Next-gen oral breast cancer drugs near commercialization

AZ and Pfizer in fierce competition

Estrogen receptor degrader (SERD) research results unveiled at ASCO 2025

Second oral SERD drug challenge after Menarini... Both companies show effect in Phase III trials

The arrival of next-generation oral selective estrogen receptor degraders (SERDs) is imminent.

 

At the American Society of Clinical Oncology (ASCO) Annual Meeting 2025 which was held in Chicago, USA, from the 30th of last month to the 4th, multinational pharmaceutical companies simultaneously disclosed the results of their Phase III clinical trials for their oral SERD candidates.

 

At this conference, Pfizer's vepdegestrant and AstraZeneca's camizestrant both presented positive research results.

 

SERDs are primarily used as a treatment option for patients with breast cancer who are resistant to endocrine therapy.

 

Until now, AstraZeneca's Faslodex, an injectable drug, had been the main option.

 

Following this, Menarini's 'Orserdu' emerged as the first oral SERD option, and Lilly completed clinical trials for ‘Inluriyo ‘and submitted an application for its regulatory approval.

 

If latecomers Pfizer and AstraZeneca both succeed in commercializing their products, it is expected that the SERD market will see greater utilization of oral treatment options.

 

#Oral SERD using PROTAC technology… green light lit to its commercialization AstraZeneca announced at the conference that the combination therapy of camizestrant and CDK4/6 inhibitors demonstrated statistically significant improvements in progression-free survival (PFS).

 

Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors are treatment options for patients with hormone receptor (HR)-positive, HER2-negative breast cancer.

 

Representative CDK4/6 inhibitors include Pfizer's Ibrance, Lilly's Verzenio, and Novartis's Kisqali.

 

Camizestrant applies Proteolysis-targeting chimera (PROTAC) technology to targeted protein degradation (TPD) drugs.

 

TPD is a next-generation drug candidate that harnesses the cell’s own protein degradation system to selectively eliminate target proteins.

 

While traditional small molecule drugs inhibit protein function, TPD drugs are known to offer superior therapeutic effects without resistance issues because they fundamentally degrade and eliminate the disease-causing proteins.

 

TPD drugs have the advantage of being able to target over 80% of disease-causing proteins that conventional small-molecule compounds cannot regulate.

 

The Phase III SERENA-6 trial evaluated the efficacy of maintaining the standard treatment regimen of aromatase inhibitors (anastrozole or letrozole) combined with CDK4/6 inhibitors or switching to camizestrant combination therapy in patients with HR-positive, HER2-negative advanced breast cancer who developed ESR1 mutations during first-line therapy.

 

According to the investigator assessment, the camizestrant combination therapy reduced the risk of disease progression or death by 56% compared with standard therapy.

 

The median progression-free survival (PFS) in the camizestrant combination therapy group was 16.0 months, significantly longer than the 9.2 months in the standard therapy group.

 

This improvement in PFS was consistent across various subgroups, including age, race, region, and the timing of ESR1 mutation detection and type.

 

Additionally, the camizestrant combination therapy was shown to significantly delay the onset of deterioration in quality of life.

 

According to exploratory analysis, the camizestrant combination therapy reduced the risk of deterioration in quality of life (global health status/QOL) by 47% compared to the aromatase inhibitors (AI) combination therapy.

 

At the time of this interim analysis, data on key secondary endpoints—including time from randomization to second disease progression or death (PFS2) and overall survival (OS)—were not yet mature.

 

However, the camizestrant combination therapy showed a trend toward prolonged treatment benefits based on PFS2.

 

The clinical trial will continue to evaluate OS, PFS2, and other key secondary endpoints in the future.

 

Presentation of SERENA-6 trial results at ASCO 2025 (Source: AZ).

Pfizer announced the results of its Phase III VERITAC-2 study of ‘vepdegestrant,' an oral SERD drug candidate developed in collaboration with Arvinas.

 

Pfizer acquired Arvinas' pipeline in 2021 and is currently conducting joint research.

 

Arvinas' platform PROTAC (PROTAC) was, for a period, widely regarded as synonymous with TPD technology.

 

The VERITAC-2 study is a Phase III clinical trial evaluating the efficacy of vepdegestrant in 624 patients with estrogen receptor (ER)+/HER2- advanced or metastatic breast cancer who have progressed on CDK4/6 inhibitors and endocrine therapy.

 

Patients were randomly assigned to the vepdegestrant or Faslodex group in a 1:1 ratio.

 

The primary endpoint was PFS, assessed by blinded independent central review (BICR) in patients with estrogen receptor 1 mutation (ESR1m) and all patients.

 

Overall survival (OS) was a key secondary endpoint.

 

Clinical trial results showed that the median PFS in the ESR1 mutation patient group treated with vepdegestrant was 5.0 months, compared to 2.1 months in the Faslodex group.

 

The vepdegestrant group showed a reduction in disease progression or death by 43%.

 

The most common treatment-emergent adverse events (TEAEs) in the vepdegestrant group were fatigue (15.6%), increased ALT (9.8%), increased AST (10.4%), and nausea (8.8%).

 

However, all these rates were lower than those in the Faslodex group.

 

The research team evaluated, “Vepdegestrant demonstrated overall good tolerability, with a low discontinuation rate due to adverse events.

 

These results support vepdegestrant’s potential as an oral treatment option for patients with previously treated ER+/HER2- advanced or metastatic breast cancer.