HER2+ Metastatic Breast Cancer (MBC) Updates from San Antonio Breast Cancer Symposium
Recent data from the 2025 San Antonio Breast Cancer Symposium indicates a significant advancement in treating HER2-positive metastatic breast cancer.
HER2CLIMB-05
The HER2CLIMB-05 Phase 3 trial investigated the impact of adding tucatinib to the first-line maintenance regimen (trastuzumab and pertuzumab). The key findings include:
- Survival Gains: The triple-drug regimen extended median progression-free survival (PFS) to 24.9 months, compared to 16.3 months for the placebo group - a gain of 8.6 months.
- Hormone Receptor (HR) Status: While all subgroups benefited, the impact was most pronounced in HR-negative patients (a 12.3-month improvement) compared to HR-positive patients (a 6.9-month improvement).
- Neurological Impact: In a promising exploratory analysis, tucatinib nearly doubled the time patients with existing brain metastases remained stable (8.5 months vs. 4.3 months), suggesting a delay in CNS progression.
Comparative Context: HER2CLIMB-05 vs. PATINA
The findings were weighed against the PATINA trial, which utilizes palbociclib for HR+/HER2+ patients.There were several important distinctions between the two studies:
- Endocrine Therapy (ET) Gap: In HER2CLIMB-05, fewer than half of the HR-positive patients received endocrine therapy during maintenance, despite it being the standard of care. In contrast, all PATINA participants received ET.
- Patient Profiles: The PATINA trial generally featured a lower-risk population, with fewer cases of de novo disease and significantly fewer brain metastases at the start of the study compared to HER2CLIMB-05.
- PFS Benchmarks: While PATINA showed a higher median PFS (44.3 months), the different patient demographics and the universal use of ET make a direct comparison difficult.
Read the abstract here:
https://sabcs.org/events/2025/general-session-1/
DESTINY-Breast09 (DB09)
The DESTINY-Breast09 (DB09) trial results (https://www.nejm.org/doi/10.1056/NEJMoa2508668) presented in 2025 highlight a significant trade-off between increased efficacy and heightened toxicity in the first-line treatment of HER2-positive metastatic breast cancer.
Clinical Efficacy: A New Benchmark
The study compared a combination of Trastuzumab deruxtecan (T-DXd) plus pertuzumab against the current gold standard (taxane, trastuzumab, and pertuzumab).
- Progression-Free Survival (PFS): The T-DXd regimen significantly outperformed the standard therapy, reaching a median PFS of 40.7 months vs. 26.9 months.
- Impact: This represents a nearly 1.5x increase in the duration of time patients remained stable on treatment.
Quality of Life and Side Effects
While the efficacy is record-breaking, patient-reported outcomes (PROs) and safety data presented at the 2025 San Antonio Breast Cancer Symposium (SABCS) suggest that the regimen comes with distinct challenges:
- Gastrointestinal Burden: Patients on the T-DXd regimen reported higher rates of nausea, vomiting, loss of appetite, and constipation.
- Symptom Trade-offs: On the positive side, T-DXd caused fewer skin issues, mucosal problems (like nosebleeds), and limb swelling compared to the standard taxane-based therapy.
- General Wellbeing: Interestingly, there were no significant differences between the two groups regarding fatigue, pain levels, or overall physical functioning.
Interstitial Lung Disease (ILD)
The most serious finding involved Interstitial Lung Disease (ILD) or pneumonitis, which remains a primary concern for T-DXd:
- Incidence: 12.1% of patients in the T-DXd group developed ILD, compared to 1.0% in the standard care group. 2
Read the abstract:
https://sabcs.org/events/2025/poster-session-5/
PATINA Secondary Analysis
Recent findings from a secondary analysis of the PATINA trial offer a promising strategy for managing HR+/HER2+ metastatic breast cancer, specifically regarding the prevention of brain metastases.
Given that nearly half of all patients with HER2-positive metastatic disease eventually experience cancer spread to the central nervous system (CNS), these results represent a meaningful shift in preventative care.
The Role of Palbociclib in CNS Protection
The study explored whether adding palbociclib (a CDK4/6 inhibitor) to standard endocrine therapy and first-line maintenance treatment could stall or prevent brain involvement. The data suggests a protective effect:
- Reduced Risk: Over a 36-month period, the rate of CNS-related progression or death was significantly lower in the palbociclib group (13.4%) compared to the control group (19.9%).
- Preventative Value: For patients who entered the trial without any existing brain metastases, the risk of developing them or dying was reduced to 13.0%, whereas the control group saw a risk of 19.2%.
Read the abstract: