Fam-Trastuzumab Deruxtecan-nxki (T-DXd): Real-World Data Confirms Trial Findings and Points to Broader Accessibility
Recent analysis of real-world data presented at the 43rd Annual Miami Breast Cancer Conference reinforces the positive tolerability profile of fam-trastuzumab deruxtecan-nxki (T-DXd) for patients with HER2-low metastatic breast cancer. The findings closely mirror those observed in the pivotal phase 3 DESTINY-Breast04 trial, suggesting that the benefits seen in clinical settings are translating effectively into everyday practice.
Managing Toxicity: A Focus on Interstitial Lung Disease
Discontinuation rates due to toxicity were consistent between the real-world cohort (15%) and the DESTINY-Breast04 trial (16.2%). Interstitial lung disease (ILD)/pneumonitis remains the most common reason for stopping treatment, but the incidence was slightly lower in the real-world setting (10.0% vs. 12.1% in the trial). This suggests that clinicians are becoming increasingly adept at recognizing and managing this potential side effect.
Treatment delays or holds were frequently linked to ILD/pneumonitis, but also to nausea/vomiting and neutropenia. When ILD/pneumonitis does occur, corticosteroids are the primary intervention, utilized in 80% of cases. Other management strategies include treatment holds, supportive care, and, in some instances, hospitalization.
Treatment Patterns and Patient Characteristics
The real-world cohort largely reflected the patient population studied in DESTINY-Breast04, with 77.0% having hormone receptor-positive disease and nearly 40% having at least one comorbidity. Most patients had advanced disease, with stage IV representing 24.7% of the cohort. Importantly, the majority (72.0%) had no impairment in performance status.
Interestingly, T-DXd is not yet widely used as a first-line treatment, with only 3.7% of patients receiving it in that setting. Instead, it’s being utilized more frequently in later lines of therapy – particularly the third (23.3%), fourth (20.3%), and fifth (15.7%) lines – suggesting it’s becoming a valuable option for patients who have exhausted other treatments.
The Future of HER2-Low Breast Cancer Treatment
The consistency between trial data and real-world experience is a strong indicator of T-DXd’s potential to become a standard of care for HER2-low metastatic breast cancer. As clinicians gain more experience with the drug, and as diagnostic capabilities improve to accurately identify HER2-low patients, we can expect to spot increased utilization, potentially even in earlier lines of therapy.
Further research is focused on identifying biomarkers that can predict which patients are most likely to benefit from T-DXd and which are at higher risk of developing ILD/pneumonitis. This personalized approach will be crucial for maximizing the drug’s efficacy and minimizing its toxicity.
Did you know? HER2-low breast cancer represents a significant unmet need, as these tumors don’t express enough HER2 to qualify for traditional HER2-targeted therapies, but may still benefit from a targeted approach like T-DXd.
Expanding Applications: Beyond Metastatic Disease
The success of T-DXd in metastatic HER2-low breast cancer is paving the way for investigations in other settings, including early-stage disease. The DESTINY-Breast05 trial demonstrated a significant reduction in the risk of disease recurrence or death with T-DXd following neoadjuvant therapy in high-risk HER2-positive early breast cancer. This suggests a potential role for T-DXd in a curative-intent setting.
research is ongoing to explore the efficacy of T-DXd in other HER2-expressing cancers, including gastric cancer and non-modest cell lung cancer.
FAQ
Q: What is the most common side effect of T-DXd?
A: Interstitial lung disease (ILD)/pneumonitis is the most common serious side effect.
Q: Is T-DXd used as a first-line treatment?
A: Currently, it’s more commonly used in later lines of therapy, but its leverage in earlier lines is being investigated.
Q: What is HER2-low breast cancer?
A: It’s a type of breast cancer that expresses a low level of the HER2 protein, making it ineligible for traditional HER2-targeted therapies.
Pro Tip: Early detection and prompt reporting of any respiratory symptoms to your healthcare provider are crucial for managing potential ILD/pneumonitis associated with T-DXd.
Learn more about breast cancer treatment options at the National Cancer Institute.
Have questions about T-DXd or HER2-low breast cancer? Share your thoughts in the comments below!
