New Treatment Shows Significant Survival Benefits in HER2+ Breast Cancer

Patients with high-risk, HER2-positive breast cancer have shown promising results from a new treatment, fam-trastuzumab deruxtecan-nxki (T-DXd), which offers a statistically significant improvement in invasive disease-free survival (IDFS) compared to ado-trastuzumab emtansine (T-DM1). Interim findings from the phase 3 DESTINY-Breast05 trial were presented at the 2025 ESMO Congress, revealing that T-DXd led to a remarkable 53% reduction in the risk of invasive disease or death.

In the study, which included 1,635 patients, those treated with T-DXd (n = 818) experienced an IDFS rate of 92.4%, compared to 83.7% for those receiving T-DM1 (n = 817). The hazard ratio was 0.47 (95% CI, 0.34-0.66; P < .0001), indicating a strong benefit for the T-DXd group. Dr. Charles E. Geyer Jr., a leading researcher and professor of medicine at the University of Pittsburgh Medical Center, emphasized that the benefits of T-DXd were consistent across various demographics, including age, hormone receptor status, and previous treatment types. “Patients benefited from T-DXd irrespective of age cohorts, region of accrual, hormone receptor status, disease status at presentation, post-therapy pathologic nodal status, and the sequence or usage of radiation therapy,” he stated during the presentation.

The DESTINY-Breast05 trial specifically targeted patients who had residual invasive disease after neoadjuvant therapy, categorizing them as having high-risk disease. This includes individuals with inoperable early breast cancer or operable cases with axillary node-positive disease following neoadjuvant therapy. All participants had to have centrally confirmed HER2-positive disease and an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

Patients were randomly assigned to receive either intravenous T-DXd at 5.4 mg/kg or T-DM1 at 3.6 mg/kg, both administered every three weeks for 14 cycles. The primary endpoint of the trial was IDFS, while disease-free survival (DFS) served as a key secondary endpoint. Other secondary outcomes included overall survival (OS), distant recurrence-free interval (DRFI), and brain metastasis-free interval (BMFI).

Of the patients treated with T-DXd, 27.7% discontinued therapy due to adverse effects or other reasons, while 72.3% completed the treatment regimen. In the T-DM1 group, 23.7% discontinued for similar reasons, with 76.3% completing treatment. The median study duration was approximately 30 months for both groups.

Results indicated that T-DXd not only improved IDFS but also showed lower rates of distant and local recurrences. The three-year DFS rates were 92.3% for T-DXd versus 83.5% for T-DM1, with a hazard ratio of 0.47 (95% CI, 0.34-0.66; P < .0001). Additionally, the trial reported significant benefits in DRFI, BMFI, and OS for patients receiving T-DXd. Adverse events were monitored closely, with 99.5% of patients in the T-DXd arm reporting treatment-emergent adverse events (TEAEs), including manageable cases of interstitial lung disease. In contrast, 98.4% of patients in the T-DM1 arm experienced TEAEs, with a slightly lower incidence of serious adverse events.

Dr. Geyer concluded that the findings from the DESTINY-Breast05 trial position T-DXd as a potential new standard of care for patients with high-risk, HER2-positive early breast cancer and residual invasive disease following neoadjuvant therapy. He noted the critical need for improved post-neoadjuvant treatment options in this patient population.

The results of this trial further underscore the importance of ongoing research in the field of oncology and the need for innovative treatment strategies to enhance patient outcomes in challenging cancer diagnoses.