ESMO 2025 Gedatolisib in combination with palbociclib and fulvestrant improves progression-free survival in HR+, HER2- advanced breast cancer with progression

MedNet.nl: In patients with hormone receptor-positive, HER2-negative breast cancer that progresses after treatment with a CDK4/6 inhibitor and an aromatase inhibitor, combination therapy with the multitarget inhibitor gedatolisib plus palbociclib and fulvestrant leads to improved progression-free survival (PFS) compared with fulvestrant alone. This is shown by the phase 3 VIKTORIA-1 study.

Gedatolisib is a multitarget inhibitor that acts on PI3K, AKT, and mTOR, also known as the PAM pathway. The researchers of the VIKTORIA-1 study investigated the effect of gedatolisib with palbociclib and fulvestrant in patients who showed progression after treatment with a CDK4/6 inhibitor and an aromatase inhibitor.

The patients were tested for PIK3CA mutations prior to the study. Patients with and without these mutations were treated in separate parts of the study. During ESMO, the researchers presented data on the study in patients with wild-type PIK3CA. In this part, 392 patients were randomized to three treatment arms: gedatolisib plus palbociclib plus fulvestrant (arm A), gedatolisib plus fulvestrant (arm B), or fulvestrant alone (arm C). Patients with progression could switch to arm A or arm B.

After a median follow-up of 10.1 months, the median PFS in arms A and B was 9.3 months and 7.4 months, respectively, versus 2.0 months in the fulvestrant arm. This resulted in hazard ratios (HR) of 0.24 and 0.33, respectively. Data on overall survival (OS) showed a trend toward better survival in the gedatolisib groups. In arms A and B, the median OS was 23.7 months and "not yet reached" versus 18.5 months in the fulvestrant arm (HRs=0.69 and 0.74, respectively). The objective response rates (ORR) were also higher: 32.0% and 28.3% versus 1.0%.

The treatments were relatively well tolerated. A respective 2.3%, 3.1%, and 0.0% discontinued treatment due to side effects.

The results show that the PAM pathway is a target for treatment in PIK3CA wild-type breast cancer, the researchers say.

Hurvitz SA, et al. Gedatolisib (geda) + fulvestrant ± palbociclib (palbo) vs fulvestrant in patients (pts) with HR+/ HER2-/PIK3CA wild-type (WT) advanced breast cancer (ABC): first results from VIKTORIA-1. ESMO 2025, abstract LBA17.

This article was originally published in Dutch on MedNet.nl