npj Precision Oncology (Sep 2024)

A signal-seeking phase 2 study of Trastuzumab emtansine in tumours harbouring HER2 amplification or mutation

  • Subotheni Thavaneswaran,
  • Frank Lin,
  • John P. Grady,
  • David Espinoza,
  • Min Li Huang,
  • Sarah Chinchen,
  • Lucille Sebastian,
  • Maya Kansara,
  • Tony Mersiades,
  • Chee Khoon Lee,
  • Jayesh Desai,
  • Peter Grimison,
  • Michael Brown,
  • Michael Millward,
  • Rosemary Harrup,
  • Ken O’Byrne,
  • Adnan Nagrial,
  • Paul Craft,
  • John Simes,
  • Anthony M. Joshua,
  • David M. Thomas

DOI
https://doi.org/10.1038/s41698-024-00698-4
Journal volume & issue
Vol. 8, no. 1
pp. 1 – 10

Abstract

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Abstract This single-arm phase II non-randomised trial (ACTRN12619001265167) evaluated trastuzumab emtansine in solid cancers with HER2 amplification or mutation detected by comprehensive genomic profiling. The primary objective was objective response (OR), while secondary objectives included the time to progression (TTP) on study to TTP on prior therapy ratio, progression-free survival (PFS) and overall survival (OS). The cohort included 16 tumours with HER2 mutations (group 1) and 16 with HER2 amplification (group 2). After 17 months median follow-up, ORs occurred in 19% of group 1 (1 salivary gland carcinoma (SGC), 2 lung cancers) and 25% of group 2 (3 SGCs, 1 uterine carcinoma). Fourteen of 29 TTP-evaluable patients achieved a TTP ratio ≥1.3, including 10 without an OR. Median PFS and OS were 4.5 (95% CI 2.1–7.0) and 18.2 months (95% CI 8.1-not reached) respectively. Trastuzumab emtansine showed modest ORs and a favourable change in disease trajectory in select HER2-altered solid cancers.