Dr Krop on Age-Related Survival Outcomes With T-DXd in HER2+ Breast Cancer

Ian Krop, MD, PhD, associate director, Cancer Center, director, Clinical Trials Office, chief clinical research officer, Yale Cancer Center, discusses the use of fam-trastuzumab deruxtecan-nxki (Enhertu; T-DXd) across age groups in the phase 2 DESTINY-Breast01 (NCT03248492), phase 3 DESTINY-Breast02 (NCT03523585), and phase 3 DESTINY-Breast03 trials (NCT03529110) in patients with HER2-positive metastatic breast cancer.

T-DXd is currently approved for patients with HER2-positive, unresectable or metastatic breast cancer after a prior anti-HER2-based regimen in the metastatic or neoadjuvant setting. Although the current body of evidence continues to indicate that the agent is a highly effective standard of care for the general population, its performance in older patients has been under investigated. This area of research is especially important because older patients with HER2-positive disease are known to have poor safety and efficacy outcomes regardless of the treatment they receive, Krop explains.

A pooled analysis was designed to examine the survival outcomes with T-DXd in patients younger vs older than 65 years of age in all 3 DESTINY Breast trials. Patients in the DESTINY-Breast01 and DESTINY-Breast02 trials had previously progressed on ado-trastuzumab emtansine (T-DM1; Kadcyla). In DESTINY-Breast02, patients were given T-DXd or chemotherapy or physician’s choice of agent. Individuals in DESTINY-Breast03 were given T-DXd or T-DM1.

Descriptive efficacy analysis showed that median progression-free survival (PFS), 2-month landmark overall survival (OS), and confirmed overall response rates (ORR) with T-DXd were generally comparable in both age groups across all 3 studies, although no formal comparison was conducted. Further assessment of median OS in the DESTINY-Breast01 trial showed that T-DXd produced a median OS of 30.9 months in those 65 years of age or older vs 28.1 months for those younger than 65 years of age.

The safety profile of T-DXd was also acceptable in both age groups, although patients 65 years of age or older did experience a higher frequency of grade 3 or higher treatment-emergent adverse effects (TRAEs) in all 3 trials. The rate of treatment discontinuation due to AEs was numerically higher in the older patient group. Additionally, the rates of adjudicated interstitial lung disease were higher in those 65 years of age or older, although all cases of drug-related ILD were low grade.