Trastuzumab Deruxtecan in Previously Treated Patients With HER2-Positive Metastatic Breast Cancer: Updated Survival Results From a Phase 2 Trial (DESTINY-Breast01)

by Selleckchem | Jan 23 2024

Background: Primary analysis of the multicenter, open-label, single-arm, phase 2 DESTINY-Breast01 trial (median follow-up, 11.1 months) demonstrated durable antitumor activity with trastuzumab deruxtecan (T-DXd) in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (mBC) previously treated with trastuzumab emtansine (T-DM1). We report updated cumulative survival outcomes with median follow-up of 26.5 months (data cutoff, March 26, 2021).

Patients and methods: Patients with HER2-positive mBC resistant or refractory to T-DM1 received T-DXd 5.4 mg/kg intravenously every 3 weeks until disease progression, unacceptable adverse events, or withdrawal of consent. The primary end point was confirmed objective response rate by independent central review. Secondary end points included overall survival, duration of response, progression-free survival, and safety.

Results: The objective response rate by independent central review was 62.0% (95% CI, 54.5-69.0) in patients who received T-DXd 5.4 mg/kg every 3 weeks (n = 184). Median overall survival was 29.1 months (95% CI, 24.6-36.1). Median progression-free survival and duration of response were 19.4 months (95% CI, 14.1-25.0) and 18.2 months (95% CI, 15.0 months-not evaluable), respectively. Drug-related treatment-emergent adverse events (TEAEs) were observed in 183 patients (99.5%), and 99 patients (53.8%) had 1 or more grade ≥ 3 TEAEs. Adjudicated drug-related interstitial lung disease/pneumonitis occurred in 15.8% of patients (n = 29), of which 2.7% (n = 5) were grade 5.

Conclusions: These updated results provide further evidence of sustained antitumor activity of T-DXd with a consistent safety profile in heavily pretreated patients with HER2-positive mBC.

Comments:

The DESTINY-Breast01 trial results you've mentioned show promising outcomes for patients with HER2-positive metastatic breast cancer (mBC) resistant or refractory to trastuzumab emtansine (T-DM1) who were treated with trastuzumab deruxtecan (T-DXd). The study reported durable antitumor activity with T-DXd, even in heavily pretreated individuals.

Key findings from the updated analysis with a longer follow-up of 26.5 months include:
- An objective response rate of 62.0% among patients who received T-DXd 5.4 mg/kg every 3 weeks.
- A median overall survival of 29.1 months, indicating a significant extension in survival from the previous analysis.
- Median progression-free survival of 19.4 months and a duration of response of 18.2 months, demonstrating sustained benefit from treatment.
- Safety observations indicated that drug-related treatment-emergent adverse events were observed in almost all patients, with over half experiencing grade ≥ 3 adverse events.
- Adjudicated drug-related interstitial lung disease/pneumonitis occurred in 15.8% of patients, with 2.7% being severe (grade 5).

These results suggest continued and substantial antitumor activity of T-DXd with a generally consistent safety profile in this challenging patient population. The study reinforces the potential of T-DXd as a viable treatment option for those with HER2-positive mBC who have previously been treated with T-DM1.

The findings underline both the efficacy and safety considerations of T-DXd, particularly emphasizing the need for vigilant monitoring and management of potential lung-related adverse events while acknowledging its significant antitumor effects.