{"doi":"10.2147/dddt.s558378","title":"Pyrotinib Plus Trastuzumab as an Effective Later-Line Therapeutic Strategy for HER2-Positive Metastatic Colorectal Cancer: Results from a Phase II Study","abstract":"<h4>Background</h4>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.<h4>Methods</h4>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).<h4>Results</h4>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.<h4>Conclusion</h4>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.","journal":"Drug Design, Development and Therapy","year":2025,"id":12664,"datarank":0.10397207708399181,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"self_citation_contribution":0.10397207708399181,"citation_network_contribution":0.0,"self_endowment_contribution":0.10397207708399181,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.0415,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-11-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":13180,"name":"Jing Zhang","orcid":"0000-0002-5970-0509","position":1,"is_corresponding":false},{"id":98820,"name":"Guifu Wu","orcid":"0000-0002-2823-6643","position":2,"is_corresponding":false},{"id":50826,"name":"Wen Zhang","orcid":"0000-0001-7808-9867","position":3,"is_corresponding":false},{"id":98821,"name":"Aiping Zhou","orcid":null,"position":4,"is_corresponding":false},{"id":49086,"name":"Lin Yang","orcid":"0000-0003-0469-9288","position":5,"is_corresponding":false},{"id":98822,"name":"Yongkun Sun","orcid":"0000-0003-3302-6023","position":6,"is_corresponding":false},{"id":98819,"name":"Wenwei Yang","orcid":"0000-0002-7292-5980","position":0,"is_corresponding":true}],"reference_count":47,"raw_metadata":null,"created_at":"2026-03-01T18:20:47.508186Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}