VIKTORIA-1). ClinicalTrials.gov identifier: NCT05501886. Updated February 10, 2026. Accessed July 14, 2026. https://clinicaltrials.gov/study/NCT05501886

3. Valletti D. FDA Grants Priority Review to Gedatolisib for HR+, HER2-Negative Advanced Breast Cancer. Pharmacy Times. January 21, 2026. Accessed July 14, 2026. http://pharmacytimes.com/view/fda-grants-priority-review-to-gedatolisib-for-hr-her2-negative-advanced-breast-cancer