SABCS 2019 – HER2+ breast cancer: trastuzumab deruxtecan shines in DESTINY trial


  • Ben Gallarda
  • Univadis
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Takeaway

  • A 14.8-month duration of response (DoR) tops the list of positive findings for the antibody-drug conjugate trastuzumab deruxtecan under evaluation for human epidermal growth factor receptor 2 (HER2)-positive breast cancer in the DESTINY-Breast01 trial.
  • Median PFS was 16.4 months.  
  • Interstitial lung disease (ILD), including 4 deaths, remains a concern.

Why this matters

  • Lead investigator Ian Krop, Associate Chief of Division of Breast Oncology at the Dana-Farber Cancer Institute, said the data “demonstrate the potential for trastuzumab deruxtecan to establish a new standard of care for advancer HER2+ breast cancer.”
  • He noted the PFS and DoR are “roughly double or triple” that for previous candidates in similar clinical populations, he also said more research into related risk factors for ILD is needed.
  • Carlos Arteaga, co-director of SABCS and director of the Harold C. Simmons Comprehensive Cancer Center at the University of Texas, Southwestern, called the results “fantastic” and predicted that trials involving earlier-stage disease would show “even greater” effect.

Key results

  • 60.9% of patients (95% CI, 53.4%-68.0%; 112 patients) had a response to therapy, per the intention-to-treat analysis.
  • Median treatment duration: 10.0 (range, 0.7-20.5) months.
  • Median DoR: 14.8 (95% CI, 13.8-16.9) months.
  • Median PFS duration: 16.4 months (95% CI, 12.7-not reached).
  • Response rates were similar across subgroups, including those with brain metastases.
  • Grade ≥3 adverse events (AEs): neutropenia (febrile neutropenia
  • 13.6% of patients reported ILD, with 4 deaths ruled as drug related.
  • No clinically significant cardiac toxicity.

Study design

  • Open-label, multicenter phase 2 trial (part 2 of trial), 184 patients with unresectable/metastatic HER2+ disease and a median of 6 prior lines of therapy.
  • Funding: Daiichi Sankyo; AstraZeneca.

Limitations

  • Wide CIs for results in subgroup with brain metastases.

Note