Full Arvinas, Pfizer Data Reveal Promise and Limitations of Novel Breast Cancer Drug

Detailed results from a Phase 3 trial of vepdegestrant, an experimental breast cancer drug developed by Arvinas and Pfizer, have provided a clearer picture of the treatment's potential and limitations. The data, presented at the American Society of Clinical Oncology's annual meeting, show modest but significant benefits for a subset of patients with advanced breast cancer.

Vepdegestrant's Performance in ESR1-Mutated Breast Cancer

Vepdegestrant, an oral proteolysis-targeting chimera (PROTAC) drug, demonstrated improved efficacy compared to the standard treatment fulvestrant in patients with ESR1 mutations. In this subset:

• Median progression-free survival (PFS) was extended to 5 months with vepdegestrant, compared to 2.1 months with fulvestrant.
• The drug's performance in this group suggests potential as a new option for patients with ESR1-mutated breast cancer, which occurs in approximately 40% to 50% of patients undergoing first-line therapy for metastatic breast cancer.

However, the benefits were less pronounced in the overall study population:

• Median PFS was 3.8 months for vepdegestrant versus 3.6 months for fulvestrant across all 624 trial participants.
• These results indicate that vepdegestrant's use may be limited to a specific patient subgroup if approved.

Safety Profile and Treatment Challenges

The trial also revealed important safety considerations:

• 21% of participants taking vepdegestrant experienced severe or life-threatening side effects, compared to 17.6% on fulvestrant.
• Treatment discontinuation due to side effects was higher in the vepdegestrant group (2.9%) than in the fulvestrant group (0.7%).

Jane Lowe Meisel, co-director of breast medical oncology at the Winship Cancer Institute of Emory University School of Medicine, noted that while vepdegestrant is an "exciting option," the relatively short response duration for both drugs highlights "the need for combination therapies and continued development in this space."

Implications for Future Development

The mixed results have led to strategic changes in vepdegestrant's development:

• Pfizer and Arvinas plan to share the trial data with health regulators to support potential drug approval applications.
• However, the companies have scaled back their development plans, canceling two other planned Phase 3 trials.
• Arvinas has also reduced its workforce by one-third in response to these developments.

As the first PROTAC to advance through Phase 3 testing in advanced breast cancer, vepdegestrant represents a novel approach to treatment. Its potential approval could provide a valuable option for patients with ESR1-mutated breast cancer, a group that has historically been challenging to treat effectively.