Human epidermal growth factor receptor 2 targeted therapy in endometrial cancer: Clinical and pathological perspectives

Table 1 Human epidermal growth factor receptor 2 overexpression and gene amplification in endometrial cancer

Histological type	HER2 overexpression	HER2 gene amplification	Ref.
Overall	4%-69%	18%-80%	[19,45,55]
Endometrioid (low grade)	rare	rare	[29,45]
Endometrioid (high grade)	8%-31%	15%-29%	[29,45]
Serous carcinoma	20%-60%	13%-29%	[29,42,43,45]
Clear cell carcinoma	33%-70%	22%-50%	[29,55]
Carcinosarcoma	0-25%	13%-20%	[38,48-51]

Table 2 Human epidermal growth factor receptor 2-targeted therapies for uterine serous carcinoma and carcinosarcoma

Trial	Phase	Participants	Treatment	Efficacy/indentifer
GOG181B[55]	II	HER2-positive EC (n = 33, endometrioid: 13, serous: 11, clear: 3, others: 6)	Trastuzumab	ORR 0%, mPFS 1.84 mo, mOS 7.8 mo
GOG229D[56]	II	Persistent or recurrent EC (n = 31, endometrioid: 16, serous: 7, clear: 3, others: 5, HER2-positive: n = 2)	Lapatinib	mPFS 1.82 mo, mOS 7.33 mo
Fader et al[46,57]	II	HER2-positive USC (n = 61)	carboplatin+paclitaxel+trastuzumab vs carboplatin+paclitaxel	mPFS 12.9 mo vs 8.0 mo, mOS 29.6 vs 24.4 mo
MyPathway[25]	Phase IIa Multiple basket study	Solid tumor(HER2-positive EC, n = 7)	Trastuzumab+pertuzumab	ORR 0%(EC)
Li et al[59]	II	HER2 amplified cancer (endometrial cancer: n = 18)	Trastuzumab emtansine	Endometrial cancers: CR 2, PR 2
DESTINY-PanTumor02[77]	II	HER2 expressing tumor (urothelial, biliary tract, cervical, endometrial, ovarian, pancreatic, rare tumors)	Trastumab deruxtecan	NCT04482309
Veneris[78]	I	HER2-positive USC	Trastuzumab deruxtecan+olaparib	NCT04585958
Banerji et al[61]	I	Dose-expansion cohort: HER2-positive breast, gastric, urothelial, endometrial cancer	SYD-985 (Trastuzumab duocarmazine)	Endometrial cancer: ORR 39%, mPFS 4.3 mo
Koper[79]	I	HER2-positive solid tumor	SYD-985 (Trastuzumab duocarmazine)+Niraparib	NCT04235101
Hendriks[80]	II	HER2-positive endometrial cancer	SYD-985 (Trastuzumab duocarmazine)	NCT04205630
STATICE[52]	II	HER2-positive UCS	Trastuzumab deruxtecan	UMIN00002956 (NCCH1615)
Makker[81]	II	HER2-positive endometrial cancer, UCS	ZW25	NCT04513665
Ramos[82]	II	HER2-positive solid tumors	Tucatinib and trastuzumab	NCT04579380

EC: Endometrial cancer; USC: Uterine serous carcinoma; UCS: Uterine carcinosarcoma; CR: Complete response; mOS: Median overall survival; mPFS: Median progression-free survival; ORR: Objective response rate; PR: Partial response.