Toxicity Markers to Trastuzumab-Deruxtecan (T-DXd) In Patients With Advanced Breast Cancer

Despite advanced in diagnosis and in the treatment management, advanced breast cancer (ABC) is still an incurable disease.

Recent pharmaceutical developments have changed treatment algorithms in MBC and have further improved the overall prognosis of patients which exploit the tumor-targeting activity of monoclonal antibodies to deliver at the tumor site potent chemotherapeutic agents that would otherwise be exceedingly toxic if delivered systemically.

Among them, new effective anticancer drugs, such as Trastuzumab-Deruxtecan (T-DXd), have revolutionized the clinical management of HER2-positive and HER2-low ABC. However, this drug is associated with a non-negligible rate of adverse events that can lead to treatment discontinuation and/or the onset of pneumonitis/interstitial lung disease (ILD), a potentially fatal adverse event.

The aim of the study is to identify and describe potentially predictive markers related to the onset of relevant T-DXd-related toxicities (both any grade ILD/pneumonitis and any toxicity of grade ≥3) in a population of patients treated with T-DXd according to standard clinical practice.

Inclusion criteria

• Male or female, aged at least 18 years.
• Histologically documented invasive breast cancer, either HER2-positive or HER2-low/ultralow.
• Candidate to receive T-DXd as per standard practice.
• Consent for the provision of blood samples for exploratory analyses.

Exclusion criteria

• Operable, non-metastatic breast cancer
• Unwillingness to provide additional blood draws