Prognostic and Treatment-Specific Predictive Implications of HER2 Expression in RAS Wild-Type Metastatic Colorectal Cancer: A Multicenter Retrospective Real-World Study
Year: 2026
Type: article
Study design: Observational Study
Abstract: Background: Human epidermal growth factor receptor 2 (HER2) alterations have been implicated as mechanisms of resistance to anti-epidermal growth factor receptor (anti-EGFR) therapy in metastatic colorectal cancer (mCRC). We aimed to evaluate the predictive and prognostic significance of HER2 expression in patients with RAS wild-type mCRC in a real-world setting. Methods: We conducted a multicenter retrospective cohort study across ten oncology centers in Turkey, including patients with RAS wild-type mCRC treated between 2015 and 2022. Clinical outcomes, including progression-free survival (PFS) and overall survival (OS), were compared between HER2-positive and HER2-negative groups. Multivariable Cox proportional hazards models were used to identify independent predictors of survival outcomes. Results: Among 204 patients, 28 (13.7%) were HER2-positive. Baseline characteristics were generally comparable; however, HER2-positive patients showed a trend toward higher-grade tumors and were significantly less likely to receive anti-EGFR therapy. HER2-positive patients had significantly shorter PFS compared to HER2-negative patients (median 10 vs. 13 months; p = 0.006). In multivariable analysis, HER2 positivity remained an independent predictor of shorter PFS (HR 1.76, 95% CI 1.01–3.07; p = 0.045). In the subgroup of 144 patients receiving anti-EGFR therapy, HER2-positive patients also demonstrated significantly shorter PFS (median 9.0 vs. 14.0 months; p = 0.023). No significant differences in OS were observed between groups. Conclusions: HER2 positivity is associated with reduced response to anti-EGFR therapy and independently predicts shorter PFS in patients with RAS wild-type mCRC. These findings further support the role of HER2 as a clinically relevant biomarker in RAS wild-type mCRC, particularly in predicting response to anti-EGFR therapy, while highlighting the need for optimized patient selection strategies in the era of HER2-targeted treatments.
Source: Journal of Clinical Medicine
DOI: 10.3390/jcm15103979
Authors: Özlem Özdemir, Damla Günenç, Halil Taşkaynatan, Pınar Peker, Emir Gökhan Kahraman, Sedat Biter, Semra Paydaş, Tuğba Önder, Öztürk Ateş, Muhammed Muhiddin Er, Murat Araz, Ahmet Melih Arslan, Hüseyin Salih Semiz, Nilüfer Avcı, İzzet Doğan, Akif Doğan, Teoman Şakalar, Timur Köse, Asuman Argon, Enver İlhan, Başak Doğanavşargil Yakut, Murat Sezak, Bülent Karabulut
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,137
OpenAlex ID: W7162028678