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.

Details

Title
A signal-seeking phase 2 study of Trastuzumab emtansine in tumours harbouring HER2 amplification or mutation
Author
Thavaneswaran, Subotheni 1   VIAFID ORCID Logo  ; Lin, Frank 2   VIAFID ORCID Logo  ; Grady, John P. 3 ; Espinoza, David 4 ; Huang, Min Li 5 ; Chinchen, Sarah 4 ; Sebastian, Lucille 4 ; Kansara, Maya 3 ; Mersiades, Tony 4 ; Lee, Chee Khoon 4 ; Desai, Jayesh 6   VIAFID ORCID Logo  ; Grimison, Peter 7 ; Brown, Michael 8 ; Millward, Michael 9 ; Harrup, Rosemary 10 ; O’Byrne, Ken 11 ; Nagrial, Adnan 12 ; Craft, Paul 13 ; Simes, John 4   VIAFID ORCID Logo  ; Joshua, Anthony M. 14 ; Thomas, David M. 15 

1  University of Sydney, NHMRC Clinical Trials Centre, Sydney, Australia (GRID:grid.1013.3) (ISNI:0000 0004 1936 834X); St Vincent’s Hospital, The Kinghorn Cancer Centre, Sydney, Australia (GRID:grid.437825.f) (ISNI:0000 0000 9119 2677); University of NSW, School of Clinical Medicine, Faculty of Medicine and Health, Sydney, Australia (GRID:grid.1005.4) (ISNI:0000 0004 4902 0432); Garvan Institute of Medical Research, Sydney, Australia (GRID:grid.415306.5) (ISNI:0000 0000 9983 6924) 
2  University of Sydney, NHMRC Clinical Trials Centre, Sydney, Australia (GRID:grid.1013.3) (ISNI:0000 0004 1936 834X); University of NSW, School of Clinical Medicine, Faculty of Medicine and Health, Sydney, Australia (GRID:grid.1005.4) (ISNI:0000 0004 4902 0432); Garvan Institute of Medical Research, Sydney, Australia (GRID:grid.415306.5) (ISNI:0000 0000 9983 6924); Kinghorn Centre for Clinical Genomics, Sydney, Australia (GRID:grid.415306.5) 
3  Garvan Institute of Medical Research, Sydney, Australia (GRID:grid.415306.5) (ISNI:0000 0000 9983 6924) 
4  University of Sydney, NHMRC Clinical Trials Centre, Sydney, Australia (GRID:grid.1013.3) (ISNI:0000 0004 1936 834X) 
5  University of NSW, School of Clinical Medicine, Faculty of Medicine and Health, Sydney, Australia (GRID:grid.1005.4) (ISNI:0000 0004 4902 0432); St Vincent’s Hospital, SydPath Department of Anatomical Pathology, Sydney, Australia (GRID:grid.437825.f) (ISNI:0000 0000 9119 2677) 
6  Peter MacCallum Cancer Centre, Melbourne, Australia (GRID:grid.1055.1) (ISNI:0000 0004 0397 8434) 
7  Chris O’Brien Lifehouse, Sydney, Australia (GRID:grid.419783.0) 
8  Royal Adelaide Hospital, Adelaide, Australia (GRID:grid.416075.1) (ISNI:0000 0004 0367 1221) 
9  Linear Clinical Research & University of Western Australia, Perth, Australia (GRID:grid.1012.2) (ISNI:0000 0004 1936 7910) 
10  Royal Hobart Hospital, Hobart, Australia (GRID:grid.416131.0) (ISNI:0000 0000 9575 7348) 
11  Princess Alexandra Hospital and Queensland University of Technology, Brisbane, Australia (GRID:grid.412744.0) (ISNI:0000 0004 0380 2017) 
12  Westmead Hospital, Sydney, Australia (GRID:grid.413252.3) (ISNI:0000 0001 0180 6477) 
13  The Canberra Hospital, Canberra, Australia (GRID:grid.413314.0) (ISNI:0000 0000 9984 5644) 
14  St Vincent’s Hospital, The Kinghorn Cancer Centre, Sydney, Australia (GRID:grid.437825.f) (ISNI:0000 0000 9119 2677); University of NSW, School of Clinical Medicine, Faculty of Medicine and Health, Sydney, Australia (GRID:grid.1005.4) (ISNI:0000 0004 4902 0432); Garvan Institute of Medical Research, Sydney, Australia (GRID:grid.415306.5) (ISNI:0000 0000 9983 6924) 
15  St Vincent’s Hospital, The Kinghorn Cancer Centre, Sydney, Australia (GRID:grid.437825.f) (ISNI:0000 0000 9119 2677); Garvan Institute of Medical Research, Sydney, Australia (GRID:grid.415306.5) (ISNI:0000 0000 9983 6924); University of New South Wales, Centre for Molecular Oncology, Sydney, Australia (GRID:grid.1005.4) (ISNI:0000 0004 4902 0432) 
Pages
195
Publication year
2024
Publication date
2024
Publisher
Nature Publishing Group
ISSN
2397768X
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41698-024-00698-4
ProQuest document ID
3102233794
Copyright
© The Author(s) 2024. This work is published under http://creativecommons.org/licenses/by-nc-nd/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.