HER-2 positive + RAS wild-type

P2, N=37, Recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Dec 2025 --> Dec 2026 | Trial primary completion date: Dec 2025 --> Dec 2026

P2, N=90, Not yet recruiting, The First Affiliated Hospital of Henan University of Chinese Medicine; The First Affiliated Hospital of Henan University of Chinese Medicine

P=N/A, N=105, Recruiting, AstraZeneca | N=384 --> 105

Dual HER2-targeted therapy combined with chemotherapy is a promising strategy for HER2-positive mCRC patients with good performance status. This approach warrants validation in large-scale clinical trials to confirm its efficacy.

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.

To our knowledge, this is the largest analysis of HER2 status in patients with untreated mCRC enrolled in RCT. Waiting for targeted approaches, HER2-pos and mut do not predict benefit from bev/anti-EGFRs and should be regarded as negative prognostic factors in pMMR/MSS RAS/BRAF wild-type mCRC.

P2, N=25, Active, not recruiting, University of Wisconsin, Madison | Recruiting --> Active, not recruiting

Multiple HER2-targeted regimens are now part of National Comprehensive Cancer Network and European Society for Medical Oncology guidelines with two recent Food and Drug Administration approvals for previously treated HER2-positive metastatic colorectal cancer for tucatinib (in combination with trastuzumab) and for trastuzumab-deruxtecan in patients with previously treated HER2-positive metastatic colorectal cancer. This review explores the prognostic and predictive value of HER2 as a biomarker in CRC, describing its molecular structure, the clinical characteristics of patients with HER2 alterations, diagnostic approaches and the most relevant clinical trials assessing its current and future role as a therapeutic target in metastatic colorectal cancer.

P2, N=24, Not yet recruiting, Peking Union Medical College Hospital; Peking Union Medical College Hospital

As the landscape of HER2-directed therapies continues to evolve, these findings suggest that ERBB2 alterations and HER2 expression may represent a potential therapeutic target in LGSC.

It is also associated with resistance against epidermal growth factor receptor (EGFR)-targeted therapies like cetuximab and panitumumab, for treatment of RAS wild-type mCRC. Furthermore, anti-HER2 therapies exhibited non-toxic profile and high efficacy in chemorefractory cases. This review delves into modern management of anti-HER2 therapies in CRC with a particular focus on recent advances and current knowledge about the prognostic and predictive value of HER2.

P2, N=112, Recruiting, Gruppo Oncologico del Nord-Ovest | Trial primary completion date: May 2025 --> May 2026