Analysis of T-DXd in HER2+ MBC from DESTINY-Breast01, -02, and -03 Trials

T-DXd has been approved for patients with HER2-positive unresectable or metastatic breast cancer following a previous anti-HER2-based treatment regimen in either the metastatic or (neo)adjuvant setting. This approval is based on the findings of the randomized phase 3 DESTINY-Breast03 study. According to a study, it has been observed that older patients with HER2-positive metastatic breast cancer (mBC) generally experience poorer efficacy and safety outcomes, irrespective of the specific treatment administered. The examination of outcomes in older patients undergoing treatment with T-DXd has not been conducted comprehensively. In this study, researchers presented an analysis of the efficacy and safety of T-DXd about age groups. The data for this analysis were obtained from the DESTINY-Breast01, DESTINY-Breast02, and DESTINY-Breast03 trials. Patients whose breast cancer had progressed while receiving trastuzumab emtansine (T-DM1) were recruited.

In DESTINY-Breast02, the effectiveness of trastuzumab deruxtecan (T-DXd) was compared to chemotherapy chosen by the treating physician. The study titled “DESTINY-Breast03” involved patients who had previously undergone treatment with trastuzumab and taxane. These patients were administered either T-DXd or T-DM1. Initially, in the clinical trials known as DESTINY-Breast01, DESTINY-Breast02, and DESTINY-Breast03, there were 44 individuals (23.9%), 85 individuals (20.9%), and 49 individuals (18.8%) respectively, who were aged 65 years or older and received T-DXd. At the Department of Clinical Oncology (DCO), the median pooled treatment duration with Trastuzumab Deruxtecan (T-DXd) was found to be 13.1 months, with a range of 0.7 to 44.0 months for patients below the age of 65. The median pooled treatment duration for patients aged 65 and above was 12.4 months, ranging from 0.7 to 45.1 months. The study found that treatment-emergent adverse events (TEAEs), specifically those of grade ≥3, and serious adverse events (AEs) were observed in different proportions among patients of different age groups. Among patients younger than 65, 99.6% experienced any-grade TEAEs, 53.6% experienced grade ≥3 TEAEs, and 24.3% experienced severe AEs. In contrast, among patients aged 65 years or older, 100% experienced any-grade TEAEs, 65.5% experienced grade ≥3 TEAEs, and 32.2% experienced severe AEs.

About 125 adverse events (18.7%) were observed in patients under 65. In comparison, 45 adverse events (25.4%) were reported in patients aged 65 years or older associated with T-DXd discontinuing. Drug-related interstitial lung disease/pneumonitis with any grade was observed in 11.8% of patients below 65 and 17.5% of patients aged 65 and above. Grade 5 events, the most severe category, were reported in 0.9% and 0.6% of patients below the age of 65 and aged 65 and above, respectively. Further evidence regarding the effectiveness and safety of the intervention will be provided. The findings from this comprehensive analysis provide additional evidence that T-DXd exhibits a favorable balance between benefits and risks in patients aged 65 years and older, albeit with a slightly elevated level of toxicity, as anticipated.

Source: https://meetings.asco.org/abstracts-presentations/219700

Clinical Trial: https://classic.clinicaltrials.gov/ct2/show/NCT03523585

Ian E. Krop, Hans Wildiers, Sara A. Hurvitz, Javier Cortes, Seock-Ah Im, Hiroji Iwata, Fabrice Andre, Cristina Saura, Sung-Bae Kim, Anton Egorov, Elton Mathias, Jillian Cathcart, Antonio Cagnazzo, Yingkai Cheng, Yeon Hee Park, Shanu Modi/An age-specific pooled analysis of trastuzumab deruxtecan (T‑DXd) in patients (pts) with HER2-positive (HER2+) metastatic breast cancer (mBC) from DESTINY-Breast01, -02, and -03./J Clin Oncol 41, 2023 (suppl 16; abstr 1006) DOI 10.1200/JCO.2023.41.16_suppl.1006