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已发表论文
吡咯替尼联合曲妥珠单抗作为 HER2 阳性转移性结直肠癌后线治疗的有效策略：一项 II 期研究结果
Authors Yang W , Zhang J, Wu G, Zhang W, Zhou A, Yang L, Sun Y
Received 5 August 2025
Accepted for publication 14 November 2025
Published 21 November 2025 Volume 2025:19 Pages 10269—10280
DOI https://doi.org/10.2147/DDDT.S558378
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Professor Manfred Ogris
Wenwei Yang,1,* Jing Zhang,1,* Guifu Wu,2,* Wen Zhang,1 Aiping Zhou,1 Lin Yang,1 Yongkun Sun1
1Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, People’s Republic of China; 2Department of Medical Oncology, Beijing Chaoyang District Sanhuan Cancer Hospital, Beijing, 100122, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Yongkun Sun, Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Chaoyang District Panjiayuan Nanli No. 17, Beijing, 100021, People’s Republic of China, Email hsunyk@cicams.ac.cn Lin Yang, Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Chaoyang District Panjiayuan Nanli No. 17, Beijing, 100021, People’s Republic of China, Email linyangcicams@126.com
Background: Dual human epidermal growth factor receptor 2 (HER2) blockade demonstrates promising yet limited clinical activity in HER2-positive metastatic colorectal cancer (mCRC). This study was initiated to evaluate the novel combination of trastuzumab (anti-HER2 monoclonal antibody) and pyrotinib (a pan-HER tyrosine kinase inhibitor) in this molecularly defined population.
Methods: This exploratory single-arm phase II trial enrolled HER2-positive mCRC patients refractory to standard first- and second-line therapies. Participants received intravenous trastuzumab (8 mg/kg loading dose on cycle 1 day 1, then 6 mg/kg every 3 weeks) plus oral pyrotinib 400 mg once daily in 21-day cycles. The primary endpoint was objective response rate (ORR).
Results: Between December 1, 2019, and March 31, 2025, 20 patients were enrolled, with 17 evaluable for efficacy. The objective response rate (ORR) was 23.5% (4 partial responses), and the disease control rate (DCR) reached 88.2%. Median progression-free survival (PFS) was 6.2 months (95% CI, 0.42– 11.98), and median overall survival (OS) was 21.1 months (95% CI, 15.84– 26.36). Responses occurred exclusively in RAS/BRAF wild-type patients (ORR 28.6%; DCR 92.9%), who showed significantly longer median PFS (8.5 vs 2.6 months; HR 0.32; P=0.008) and OS (22.6 vs 4.9 months; P=0.022) versus KRAS-mutant counterparts. Treatment-related adverse events (TRAEs) included diarrhea (75%), fatigue (40%), and nausea (35%). Diarrhea accounted for all grade 3 TRAEs (30%). No grade ≥ 4 TRAEs were observed.
Conclusion: Pyrotinib plus trastuzumab demonstrates clinically meaningful efficacy and a manageable safety profile in heavily pretreated HER2-positive metastatic colorectal cancer. These findings support advancing this regimen as a potential alternative in refractory HER2-positive mCRC, particularly in the RAS/BRAF wild-type subgroup.
Plain Language Summary: This phase II trial explored the novel dual HER2 blockade of oral pyrotinib plus trastuzumab in heavily pretreated HER2-positive metastatic colorectal cancer (mCRC). The regimen demonstrated clinically meaningful efficacy (ORR 23.5%, DCR 88.2%, median PFS 6.2 mo, OS 21.1 mo) with a manageable safety profile dominated by low-grade diarrhea. Crucially, all responses occurred in RAS/BRAF wild-type tumors, where outcomes were significantly superior (ORR 28.6%, PFS 8.5 mo, OS 22.6 mo) versus KRAS-mutant patients. These findings support advancing this regimen as a potential alternative in refractory HER2-positive mCRC, particularly in the RAS/BRAF wild-type subgroup.
Keywords: metastatic colorectal cancer, trastuzumab, pyrotinib, HER2, target therapy
1Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, People’s Republic of China; 2Department of Medical Oncology, Beijing Chaoyang District Sanhuan Cancer Hospital, Beijing, 100122, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Yongkun Sun, Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Chaoyang District Panjiayuan Nanli No. 17, Beijing, 100021, People’s Republic of China, Email hsunyk@cicams.ac.cn Lin Yang, Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Chaoyang District Panjiayuan Nanli No. 17, Beijing, 100021, People’s Republic of China, Email linyangcicams@126.com
Background: Dual human epidermal growth factor receptor 2 (HER2) blockade demonstrates promising yet limited clinical activity in HER2-positive metastatic colorectal cancer (mCRC). This study was initiated to evaluate the novel combination of trastuzumab (anti-HER2 monoclonal antibody) and pyrotinib (a pan-HER tyrosine kinase inhibitor) in this molecularly defined population.
Methods: This exploratory single-arm phase II trial enrolled HER2-positive mCRC patients refractory to standard first- and second-line therapies. Participants received intravenous trastuzumab (8 mg/kg loading dose on cycle 1 day 1, then 6 mg/kg every 3 weeks) plus oral pyrotinib 400 mg once daily in 21-day cycles. The primary endpoint was objective response rate (ORR).
Results: Between December 1, 2019, and March 31, 2025, 20 patients were enrolled, with 17 evaluable for efficacy. The objective response rate (ORR) was 23.5% (4 partial responses), and the disease control rate (DCR) reached 88.2%. Median progression-free survival (PFS) was 6.2 months (95% CI, 0.42– 11.98), and median overall survival (OS) was 21.1 months (95% CI, 15.84– 26.36). Responses occurred exclusively in RAS/BRAF wild-type patients (ORR 28.6%; DCR 92.9%), who showed significantly longer median PFS (8.5 vs 2.6 months; HR 0.32; P=0.008) and OS (22.6 vs 4.9 months; P=0.022) versus KRAS-mutant counterparts. Treatment-related adverse events (TRAEs) included diarrhea (75%), fatigue (40%), and nausea (35%). Diarrhea accounted for all grade 3 TRAEs (30%). No grade ≥ 4 TRAEs were observed.
Conclusion: Pyrotinib plus trastuzumab demonstrates clinically meaningful efficacy and a manageable safety profile in heavily pretreated HER2-positive metastatic colorectal cancer. These findings support advancing this regimen as a potential alternative in refractory HER2-positive mCRC, particularly in the RAS/BRAF wild-type subgroup.
Plain Language Summary: This phase II trial explored the novel dual HER2 blockade of oral pyrotinib plus trastuzumab in heavily pretreated HER2-positive metastatic colorectal cancer (mCRC). The regimen demonstrated clinically meaningful efficacy (ORR 23.5%, DCR 88.2%, median PFS 6.2 mo, OS 21.1 mo) with a manageable safety profile dominated by low-grade diarrhea. Crucially, all responses occurred in RAS/BRAF wild-type tumors, where outcomes were significantly superior (ORR 28.6%, PFS 8.5 mo, OS 22.6 mo) versus KRAS-mutant patients. These findings support advancing this regimen as a potential alternative in refractory HER2-positive mCRC, particularly in the RAS/BRAF wild-type subgroup.
Keywords: metastatic colorectal cancer, trastuzumab, pyrotinib, HER2, target therapy