NCCN Lists Gedatolisib Regimens as Preferred Option in HR+/HER2– Metastatic Breast Cancer

Gedatolisib (Revtorpyk), in combination with fulvestrant (Faslodex), with or without palbociclib (Ibrance), has been added to the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology as a preferred Category 1 regimen for second-line and subsequent treatment of hormone receptor–positive (HR+), HER2-negative, locally advanced or metastatic breast cancer without a PIK3CA mutation. The listing applies to patients whose disease has progressed on or after at least 1 line of endocrine therapy in the metastatic setting.¹

The guideline update follows FDA approval of gedatolisib on July 14, 2026, for the same PIK3CA wild-type population. Gedatolisib is the first agent approved to inhibit all 4 class I PI3K isoforms (α, β, δ, γ) together with mTOR complexes 1 and 2, producing downstream inhibition of AKT and other pathway effectors.

The approval and subsequent guideline inclusion are based on the PIK3CA wild-type cohort of the phase 3 VIKTORIA-1 trial (NCT05501886), an open-label, global, randomized study of gedatolisib plus fulvestrant, with or without palbociclib, in patients with HR+/HER2-negative locally advanced or metastatic breast cancer who had progressed after treatment with a CDK4/6 inhibitor and an aromatase inhibitor.²

In the triplet arm (gedatolisib, palbociclib, and fulvestrant), median progression-free survival (PFS) was 9.3 months vs 2.0 months with fulvestrant alone, a difference of 7.3 months (HR, 0.24; 95% CI, 0.17-0.35; P <.0001).¹ The objective response rate (ORR) was 32% with the triplet vs 1% with fulvestrant, and median duration of response (DOR) was 17.5 months. In the doublet arm (gedatolisib plus fulvestrant), median PFS was 7.4 months vs 2.0 months with fulvestrant (HR, 0.33; 95% CI, 0.24-0.48; P <.0001), with an ORR of 28% and a median DOR of 12.0 months; DOR was not evaluable in the fulvestrant arm because only 1 response occurred.

"The inclusion of [gedatolisib] in the NCCN Guidelines shortly after FDA approval highlights the clinical relevance of this treatment option," Igor Gorbachevsky, MD, chief medical officer of Celcuity, said in a statement, adding that the listing is expected to increase awareness of the regimen among oncologists making treatment decisions for this patient population.¹

Safety monitoring for gedatolisib centers on 3 principal toxicities outlined in the prescribing information. Stomatitis occurred in 72% of patients receiving the triplet (22% grade 3) and 58% of those receiving the doublet (12% grade 3); a steroid-containing, alcohol-free mouthwash is recommended prophylactically before and during treatment. Rash occurred in 30% of patients on the triplet (6% grade 3) and 40% of those on the doublet (5% grade 3), with guidance to limit sun exposure during treatment. Hyperglycemia occurred in 46% of patients on the triplet (grade 3, 0.9%) and 57% of those on the doublet (grade 3, 1.8%); fasting glucose should be assessed before and periodically during treatment, and the drug's safety has not been established in patients with type 1 or uncontrolled type 2 diabetes. Gedatolisib also carries an embryo-fetal toxicity warning, and effective contraception is advised during treatment and for 2 weeks after the final dose for patients and partners of reproductive potential. Dose modification or discontinuation may be required based on the severity of any of these events.

Additional adverse reactions occurring in 20% or more of patients across the 2 combinations included cytopenias, nausea, fatigue, vomiting, constipation, diarrhea, elevated transaminases, musculoskeletal pain, and electrolyte abnormalities.

Gedatolisib is expected to become commercially available in the United States in the third quarter of 2026. Before commercial launch, eligible patients may be able to access the agent through Celcuity's expanded access program, with physician enrollment requests directed to the company.

Gedatolisib is also under investigation for first-line treatment of HR+/HER2-negative advanced breast cancer in the phase 3 VIKTORIA-2 trial (NCT06757634) and for second-line treatment of metastatic castration-resistant prostate cancer in combination with darolutamide in the phase 1/2 CELC-G-201 trial.¹

REFERENCES

1. Newly FDA-approved REVTORPYK (gedatolisib) included in the National Comprehensive Cancer Network Clinical Practice Guidelines for HR+/HER2- locally advanced or metastatic breast cancer. News release. Celcuity Inc. July 30, 2026. Accessed July 31, 2026. https://tinyurl.com/3sbmv78s

2. Hurvitz SA, Layman RM, Curigliano G, et al. VIKTORIA-1 trial of gedatolisib plus fulvestrant with or without palbociclib in hormone receptor–positive/HER2−/PIK3CA wild-type advanced breast cancer. J Clin Oncol. Published online March 9, 2026. doi:10.1200/JCO-25-02643