T-DXd Outperforms T-DM1 in IDFS/DFS for HER2+ Breast Cancer
Summary of Safety Findings from the Study: T-DXd vs. T-DM1 in HER2-Positive Early Breast Cancer
This text details the safety profiles of two treatment arms in a study comparing T-DXd and T-DM1 for high-risk, HER2-positive early breast cancer patients with residual disease after neoadjuvant therapy. Here’s a breakdown of the key safety findings:
Overall teaes (Treatment-Emergent Adverse Events):
* T-DXd: 96.2% of patients reported any-grade TEAEs, with 58.8% experiencing grade 3 or higher TEAEs. Serious TEAEs occured in 11.8%.
* T-DM1: 98.4% of patients reported any-grade TEAEs, with 51.9% experiencing grade 3 or higher TEAEs. Serious TEAEs occurred in 13.6%.
Specific Adverse Events (Most Common):
The most common TEAEs differed in frequency between the two arms:
| adverse Event | T-DXd (%) | T-DM1 (%) |
|---|---|---|
| Nausea | 71.3 | 29.3 |
| Constipation | 32.0 | 16.2 |
| decreased neutrophils | 31.6 | 14.4 |
| Vomiting | 31.0 | 9.0 |
| decreased WBC | 29.7 | 13.0 |
| Fatigue | 29.5 | 20.2 |
| Radiation Pneumonitis | 28.8 | 27.0 |
| Anemia | 28.3 | 17.0 |
| Increased AST | 25.6 | 50.2 |
| Increased ALT | 23.7 | 45.3 |
| Diarrhea | 23.2 | 8.6 |
| Decreased Platelets | 21.2 | 49.8 |
| Decreased Appetite | 20.0 | 10.0 |
| Headache | 15.8 | 20.7 |
| Arthralgia | 10.3 | 20.5 |
Key Safety Concerns:
* Drug-Related ILD (Interstitial Lung Disease)/Pneumonitis: Substantially higher rates were observed with T-DXd (9.6% any grade) compared to T-DM1 (1.6% any grade). Higher grades of ILD were also more frequent with T-DXd.
* Left ventricular Dysfunction: Slightly higher rates were observed with T-DXd (2.9% any grade) compared to T-DM1 (1.7% any grade).
* Discontinuation/interruptions/Reductions: T-DXd had higher rates of drug interruptions (41.1%) and dose reductions (26.6%) compared to T-DM1. Drug discontinuation occurred in 12.9% of T-DM1 patients, with 2.5% related to ILD/pneumonitis.
* Deaths: A small number of deaths occurred in each arm (0.6% for T-DXd and 0.6% for T-DM1) due to various causes.
Radiotherapy Timing:
The timing of adjuvant radiotherapy (sequential or concurrent) did not appear to influence the rates of drug-related ILD.
while T-DXd demonstrated superior efficacy, it was associated with a higher risk of certain adverse events, notably drug-related ILD, compared to T-DM1. The study authors concluded that the safety profile was “manageable” despite these concerns.