A signal-seeking phase 2 study of Trastuzumab emtansine in tumours harbouring HER2 amplification or mutation.
Subotheni ThavaneswaranFrank Po-Yen LinJohn P GradyDavid EspinozaMin Li HuangSarah ChinchenLucille SebastianMaya KansaraTony MersiadesChee Khoon LeeJayesh DesaiPeter GrimisonMichael BrownMichael MillwardRosemary HarrupKen O'ByrneAdnan NagrialPaul CraftR John SimesAnthony M JoshuaDavid M ThomasPublished in: NPJ precision oncology (2024)
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.
Keyphrases
- metastatic breast cancer
- free survival
- phase ii
- open label
- epidermal growth factor receptor
- nucleic acid
- positive breast cancer
- clinical trial
- end stage renal disease
- ejection fraction
- newly diagnosed
- peritoneal dialysis
- single cell
- randomized controlled trial
- placebo controlled
- mesenchymal stem cells
- double blind
- label free
- patient reported