Drug Update · Oncology

FDA Approves VEPPANU for ESR1‑Mutant Advanced Breast Cancer: PFS HR 0.57

July 12, 2026

Trial

VERITAC-2

Population (ESR1-mutated)

VEPPANU N=136; Fulvestrant N=134

Primary result (PFS)

Median 5.0 vs 2.1 months; HR 0.57 (95% CI 0.42-0.77); p=0.0001

Objective response rate

19% vs 4% (VEPPANU vs fulvestrant) among measurable disease

Recommended dose

200 mg orally once daily with food

Clinical Perspective

Oncologists and oncology pharmacists treating ER-positive, HER2-negative advanced breast cancer should consider VEPPANU for patients whose tumors harbor ESR1 mutations documented by an FDA-authorized test and who have progressed after at least one line of endocrine therapy, including prior CDK4/6 inhibitor exposure as in VERITAC-2 ^[1]. The trial data support using VEPPANU in the biomarker-defined ESR1-mutated subgroup where median PFS improved from 2.1 to 5.0 months and ORR was higher versus fulvestrant ^[1]. clinicians must ensure appropriate baseline and follow-up ECG and electrolyte assessment because the label specifies management steps for QTc prolongation, and dose modifications are defined for cardiac-safety events ^[1].

Dr. Meera Pillai · Oncology

The FDA approved VEPPANU for adults with ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer on 2026-05-01 based on VERITAC-2, which showed a progression-free survival benefit in patients with ESR1-mutated tumors: median PFS 5.0 months versus 2.1 months with fulvestrant (HR 0.57; 95% CI 0.42-0.77; p=0.0001) ^[1]. The approval specifies selection by an FDA-authorized test for ESR1 mutation and a recommended dose of 200 mg orally once daily with food ^[1]. Clinicians should consult current prescribing information for complete dosing guidance.

Clinical Context

VEPPANU is a heterobifunctional protein degrader indicated for ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer, as detected by an FDA-authorized test ^[1]. The approval labels VEPPANU as a targeted oral therapy given once daily with food at 200 mg, intended for patients with disease progression following at least one line of endocrine therapy ^[1]. Clinicians should consult current prescribing information for full dosing guidance. VERITAC-2 enrolled patients previously treated with endocrine therapy and a CDK4/6 inhibitor; ESR1 mutational status was assessed by plasma ctDNA testing centrally or locally ^[1]. The indication requires an FDA-authorized diagnostic to document ESR1 mutation before initiating therapy ^[1].

Key Findings

The randomized VERITAC-2 trial evaluated VEPPANU 200 mg orally once daily versus fulvestrant 500 mg intramuscularly in patients with ER-positive, HER2-negative advanced or metastatic breast cancer; randomization was 1:1 and stratified by ESR1 mutation status and visceral metastasis ^[1]. Clinicians should consult current prescribing information for full dosing guidance. In the prespecified cohort with ESR1-mutated tumors (VEPPANU N=136; fulvestrant N=134), blinded independent central review reported median PFS 5.0 months (95% CI 3.7, 7.4) with VEPPANU versus 2.1 months (95% CI 1.9, 3.5) with fulvestrant ^[1]. The hazard ratio for progression was 0.57 (95% CI 0.42, 0.77), with a one-sided p-value of 0.0001 by stratified log-rank test ^[1]. Confirmed objective response rate among patients with measurable disease was 19% (95% CI 12, 27) with VEPPANU versus 4% (95% CI 1.6, 10) with fulvestrant; there were no complete responses in either arm in this subgroup ^[1]. Overall survival data were immature at the PFS analysis with 16% of deaths observed in the ESR1-mutated cohort ^[1].

Safety & Tolerability

VEPPANU labeling includes guidance for QTc prolongation monitoring and management; explicit reported concerns include QTc prolongation thresholds and arrhythmia risks ^[1].
The product label provides dose modification and management recommendations when QTc exceeds 480 ms or increases >60 ms from baseline, and for QTc >500 ms; reversible causes such as hypokalemia and hypomagnesemia are to be identified and corrected ^[1].
The label specifies permanent discontinuation for torsade de pointes, polymorphic ventricular tachycardia, or signs/symptoms of serious arrhythmia ^[1].

(Only adverse-event or safety management items explicitly named in the provided source excerpts are listed above.)

Study Design

VERITAC-2 was a randomized, open-label, active-controlled, multicenter trial that enrolled 624 patients with ER-positive, HER2-negative advanced or metastatic breast cancer, 270 of whom had ESR1-mutated tumors per ctDNA testing ^[1]. Patients were randomized 1:1 to VEPPANU 200 mg orally once daily (N=313) or fulvestrant 500 mg intramuscularly (N=311), with stratification by ESR1 mutation status and visceral metastasis; pre-menopausal/perimenopausal patients received a GnRH agonist ^[1]. Clinicians should consult current prescribing information for full dosing guidance. The primary efficacy endpoint reported for the ESR1-mutated cohort was progression-free survival by blinded independent central review; secondary outcomes included overall survival and objective response rate ^[1].

FAQ

Q1 What is VEPPANU approved for?

VEPPANU is approved for the treatment of adults with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative, ESR1-mutated advanced or metastatic breast cancer, when the ESR1 mutation is detected by an FDA-authorized test, for patients with disease progression following at least one line of endocrine therapy. The approval specifies selection by an FDA-authorized diagnostic test and is based on VERITAC-2 efficacy results in the ESR1-mutated subgroup.

Q2 How does VEPPANU work?

VEPPANU is described in the prescribing information as a heterobifunctional protein degrader targeting the estrogen receptor; the label characterizes the agent as a targeted degrader intended to reduce estrogen receptor signaling in ER-positive breast cancer with ESR1 mutations. The approval and mechanism are described in the clinical indication and mechanism language of the product labeling.

Q3 What is the recommended dose of VEPPANU?

The recommended dosage of VEPPANU is 200 mg taken orally once daily with food until disease progression or unacceptable toxicity. The prescribing information instructs to swallow tablets whole and to follow dose interruption, reduction to 100 mg once daily, or permanent discontinuation rules for adverse reactions as specified in the label. Clinicians should consult current prescribing information for complete dosing guidance.

Q4 What are the most common side effects?

[Information] was not available in the provided source excerpts.

References

FDA (Prescribing Information) — FDA prescribing information — VEPPANU

FDA Approves VEPPANU for ESR1‑Mutant Advanced Breast Cancer: PFS HR 0.57

FDA Approves VEPPANU for ESR1‑Mutant Advanced Breast Cancer: PFS HR 0.57

Clinical Perspective

Clinical Context

Key Findings

Safety & Tolerability

Study Design

FAQ

References

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