Antibody-drug conjugate shows promise in previously treated, HER2-positive gastric cancer

  • Shitara K & al.
  • N Engl J Med
  • 29 May 2020

  • curated by Jim Kling
  • Univadis Clinical Summaries
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Takeaway

  • Trastuzumab deruxtecan, an anti-HER2 antibody linked to a cytotoxic topoisomerase I inhibitor, led to improvements in response and OS as third-line therapy in patients with previously treated HER2-positive gastric cancer.

Why this matters

  • Existing third-line therapies have limited benefit in this population.

Study design

  • Open-label, multicenter, phase 2 trial in Japan and South Korea.
  • 187 patients were randomly assigned to trastuzumab deruxtecan or clinician's choice of therapy (DESTINY-Gastric01).
  • Funding: Daiichi Sankyo.

Key results

  • Trastuzumab deruxtecan is attached to a cytotoxic topoisomerase I inhibitor by a linker that is cleaved by enzymes overexpressed in tumor cells.
  • Compared with the clinician's choice group, the trastuzumab deruxtecan group had:
    • Higher objective response rate (51% vs 14%; P<.001>
    • Longer median duration of confirmed objective responses (11.3 vs 3.9 months).
    • Longer median OS (12.5 vs 8.4 months; HR for death, 0.59; P=.01).
    • Longer median PFS (5.6 vs 3.5 months; HR for disease progression or death, 0.47; 95% CI, 0.31-0.71).
  • 10 of 119 in the trastuzumab deruxtecan group had a complete response compared with none in the clinician's choice group.

Limitations

  • Open-label.