Trastuzumab deruxtecan in previously treated patients with HER2-positive metastatic breast cancer: updated survival results from a phase II trial (DESTINY-Breast01)

Abstract

Background: Primary analysis of the multicenter, open-label, single-arm, phase II 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 a median follow-up of 26.5 months (data cut-off 26 March 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 endpoint was confirmed objective response rate (ORR) by independent central review (ICR). Secondary endpoints included overall survival (OS), duration of response (DoR), progression-free survival (PFS), and safety.

Results: The ORR by ICR was 62.0% [95% confidence interval (CI) 54.5% to 69.0%] in patients who received T-DXd 5.4 mg/kg every 3 weeks (n = 184). Median OS was 29.1 months (95% CI 24.6-36.1 months). Median PFS and DoR were 19.4 months (95% CI 14.1-25.0 months) 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 one 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.

Keywords: HER2 positive; metastatic breast cancer; overall survival; trastuzumab deruxtecan.

Fig 1.

Patient disposition. Part 1 of the study consisted of 2 sequential stages: pharmacokinetics and dose finding. Based on these results, a dose of T-DXd 5.4 mg/kg was recommended for part 2 of the study. Part 2 consisted of an evaluation of the efficacy and safety of T-DXd in patients treated at the recommended dose who had tumor progression during or after the administration of T-DM1 (part 2a) and in those who had discontinued T-DM1 for reasons other than progressive disease (part 2b). AEs, adverse events; T-DM1, trastuzumab emtansine; T-DXd, trastuzumab deruxtecan.

Fig 2.

Efficacy analyses showing (A) overall survival, (B) progression-free survival, and (C) best percentage change from baseline in target lesions in DESTINY-Breast01 (N = 184). DCO March 26, 2021. Yellow line denotes progressive disease and green line denotes partial response. Blue line represents overall duration of response probability and gray lines represent 95% CI upper and lower limits. ^aBy independent central review. A total of 169 patients had both baseline and postbaseline target lesion assessments by independent central review and were included in this analysis. DCO, data cutoff; OS, overall survival; PFS, progression-free survival.

Fig 3.

Duration of Response. DCO March 26, 2021. Blue line represents overall DoR probability and gray lines represent 95% CI upper and lower limits. CR, complete response; DCO, data cutoff; DoR, duration of response; NE, not evaluable; PR, partial response.