On July 14, the U.S. Food and Drug Administration (FDA) approved gedatolisib (Revtorpyk) in combination with fulvestrant, with or without palbociclib, for the treatment of adults with hormone receptor (HR)-positive, HER2-negative locally advanced or metastatic breast cancer without a PIK3CA mutation detected following disease progression on or after treatment with at least one line of endocrine therapy in the metastatic setting.
VIKTORIA-1
Efficacy was evaluated in Study 1 of VIKTORIA-1 (ClinicalTrials.gov identifier NCT05501886), an open-label, randomized, multicenter trial that enrolled 392 adults with locally advanced (inoperable) or metastatic HR-positive, HER2-negative breast cancer. Patients were randomly assigned 1:1:1 to receive either gedatolisib in combination with fulvestrant and palbociclib (Arm A), gedatolisib in combination with fulvestrant (Arm B), or fulvestrant alone (Arm C). Patients received treatment until disease progression or unacceptable toxicity.
The major efficacy outcome measure was comparison of progression-free survival, assessed by blinded independent central review between patients enrolled in Arm A and Arm C, and between patients enrolled in Arm B and Arm C, evaluated according to Response Evaluation Criteria in Solid Tumors version 1.1. Additional efficacy outcome measures were overall survival, objective response rate, and duration of response.
There was a statistically significant improvement in progression-free survival for Arm A vs Arm C, with a median progression-free survival of 9.3 months (95% confidence interval [CI] = 7.2–16.6 months) in Arm A and 2.0 months (95% CI = 1.8–2.3 months) in Arm C (hazard ratio [HR] = 0.24; 95% CI = 0.17–0.35; P < .0001). There was also a statistically significant improvement in progression-free survival seen for Arm B vs Arm C, with a median progression-free survival of 7.4 months (95% CI = 5.5–9.9 months) in Arm B and 2.0 months (95% CI = 1.8–2.3 months) in Arm C (HR = 0.33; 95% CI = 0.24–0.48; P < .0001).
The objective response rate in patients with measurable disease was 32% (95% CI = 23%–40%) in Arm A, 28% (95% CI = 20%–38%) in Arm B, and 1% (95% CI = 0%–5%) in Arm C. The median duration of response was 17.5 months (95% CI = 8.8 months to not estimable) in Arm A, 12.0 months (95% CI = 8.1 months to not estimable) in Arm B, and not estimable in Arm C.
At the time of the progression-free survival analysis, overall survival data were not mature with 25% deaths in the overall population.
The prescribing information includes warnings and precautions for stomatitis, dermatologic adverse reactions, hyperglycemia, and embryo-fetal toxicity.
Recommended Dosage
The recommended dosage for gedatolisib is 180 mg as an intravenous infusion over 30 minutes once weekly on days 1, 8, and 15 of every 28-day cycle, in combination with fulvestrant, with or without palbociclib, until disease progression or unacceptable toxicity. Refer to the prescribing information for fulvestrant and palbociclib for additional dosing information.
This review used the Real-Time Oncology Review program, which streamlined data submission prior to the filing of the entire clinical application, and the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment.
