A signal-seeking phase 2 study of Trastuzumab emtansine in tumours harbouring HER2 amplification or mutation
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.
Authors
- Paul Craft
- Sarah Chinchen
- Lucille Sebastian
- Rosemary Anne Harrup (ORCID: https://orcid.org/0000-0002-9770-2791)
- Michael D. Brown (ORCID: https://orcid.org/0000-0002-0370-8077)
- Min Huang
- Peter Grimison (ORCID: https://orcid.org/0000-0002-2653-1657)
- Kenneth J. O’Byrne (ORCID: https://orcid.org/0000-0002-6754-5633)
- Frank Lin (ORCID: https://orcid.org/0000-0001-9250-6874)
- John P. Grady (ORCID: https://orcid.org/0000-0001-9667-3872)
- Subotheni Thavaneswaran (ORCID: https://orcid.org/0000-0002-8946-6709)
- David M. Thomas (ORCID: https://orcid.org/0000-0002-2527-5428)
- Adnan Nagrial (ORCID: https://orcid.org/0000-0003-0275-2479)
- Chee Khoon Lee (ORCID: https://orcid.org/0000-0003-2955-9820)
- Jayesh Desai (ORCID: https://orcid.org/0000-0003-4246-9344)
- Michael Millward (ORCID: https://orcid.org/0000-0002-1744-1617)
- Maya Kansara (ORCID: https://orcid.org/0000-0003-1908-3574)
- Anthony M. Joshua (ORCID: https://orcid.org/0000-0001-5159-4580)
- Tony Mersiades
- David Espinoza
- John Simes
Institutions
- The University of Sydney (AU)
- New South Wales Department of Health (AU)
- Royal Adelaide Hospital (AU)
- Garvan Institute of Medical Research (AU)
- Queensland University of Technology (AU)
- Peter MacCallum Cancer Centre (AU)
- Princess Alexandra Hospital (AU)
- Canberra Hospital (AU)
- Royal Hobart Hospital (AU)
- Westmead Hospital (AU)
- UNSW Sydney (AU)
- St Vincent's Hospital Sydney (AU)
- Chris O’Brien Lifehouse (AU)
- St Vincent’s Private Hospital Sydney (AU)
- The Kinghorn Cancer Centre (AU)
- Linear Clinical Research (AU)
- National Health and Medical Research Council (AU)
Publication Details
- Journal
- npj Precision Oncology
- Published
- 2024-09-09
- DOI
- https://doi.org/10.1038/s41698-024-00698-4
- Citations
- 5
- Primary Topic
- HER2/EGFR in Cancer Research
- Type
- article
- Field-Weighted Citation Impact
- 1.41
Funders
- Office of Health and Medical Research
- Australian Institute of Health and Welfare, Australian Government