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HER2 擴增 藥物選擇

# HER2 基因擴增／過度表現

# HER2 與 EGFR 同屬於相同的訊號激酶受體家族，且已在乳癌的晚期與輔助治療中成功成為治療標靶。

# 在大腸直腸癌（CRC）中，HER2 基因擴增／過度表現相對罕見（整體約 3%），但在 RAS/BRAF 野生型腫瘤中發生率較高（報告為 5%–14%）。

有專門針對大腸直腸癌中 HER2 檢測的方法已被提出，HER2 標靶治療目前也已被建議作為 HER2 過度表現腫瘤患者後線治療選項。

(非預後因子)

# 針對 HER2 擴增 轉移性大腸直腸癌 (mCRC with HER2 amplifications)

四種不同的組套

作為 HER2 擴增的 轉移性大腸直腸癌 的可能後續治療的選擇。

(1). amtrastuzumab deruxtecan-nxki (T-DXd) monotherapy ( 優赫得 Enhertu fam-trastuzumab deruxtecan-nxki)

(2). trastuzumab in combination with pertuzumab (賀疾妥 PERJETA)

(3). trastuzumab in combination with lapatinib (泰嘉錠 TYKER)

(4). trastuzumab in combination with tucatinib (Tukysa ).

ps: Table from chatgpt

#

Regimen Mechanism Inclusion
Trastuzumab deruxtecan‑nxki (T‑DXd) (monotherapy) Antibody‑drug conjugate (ADC) (HER2‑targeted) DESTINY-CRC02

HER2-positive

(IHC 3+ or IHC 2+/ISH+) mCRC, with either RAS wild-type or mutant

disease

Trastuzumab + Pertuzumab # HER2 antibody

# Ab: inhibit the classical HER2-mediated cell-signaling cascades by blocking HER2 dimerization.

MyPathway (n=57)
Phase II basket study, TAPUR

Thirty-eight patients with CRC with ERBB2 amplification (N = 28) or ERBB2/3 mutations (N = 10)

Trastuzumab + Lapatinib # HER2 antibody

# inhibitor binding to ATP-binding pocket of the EGFR/HER2 protein kinase domain TKI)

HERACLES-A
Trastuzumab + Tucatinib # HER2 antibody

# Highly selective HER2‑targeted TKI

Phase II MOUNTAINEER ( n=117)

chemotherapy-refractory, HER2-positive, RAS wild-type unresectable or crc

Regimen Study ORR (%) PFS

(mo)

OS

(mo)

Notes
T‑DXd monotherapy DESTINY-CRC02 37.8%(5.4 mg/kg)

27.5%(6.4 mg/kg)

6.9 Notable ILD risk
Trastuzumab + Pertuzumab MyPathway (n=57) # 57 (all patients)

# 43 (HER2+, KRAS WT)

13 (HER2+, KRAS mutated)

32%

40%

8%

2.9

5.3

1.4

phase II basket study, TAPUR(n=28)

ERBB2 amplification

OR 25% 17.2 wks; 60 wks DCR 54%
Trastuzumab + Lapatinib HERACLES-A (n= 32) 28% 4.7m
Trastuzumab + Tucatinib Phase II MOUNTAINEER ( n=117) 38.1 8.5m

(post)

brain metastasis!!