Impact of Human Epidermal Growth Factor Receptor 2 in Patients With Metastatic Colorectal Cancer Treated With Chemotherapy Plus Bevacizumab or Anti-EGFRs: Exploratory Analysis of Eight Randomized Trials.

As compared with HER2 wild-type tumors, HER2 mut showed similar ORR (63% v 72%, OR, 0.67 [95% CI, 0.31 to 1.55]; P = .33), numerically shorter PFS (median: 9.4 v 12.1 months, HR, 1.36 [95% CI, 0.90 to 2.06]; P = .14), and significantly shorter OS (median: 23.7 v 34.4 months, HR, 1.56 [95% CI, 1.02 to 2.38]; P = .04; Figs 4 A- 4 C), reaching marginal significance in multivariate analysis after adjustment for covariates (HR, 1.53 [95% CI, 0.98 to 2.38]; P = .059).

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Assuming that activating HER2 mutations elicit a downstream biological effect resembling that of HER2-pos, 1 , 2 , 18 our findings, showing their negative prognostic impact among patients with pMMR/MSS HER2-neg RAS/BRAF wild-type tumors, with a borderline significant result also after adjustment for covariates, are not surprising though certainly novel.

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