Many patients with HER2-positive, metastatic colorectal cancer (CRC) do not receive HER2-targeted therapy as recommended by National Comprehensive Cancer Network (NCCN) guidelines, according to a study published in the Journal of the National Comprehensive Cancer Network.

In this retrospective study, researchers examined data from 142 patients who were diagnosed with HER2-positive metastatic CRC between 2014 and 2020. Most patients (n=79) were diagnosed prior to 2018.

Nearly a quarter of patients (22.5%) had ERBB2 mutations as well as ERBB2 amplification. Patients also had mutations in KRAS (23.9%), PIK3CA (21.8%), MET (8.5%), NRAS (3.5%), and BRAF (2.1%). Of the 39 patients with available microsatellite instability (MSI) data, none had MSI-high tumors.

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The most common treatment prior to 2018 was anti-VEGF therapy, with or without chemotherapy, which was prescribed to 31.6% of patients. After 2018, the most common regimen was HER2-directed therapy, with or without chemotherapy, which was prescribed to 36.5% of patients.

The use of HER2-directed therapy increased from 22.8% before 2018 to 36.5% after. The use of anti-VEGF therapy, with or without chemotherapy, declined from 31.6% to 30.2%. The use of chemotherapy alone decreased from 21.5% to 19.0%.

The use of anti-EGFR therapy, with or without chemotherapy, decreased from 12.7% before 2018 to 6.3% after. The use of trifluridine plus tipiracil or regorafenib remained the same, at 6.3%. The use of other non-NCCN recommended regimens decreased from 5.1% to 1.6%.

The median time to next treatment was longer among patients treated with HER2-directed therapy than among those treated with other agents —11.0 months and 7.2 months, respectively.

“This real-world study … showed that many patients do not receive HER2-directed therapy despite its inclusion in NCCN guidelines, with heterogeneous treatment patterns suggesting that standard of care remains undefined and targeted therapy remains underutilized,” the researchers wrote. “Greater awareness of the unmet need in this patient population, together with new effective therapies, will facilitate strategies for improved, targeted treatment approaches.”

Disclosures: This study was supported by Seagen Inc. in collaboration with Merck Sharp & Dohme Corp. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


Strickler JH, Hsu L-I, Wright P, et al. Real-world treatment patterns in patients with HER2-amplified metastatic colorectal cancer: A clinical-genomic database study. J Natl Compr Canc Netw. 2023;21(8):805-812.e1. doi:10.6004/jnccn.2023.7022