Safety and efficacy profile of Trastuzumab deruxtecan in solid cancer: pooled reanalysis based on clinical trials

Area of Science:

• Oncology
• Pharmacology
• Clinical Trials

Background:

• HER2-positive solid cancers represent a significant therapeutic challenge.
• Antibody-drug conjugates (ADCs) offer a targeted approach to cancer treatment.

Purpose of the Study:

• To evaluate the safety and efficacy of Trastuzumab deruxtecan (DS-8201a), a novel ADC, in patients with HER2-positive solid tumors.
• To assess the objective response rate (ORR) and progression-free survival (PFS) associated with DS-8201a treatment.

Main Methods:

• A systematic literature search was conducted across PubMed, Medline, and Ovid for clinical trials on DS-8201a.
• Safety was evaluated by calculating event rates for all adverse events (AEs).
• Efficacy was assessed by summarizing ORR and PFS.

Main Results:

• Common AEs (event rate >30%) included nausea, decreased appetite, vomiting, fatigue, anemia, decreased neutrophil count, alopecia, and diarrhea.
• High-grade AEs (grade 3 or more) with event rates >10% were decreased neutrophil count (20.3%), anemia (15.0%), and decreased white blood cell count (10.3%).
• Median PFS ranged from 9.0-22.1 months for breast cancer, 3.0-8.3 months for gastric cancer, and 4.1-11.9 months for other HER2-positive solid cancers. Median ORR was 37-79.9% for breast and gastric cancer, and 28.3-55% for other HER2-positive cancers.

Conclusions:

• Trastuzumab deruxtecan (DS-8201a) demonstrates significant activity in HER2-positive cancers, especially breast and gastric types.
• The most frequent adverse events are gastrointestinal and hematological.
• Decreased white blood cell count and appetite were identified as high-grade adverse events requiring monitoring.