Gedatolisib/Fulvestrant Earns NCCN Category 1 Listing for HR+/HER2- Breast Cancer

Gedatolisib (Revtorpyk), the first agent to inhibit all class I PI3K isoforms alongside both mTOR complexes, 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 option for patients with hormone receptor (HR)–positive, HER2-negative, locally advanced or metastatic breast cancer, according to a press release from Celcuity Inc.¹

The NCCN listing arrives just over 2 weeks after the FDA approved gedatolisib in combination with fulvestrant, with or without palbociclib, for patients whose tumors lack a PIK3CA mutation and who have progressed on at least 1 line of endocrine therapy in the metastatic setting.²

“The inclusion of [gedatolisib] in the NCCN Guidelines shortly after FDA approval highlights the clinical relevance of this treatment option for patients with advanced breast cancer,” said Igor Gorbachevsky, chief medical officer of Celcuity.¹ “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 [HR-positive/HER2-negative] locally advanced or metastatic breast cancer.”

Supporting data for the approval comes from the phase 3 VIKTORIA-1 trial (NCT05501886), an open-label, global, randomized study that compared gedatolisib combinations with fulvestrant alone in patients whose disease had progressed after a CDK4/6 inhibitor plus an aromatase inhibitor.³ Patients assigned to the gedatolisib triplet, consisting of gedatolisib, palbociclib, and fulvestrant, had a median progression-free survival (PFS) of 9.3 months, compared with 2.0 months for fulvestrant alone (HR, 0.24; 95% CI, 0.17-0.35; P <.0001). The objective response rate (ORR) was 31.5% with the triplet vs 1.0% with fulvestrant, and the median duration of response (DOR) was 17.5 months. The doublet, consisting of gedatolisib plus fulvestrant, produced a median PFS of 7.4 months against the same 2.0-month comparator arm (HR, 0.33; 95% CI, 0.24-0.48; P <.0001), with a 28.3% ORR and a 12.0-month median DOR.

“In my opinion, I think this could be immediately practice-changing. The [PFS] data that we're seeing in both the PIK3CA wild-type and PIK3CA-mutant populations was consistently better than in the control arm. This is really meaningful for patients,” Sara Hurvitz, MD, FACP, physician, senior vice president and director of Clinical Research Division, professor of Clinical Research Division, and Smith Family Endowed Chair in Women’s Health at Fred Hutch, said during an interview with CancerNetwork at the time of the approval^®.

Gedatolisib’s safety profile included stomatitis, including ulcers and oral mucositis, which occurred in 72% of patients who received the triplet regimen and 58% of those on the doublet. The prescribing information calls for starting a steroid-containing, alcohol-free mouthwash before treatment begins and continuing prophylactically throughout therapy. Rash was reported in 30% of patients who were given the triplet and 40% of patients who were given the doublet, with guidance to limit sun exposure during treatment. Hyperglycemia is another labeled risk, with increased fasting glucose reported in 46% of triplet patients and 57% of doublet patients. Notably, the safety of gedatolisib has not been studied in patients with type 1 or uncontrolled type 2 diabetes, and clinicians are advised to check fasting glucose and HbA1c levels before and periodically during treatment. Gedatolisib also carries an embryo-fetal toxicity warning, requiring effective contraception during treatment and for 2 weeks after the final dose for patients and partners of reproductive potential. Patients are advised not to breastfeed during that same window.

Gedatolisib is also being evaluated in additional settings. The ongoing phase 2 VIKTORIA-2 trial (NCT06757634) is testing gedatolisib combinations as first-line therapy in treatment-naive patients with advanced HR-positive, HER2-negative breast cancer, across both endocrine-resistant and endocrine-sensitive cohorts. A separate early-phase trial is examining gedatolisib alongside darolutamide in metastatic castration-resistant prostate cancer.

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. July 30, 2026. Accessed July 31, 2026. https://tinyurl.com/2ma4knfw
2. 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 31, 2026. https://tinyurl.com/yck3eabf
3. Hurvitz SA, Layman RM, Curigliano G, et al. Gedatolisib Plus Fulvestrant, With & Without Palbociclib, vs Fulvestrant in Patients With HR+/HER2-/PIK3CA Wild-Type Advanced Breast Cancer: First Results from VIKTORIA-1. Presented at: 2025 ESMO Annual Congress; October 17-21, 2025; Berlin, Germany. Abstract LBA17.