2024 ESMO East: Dr Rizk Discusses the DESTINY-Breast12 Study
Presenter:
Victoria Rizk, MD, Tampa General Hospital Cancer Institute
Conference:
2024 ESMO East
In her presentation at the 2024 ESMO East conference, Dr Victoria Rizk from Tampa General Hospital Cancer Institute highlighted several abstracts from this year’s European Society for Medical Oncology (ESMO) Congress on the topic of metastatic breast cancer (mBC). Findings from the DESTINY-Breast12 Study, in particular, examined the efficacy of trastuzumab deruxtecan (T-DXd) for patients with Human epidermal growth factor receptor 2-positive (HER2+) mBC. Findings from the trial support the efficacy of T-DXd in treating patients with or without brain metastases, a population historically associated with poorer outcomes.
Background
HER2+ mBC accounts for approximately 15–20% of all breast cancers, and while HER2-targeted therapies have significantly improved survival, managing patients with brain metastases remains a clinical challenge. Results from smaller trials and retrospective analyses, such as TUXEDO-1 and DESTINY-Breast07, had shown as promising activity of T-DXd, an antibody -drug conjugate therapy, in HER2+ patients with brain metastases, which led to the design of the larger DESTINY-Breast-12 trial. DESTINY-Breast12 is the largest prospective study to evaluate the safety and efficacy of T-DXd in patients with HER2+ mBC, with stable or active brain metastases.
Study Design and Population
This was a phase 3b/4, multicenter, single-arm, open-label study which enrolled 504 patients with HER2+ mBC, dividing them into two cohorts:
· Patients with baseline brain metastases (n=263)
· Patients without brain metastases (n=241)
Eligibility criteria included patients age ≥18 years, documented HER2+ disease, an ECOG performance status of 0–1, and prior treatment with 2 or less HER2-targeted regimens in the metastatic setting. Patients with leptomeningeal disease were excluded.
Participants received T-DXd at a dose of 5.4 mg/kg intravenously every three weeks. The primary endpoint was progression-free survival (PFS) for the brain metastasis cohort, with secondary endpoints including overall survival (OS), central nervous system PFS (CNS PFS), objective response rate (ORR), and safety.
Main Results
Overall Efficacy
T-DXd demonstrated robust efficacy across all patient groups examined. The overall 12-month PFS was 61.6%, with a median PFS of 17.3 months. Notably, efficacy was consistent regardless of the presence or absence of brain metastases:
For patients with brain metastases: 12-month PFS was 61.6%, including 62.9% for those with stable brain metastases and 59.6% for those with active brain metastases.
For patients without brain metastases: 12-month PFS was 61.6%.
CNS-Specific Outcomes
Among patients with brain metastases, T-DXd achieved a CNS-specific PFS rate of 58.9% at 12 months. This included responses in patients with both stable and active brain metastases, demonstrating an effective control intracranial disease with T-DXd.
Objective Response Rates (ORR)
The ORR in patients with brain metastases was 62.7%, with complete responses observed in nearly 10% of patients. This response extended to CNS-specific lesions, with a CNS ORR of 71.7% observed in the trial.
Overall Survival (OS)
T-DXd also achieved a remarkable 12-month OS rate of 90.3% in patients with brain metastases and 90.6% in those without, demonstrating a consistent benefit of treatment across the cohorts examined.
Safety and Tolerability
The safety profile of T-DXd was consistent with that seen in previous studies. The most common side effects included nausea, fatigue, and neutropenia, which were reported at similar rates between the cohorts. Of particular interest was interstitial lung disease (ILD), a known adverse event associated with T-DXd. Grade 1–2 ILD occurred in approximately 9–10% of patients, with a smaller proportion experiencing grade 3–4 events. No new safety signals were identified.
Clinical Implications
DESTINY-Breast12 confirmed that T-DXd is a highly effective treatment option for HER2+ mBC, including those patients with either stable or active brain metastases. These findings are particularly impactful for patients with brain lesions, as there are limited options for systemic therapy with intracranial efficacy in this population. The durable CNS activity of T-DXd as seen in the study may help patients avoid or delay localized treatments such as radiation, which can help preserve quality of life and minimizing neurocognitive decline. The study also reinforces the importance of early detection and aggressive treatment of HER2+ mBC to optimize outcomes.
“With the DESTINY-Breast12 trial, we have compelling evidence that T-DXd offers meaningful systemic and intracranial control for patients with HER2-positive metastatic breast cancer, regardless of their brain metastasis status. This represents a pivotal step forward in addressing an unmet need for this challenging patient population.”
Conclusion
Results from the DESTINY-Breast12 trial establish T-DXd as a potentially transformative treatment for HER2+ mBC, for patients with or without brain metastases. With durable systemic and CNS efficacy, T-DXd is poised to become an essential component of care for this patient population. Careful monitoring for ILD remains essential to ensure patient safety during treatment. The findings from DESTINY-Breast12 mark an important milestone in advancing the care in HER2+ mBC, providing hope for both improving survival and preserving quality of life in these patients.
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Speaker Disclosure Information: Dr Rizk reported no relevant disclosures for this presentation.