FDA Approves Gedatolisib for HR+, HER2– PIK3CA Wild-Type Advanced Breast Cancer

The FDA has approved gedatolisib (Revtorpyk) in combination with fulvestrant with or without palbociclib (Ibrance) for patients with hormone receptor (HR)–positive, HER2-negative (HER2–), PIK3CA wild-type advanced breast cancer following disease progression on or after at least 1 line of endocrine therapy.¹

“In my opinion, I think this could be immediately practice changing. The progression-free survival 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^®.

The recommended dosage of gedatolisib was 180 mg intravenously for 30 minutes once weekly on days 1, 8, and 15, of every 28 day cycle.

The approval was based on results from the phase 3 VIKTORIA-1 trial (NCT05501886), which were presented at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting. The study enrolled 362 patients in a 3:3:1 randomization to the gedatolisib , palbociclib (Ibrance), or fulvestrant (Arm D; n = 155), alpelisib (Vijoice) plus fulvestrant (Arm E; n = 155), or gedatolisib plus fulvestrant (Arm F; n = 52), following progression on a CDK4/6i and non-steroidal aromatase inhibitor. The data cutoff was March 9, 2026, with a median follow-up of 12.8 months.

The primary end point of progression-free survival (PFS) by blinded independent central review (BICR) in the PIK3CA-mutant population, the gedatolisib triplet achieved a median PFS of 11.1 months (95% CI, 9.0-16.7) compared with 5.6 months (95% CI, 5.2-7.4) for alpelisib plus fulvestrant, representing a 50% reduction in the risk of disease progression or death (HR, 0.50; 95% CI, 0.37-0.68; P <.0001). The gedatolisib doublet similarly improved PFS, with a median of 11.3 months (95% CI, 9.1-22.1) vs 5.6 months (95% CI, 5.2-7.4) for alpelisib plus fulvestrant (HR, 0.51; 95% CI, 0.33-0.79; P = .0013). PFS benefit for the triplet was consistent across all prespecified subgroups, including by age, menopausal status, presence of visceral metastasis, prior CDK4/6i received, and time to progression on the immediate prior therapy.

At the interim analysis, overall survival (OS), which is a key secondary end point, had a median OS had not been reached for the gedatolisib triplet vs 31.1 months (95% CI, 20.0-not estimable [NE]) for alpelisib plus fulvestrant (HR, 0.76; 95% CI, 0.50-1.14; P = .0908), with OS data not yet mature (45.8% of required events reached). In the gedatolisib plus fulvestrant arm, the median OS was 22.8 months (95% CI, 17.6-NE) vs 31.1 months (95% CI, 20.0-NE) in the alpelisib arm (HR, 0.93; 95% CI, 0.55-1.60; P = .4026).

In the triplet arm, the objective response rate (ORR) was 48.9% with a median duration of response (DOR) of 15.7 months (95% CI, 9.2-20.6). In the doublet arm, the ORR was 35.7% with a median DOR of 24.2 months (95% CI, 7.4- NE). Additionally, there was the 26.0% ORR and 7.5-month median DOR (95% CI, 5.5-15.8) observed in the alpelisib plus fulvestrant arm. The clinical benefit rate was 69.9% in the triplet arm, 73.8% in the doublet arm, and 45.7% in the alpelisib plus fulvestrant arm.

Hyperglycemia occurred in 57.9% of patients in the alpelisib plus fulvestrant arm at any grade, compared with only 15.0% in the gedatolisib triplet arm and 11.5% in the doublet arm. Diarrhea occurred in 40.1% of patients in the alpelisib arm vs 15.0% and 9.6% in the triplet and doublet arms, respectively.

Treatment-related study discontinuation due to adverse events was low across gedatolisib arms, with 2.6% for the triplet and 3.8% for the doublet arm compared with 7.1% for alpelisib plus fulvestrant. The most common treatment-related adverse events for gedatolisib-based regimens included neutropenia (63.4% for the triplet; 1.9% for the doublet), stomatitis (61.4% vs 61.5% for the doublet), and nausea (45.8% vs 40.4%). Treatment-related serious adverse events occurred in 10.5% and 3.8% of triplet and doublet patients, respectively, vs 13.2% in the alpelisib arm.

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. https://tinyurl.com/yck3eabf
2. Hurvitz SA et al. A randomized, open-label, phase 3 study of gedatolisib + fulvestrant ± palbociclib vs standard of care in HR+/HER2−/PIK3CA-mutant (MT) advanced breast cancer (VIKTORIA-1 Study 2). J Clin Oncol. 44, 2026 (suppl 17; abstr LBA1008). doi:10.1200/JCO.2026.44.17_suppl.LBA1008