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第45卷第5期 卢蓉蓉，瞿 菲，李 薇. 抗体偶联药物用于乳腺癌治疗的耐药机制研究进展［J］.
2025年5月 南京医科大学学报（自然科学版），2025，45（5）：707-717 ·713 ·

表2 联合治疗相关临床研究
Table 2 Clinical trials related to combination therapy

Drugs
combined with Clinical trial Efficacy Safety
ADC
Chemotherapy Phase Ⅰb/Ⅱa（NCT00934856），T⁃DM1 The ORR in mBC patients（n=25） Neutropenia was the most common
drugs + docetaxel ± pertuzumab for HER2 ⁃ was 80.0%（20/25，95%CI：59.3%- grade 3- 4 AE（mBC，72% ；LABC，
positive LABC or mBC（n=98）：mBC 93.2%）；the mPFS is 13.8 months 29% ）.48%（12/25）of patients with
（n=25），LABC（n=73） （range 1.63-33.5 months） mBC and 47%（34/73）of patients with
The pCR rate in LABC patients（n= LABC experienced AE that required
73）was 60.3%（44/73，95% CI： dose adjustment
48.1%-71.5%）

PhaseⅠb/Ⅱa（NCT00951665），T⁃DM1 Among the 42 phase Ⅱ a patients 77.3% of patients experienced grade ≥
+ paclitaxel ± pertuzumab for HER2 ⁃ with measurable disease，the ORR 3 AE，the most common being neutro⁃
positive mBC：phase Ⅰb（n=104），was 50.0% （95% CI： 34.6%- penia（25.0%）and peripheral neuropa⁃
phase Ⅱa（n=60） 65.4% ）；CBR was 56.8%（95% thy（18.2%）
CI：41.6%-71.0%）
Targeted drugs Phase Ⅰb/Ⅱ DESTINY⁃Breast07 trial The ORR of T ⁃ DXd was 77.3% Nausea was the most common AE in
（NCT04538742），T⁃DXd±pertuzumab （80% CI：70.0%- 83.6% ）. The the T⁃DXd and T⁃DXd+ pertuzumab，
for HER2⁃positive mBC first⁃line thera⁃ ORR of T ⁃ DXd + pertuzumab was with incidence rates of 70.7% and
py ：T⁃DXd monotherapy（ n=75 ），T 82.0%（80%CI：73.1%-88.8%） 68.0%，res⁃pectively
⁃DXd+pertuzumab（n=50） The incidence of diarrhea was 34.7%
and 60.0%，respectively
Phase Ⅱ TEAL trial The proportion of patients with Common adverse events in the KLT
（NCT02073487），paclitaxel，trastu⁃ RCB 0 or 1 in the KLT and THP and THP groups included elevated liver
zumab，and pertuzumab（THP）and T⁃ groups was 100% vs. 62.5%，res ⁃ function（64.3% vs. 56.3%），diarrhea
DM1，lapatinib，and nab ⁃ paclitaxel pectively（P=0.003 5） （50.0% vs. 43.8%），and fatigue（42.9%
（KLT）；neoadjuvant therapy for HER2 In the ER ⁃ positive subgroup， vs. 50.0%）. There was no statistically
⁃positive breast cancer（n=30） 100% of patients in the KLT group significant difference in AE between
achieved RCB 0-1 compared to treatment groups
25% in the THP group（P=0.003
5）

Phase Ⅱ TBCRC 022 trial The CNS ORR in cohorts 4A，4B，Diarrhea was the most common grade 2
（NCT01494662），T ⁃ DM1 + neratinib and 4C was 33.3%（95%CI：4.3%- （31.8% ）and grade 3（22.7% ）AE；
for cohort 4A ⁃ previously untreated 77.7%），35.3%（95%CI：14.2%- grade 2 fatigue occurred in 12（27.3%）
BCBM，cohorts 4B and 4C⁃BCBM pro⁃ 61.7%），and 28.6%（95%CI：11.3%- patients
gressing after local CNS⁃directed ther⁃ 52.2%），respectively
apy without（4B）and with（4C）prior
exposure to T⁃DM1（n=44）：4A（n=6），
4B（n=17），4C（n=21）
Phase Ⅰb/Ⅱ NSABP FB ⁃ 10 trial In phase Ⅰb，the ORR was 12/19 Diarrhea was the most common grade 2
（NCT02236000），T⁃DM1 + neratinib （63%）. The ORR in phase Ⅱ was （27%）and grade 3（36%）AE. Other
for HER2 ⁃ positive metastatic breast 7/22（32%），and the CBR was 45% grade 3/4 toxicities included thrombo⁃
cancer patients who progressed on （10/22） cytopenia（10%），elevated aminotrans⁃
treatment with trastuzumab + pertuzu ⁃ ferase（15%）and pneumonia（5%）
mab（n=49）：Ⅰb（n=27）；Ⅱ（n=22）