Destiny Breast - 01 trial

Background

Phase II, single-arm, open-label registration study. 184 patients with HER2-positive metastatic breast cancer previously treated with trastuzumab emtansine (T-DM1). Median 6 prior lines for metastatic disease (range 2–27); prior T-DM1 100%, trastuzumab 100%, pertuzumab 65.8%, other anti-HER2 therapies 54.3%.

Interventions and follow up

Treatment: Trastuzumab deruxtecan (T-DXd) 5.4 mg/kg IV q3wk
Primary endpoint: Objective response rate (ORR) by independent review
mFollow up: 11.1 months

Results

ORR: 60.9%, 95% CI 53.4–68.0
Median duration of response: 14.8mo, 95% CI 13.8–16.9
mPFS: 16.4mo, 95% CI 12.7–not reached

Adverse events

Hematologic (grade ≥3): Decreased neutrophil count 20.7%, anemia 8.7%
Gastrointestinal: Nausea grade ≥3 7.6%
Pulmonary: Interstitial lung disease/pneumonitis 13.6% overall (grade 1–2 10.9%, grade 3–4 0.5%, grade 5 2.2%) by adjudication

Conclusions

Trastuzumab deruxtecan produced durable responses in heavily pretreated HER2-positive metastatic breast cancer after T-DM1. Interstitial lung disease, including fatal cases, mandates close pulmonary monitoring.

Key Limitations

Single-arm phase II with no comparator; efficacy benchmarked against historical data only. Interstitial lung disease in 13.6%, including grade 5 events in 2.2%, is a major safety concern requiring vigilance. Heavily pretreated population (median 6 prior lines) limits generalizability to earlier lines. Short follow-up at primary analysis (11.1mo).

Clinical Context

DESTINY-Breast01 supported accelerated FDA approval (Dec 2019) of T-DXd for HER2+ mBC after ≥2 prior anti-HER2 regimens. ESMO/ASCO guidelines now place T-DXd in second line based on the subsequent randomized DESTINY-Breast03. ILD monitoring (baseline imaging, prompt workup of pulmonary symptoms, dose interruption) is standard.

References