HQ Team
June 1, 2025: An investigational oral breast cancer drug being developed by Pfizer and Arvinas Inc. has been shown to delay progression of the disease by three months compared to AstraZeneca’s Faslodex or fulvestrant.
The end-stage trial was evaluating vepdegestrant monotherapy versus fulvestrant in adult patients with a specific gene mutation.
Vepdegestrant demonstrated a “statistically significant and clinically meaningful improvement in progression-free survival (PFS) among patients with an estrogen receptor 1 (ESR1) mutation, reducing the risk of disease progression or death by 43% compared to fulvestrant,” according to a joint statement.
“The median PFS, as assessed by blinded independent central review, was five months with vepdegestrant versus 2.1 months with fulvestrant.”
Intent-to-Treat
The trial “did not reach statistical significance” in improvement in disease progression in the intent-to-treat population, with a median PFS of 3.7 months for vepdegestrant compared to 3.6 for fulvestrant.
Intent-to-Treat is a concept primarily used in clinical trials to include all randomised patients in the analysis, regardless of whether they completed the study or deviated from the protocol.
It is considered a more conservative approach to evaluating treatment effects because it accounts for real-world scenarios where patients may not adhere to the treatment plan perfectly.
Vepdegestrant belongs to the PROTAC ER degraders class of drugs, which are developed to harness the body’s natural protein disposal system to target and degrade proteins that aid tumour growth.
Global pact
In July 2021, Arvinas announced a global collaboration with Pfizer for the co-development and co-commercialisation of vepdegestrant. Arvinas and Pfizer will share worldwide development costs, commercialisation expenses, and profits.
The trial results “are promising and suggest that vepdegestrant could offer a much-needed treatment option for these patients, with a low incidence of burdensome GI effects that can meaningfully affect daily life,” said Erika P. Hamilton, M.D., Director, Breast Cancer Research, Sarah Cannon Research Institute, and a principal investigator of the trial.
“Patients whose tumours harbour ESR1 mutations can face a poor prognosis, often experiencing rapid disease progression on endocrine therapy,” said Johanna Bendell, M.D., Chief Oncology Development Officer, Pfizer. “These results highlight the important role vepdegestrant may play in combating ESR1 mutation treatment resistance for these patients.”
About 2.3 million new breast cancer diagnoses were reported globally in 2022, and it is estimated that there will be nearly 320,000 new diagnoses in the United States in 2025. ER+/HER2- breast cancer accounts for approximately 70% of all cases.
Breast cancer is the second most common cancer and one of the leading causes of cancer-related deaths worldwide. More than two million patients were diagnosed with breast cancer in 2022, with more than 665,000 deaths globally.
