NCCN Guidelines Add Gedatolisib-Based Regimens for Pretreated PIK3CA Wild-Type Advanced 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 for breast cancer as a preferred category 1 regimen for the second-line or subsequent-line treatment of patients with hormone receptor–positive, HER2-negative locally advanced or metastatic breast cancer without a PIK3CA mutation, following progression on or after at least 1 line of endocrine therapy.^1,2

This inclusion in the NCCN Guidelines follows the July 14, 2026, FDA approval of the gedatolisib-based regimens for this indication.³

“Because the NCCN Guidelines are a foundational resource for oncologists in determining the best course of treatment for patients, we believe these guidelines will increase awareness of [gedatolisib] and support informed treatment decision-making for patients with hormone receptor–positive/HER2-negative locally advanced or metastatic breast cancer,” Igor Gorbachevsky, MD, chief medical officer of Celcuity, stated in a news release.¹

Gedatolisib is expected to become commercially available in the US late in the third quarter of 2026, and eligible patients may enroll in the company’s expanded access program prior to commercial launch.

What data have supported the clinical integration of gedatolisib-based regimens into PIK3CA wild-type breast cancer clinical practice?

The FDA approval and NCCN Guidelines inclusion were based on findings from the PIK3CA wild-type cohort of the phase 3 VIKTORIA-1 trial (NCT05501886), an open-label, global, randomized study evaluating gedatolisib plus fulvestrant, with or without palbociclib, in patients with hormone receptor–positive, HER2-negative locally advanced or metastatic breast cancer following progression on or after CDK4/6 inhibitor therapy and an aromatase inhibitor.¹ In the trial, the gedatolisib triplet (gedatolisib plus palbociclib and fulvestrant; n = 131) produced a median progression-free survival (PFS) of 9.3 months (95% CI, 7.2-16.6) vs 2.0 months (95% CI, 1.8-2.3) with fulvestrant alone (n = 131), translating to an improvement of 7.3 months (HR, 0.24; 95% CI, 0.17-0.35; P < .0001).^1,3,4 The triplet elicited an objective response rate (ORR) of 31.5% (n = 124) vs 1.0% with fulvestrant alone (n = 105), and the median duration of response (DOR) was 17.5 months (95% CI, 8.8-not evaluable [NE]). The median DOR was not determinable for fulvestrant alone because only 1 objective response occurred in that arm.

The gedatolisib doublet (gedatolisib plus fulvestrant; n = 130) produced a median PFS of 7.4 months (95% CI, 5.5-9.9), translating to an improvement of 5.4 months vs fulvestrant alone (HR, 0.33; 95% CI, 0.24-0.48; P < .0001). The doublet elicited an ORR of 28.3% (n = 113), with a median DOR of 12.0 months (95% CI, 8.1-NE).

What are the safety considerations with gedatolisib?

The prescribing information for gedatolisib includes warnings and precautions for stomatitis, dermatologic adverse effects (AEs), hyperglycemia, and embryo-fetal toxicity. Stomatitis, which can be severe and include ulcers and oral mucositis, occurred at any grade in 72% of patients treated with the triplet (grade 3/4, 22%) and in 58% of patients treated with the doublet (grade 3/4, 12%).⁵ Rash occurred in 30% of patients receiving the triplet (grade 3/4, 6%) and in 40% of patients receiving the doublet (grade 3/4, 5%). Increased fasting glucose levels occurred in 46% of patients treated with the triplet (grade 3/4, 0.9%) and in 57% of patients treated with the doublet (grade 3/4, 1.8%). Notably, the safety profile of gedatolisib has not been established in patients with type 1 or uncontrolled type 2 diabetes.

Among patients treated with the triplet, the most common AEs, including laboratory abnormalities, occurring in at least 20% of patients were decreased white blood cell counts, decreased neutrophil counts, decreased hemoglobin levels, decreased lymphocyte counts, stomatitis, nausea, decreased platelet counts, increased fasting glucose levels, fatigue, vomiting, rash, constipation, diarrhea, increased alanine aminotransferase levels, increased aspartate aminotransferase levels, musculoskeletal pain, decreased sodium levels, and increased eosinophil levels.

References

1. Newly FDA-approved Revtorpyk (gedatolisib) included in the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines for HR+/HER2- locally advanced or metastatic breast cancer. News release. Celcuity Inc. July 30, 2026. Accessed August 3, 2026. https://ir.celcuity.com/news-releases/news-release-details/newly-fda-approved-revtorpyktm-gedatolisib-included-national
2. NCCN. Clinical Practice Guidelines in Oncology. Breast cancer, version 6.2026. July 29, 2026. Accessed August 3, 2026. https://www.nccn.org/professionals/physician_gls/pdf/breast.pdf
3. FDA approves gedatolisib with fulvestrant, with or without palbociclib, for HR-positive, HER2-negative locally advanced or metastatic breast cancer. FDA. July 14, 2026. Accessed August 3, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-gedatolisib-fulvestrant-or-without-palbociclib-hr-positive-her2-negative-locally
4. Hurvitz SA, Layman RM, Curigliano G, et al. Gedatolisib plus fulvestrant, with and without palbociclib, vs fulvestrant in patients with HR+/HER2-/PIK3CA wild-type advanced breast cancer: first results from VIKTORIA-1. Ann Oncol. 2025;36(suppl 2):S1562-S1563. doi:10.1016/j.annonc.2025.09.027
5. Revtorpyk. Prescribing information. Celcuity Inc; 2026. Accessed July 30, 2026. https://www.celcuity.com/wp-content/uploads/2026/04/REVTORPYK_PI_2026.pdf