5 days ago
Pfizer and Arvinas gamble to shift breast cancer treatment paradigm
Breast cancer (BC) is the most prevalent cancer among women globally with two million diagnosed cases each year. Oestrogen receptor (ER) is expressed in most invasive BC cases (70 to 80%). Many therapies have therefore been developed to target this receptor, including fulvestrant, and more recently the CDK4/6 inhibitors, which act synergistically with endocrine therapies. But following exposure to endocrine and CDK4/6 inhibitor therapy, many patients quickly acquire ER mutations (ESR1m), leading to treatment resistance and leaving a significant unmet need.
Pfizer's and Arvinas' vepdegestrant is an oral proteolysis-targeting chimera (PROTAC) ER degrader. The drug exploits the ubiquitin-proteasome system, degrading the mutant ER complex and greatly slowing growth and increasing tumour survivability. As the drug drives degradation and more specific targeting than small-molecule ER inhibitor receptors in preclinical studies, this class could leave a more profound effect with a tolerable safety profile. In the Phase II VERITAC trial, the drug was well-tolerated in a heavily CDK4/6 inhibitor pre-treated BC patient setting. Of 35 patients receiving 200mg of vepdegestrant, there was only one discontinuation and no dose reductions.
A press release by Arvinas announced the results from the Phase III trial, VERITAC-2. Significant improvements to progression-free survival were seen with a hazard ratio of 0.60 in the ESR1m patient subpopulation for patients receiving vepdegestrant monotherapy compared to fulvestrant. This improvement was not seen in the overall population, including non-ESR1m patients. These patients had previously experienced progression following CDK4/6 inhibitor treatment. The full trial results are to be announced on 31 May at the 2025 American Society of Clinical Oncology conference.
While initial safety and efficacy results are positive, the recent controversy surrounding the efficacy of CDK4/6 inhibitors in improving overall survival for breast cancer patients will hurt sales and the growth of the market share accessible to vepdegestrant. Regardless, the projected impact of vepdegestrant is suspected to be strong for the ESR1m population, which currently affects up to 39% of endocrine-resistant metastatic BC cases. GlobalData's analyst consensus forecasts estimate the drug to reach $1.64 billion in sales for metastatic breast cancer by 2031.
"Pfizer and Arvinas gamble to shift breast cancer treatment paradigm" was originally created and published by Clinical Trials Arena, a GlobalData owned brand.
The information on this site has been included in good faith for general informational purposes only. It is not intended to amount to advice on which you should rely, and we give no representation, warranty or guarantee, whether express or implied as to its accuracy or completeness. You must obtain professional or specialist advice before taking, or refraining from, any action on the basis of the content on our site.
