VERITAC-2
Trial question
What is the effect of vepdegestrant in patients with ER+, HER2- advanced breast cancer?
Study design
Multi-center
Open label
RCT
Population
624 patients (621 female, 3 male).
Inclusion criteria: patients with ER+, HER2- advanced breast cancer who had received one previous line of CDK 4/6 inhibitor therapy plus one line of endocrine therapy.
Key exclusion criteria: advanced, symptomatic visceral spread at risk of life-threatening complications in short term; prior chemotherapy for advanced/metastatic disease; inadequate liver, kidney, or bone marrow function; active brain metastases; significant concomitant illness.
Interventions
N=313 vepdegestrant (at a dose of 200 mg PO once every day of each 28-day cycle).
N=311 fulvestrant (at a dose of 500 mg IM on day 1 and day 15 of cycle 1 and on day 1 of subsequent cycles).
Primary outcome
Median progression-free survival, population with ESR1 mutations
5 months
2.1 months
5.0 months
3.8 months
2.5 months
1.3 months
0.0 months
Vepdegestrant
Fulvestrant
Significant
increase ▲
Significant increase in median progression-free survival, population with ESR1 mutations (5 months vs. 2.1 months; HR 1.72, 95% CI 1.28 to 2.33).
Secondary outcomes
No significant difference in progression-free survival, overall population (3.8 months vs. 3.6 months; HR 1.2, 95% CI 0.99 to 1.45).
Significant increase in objective response, population with ESR1 mutations (18.6% vs. 4%; RR 4.64, 95% CI 1.63 to 13.22).
No significant difference in clinical benefit rate, overall population (34.3% vs. 28.7%; RR 1.18, 95% CI 0.92 to 1.51).
Safety outcomes
No significant differences in adverse events, serious adverse events.
Conclusion
In patients with ER+, HER2- advanced breast cancer who had received one previous line of CDK 4/6 inhibitor therapy plus one line of endocrine therapy, vepdegestrant was superior to fulvestrant with respect to median progression-free survival, population with ESR1 mutations.
Reference
Mario Campone, Michelino De Laurentiis, Komal Jhaveri et al. Vepdegestrant, a PROTAC Estrogen Receptor Degrader, in Advanced Breast Cancer. N Engl J Med. 2025 May 31. Online ahead of print.
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