In an analysis reported in the Journal of Clinical Oncology, Germani et al identified the impact of HER2 status in patients with metastatic colorectal cancer (mCRC) receiving chemotherapy plus either bevacizumab or anti-EGFR agents.
Study Details
The study involved data from 1,604 patients with proficient mismatch repair (pMMR)/microsatellite stable (MSS) RAS/BRAF wild-type previously untreated mCRC with available HER2 amplification/expression status who received chemotherapy plus either bevacizumab or anti-EGFRs in eight randomized trials.
Key Findings
Compared with patients with HER2-negative disease, those with HER2-positive disease (n = 81; 5%) had shorter median progression-free survival (9.8 vs 12.2 months, hazard ratio [HR] = 1.31, P = .02) and overall survival (28.0 vs 34.9 months, HR = 1.37, P =.01), with the differences remaining significant (P = .02; P = .048) after adjustment for covariates.
No difference in objective response rate was observed between HER2-positive and HER2-negative tumors (75% vs 72%, odds ratio [OR] = 1.21, P = .47).
No significant interactions between HER2 amplification/expression status and the effects of bevacizumab vs anti-EGFRs were observed for progression-free survival (P for interaction = .76), overall survival (P for interaction = .76), or objective response rate (P for interaction = .64).
In left-sided HER2-positive tumors, outcomes were similar with chemotherapy plus bevacizumab vs anti-EGFRs for median progression-free survival (9.8 vs 9.3 months, HR = 0.73, P = .29), median overall survival (29.8 vs 28.0 months, HR = 1.29, P = .40), and objective response rate (59% vs 79%, OR = 0.39, P = .10).
Patients with HER2-mutant tumors (2% of patients with HER2-negative tumors) had shorter median overall survival vs patients with HER2 wild-type tumors (23.7 vs 34.4 months, HR = 1.56, P = .04) with no significant interaction observed for bevacizumab vs anti-EGFRs for objective response rate (P for interaction = .81), progression-free survival (P for interaction = .95), or overall survival (P for interaction = .92).
The investigators concluded: “To our knowledge, this is the largest analysis of HER2 status in patients with untreated mCRC enrolled in [randomized clinical trials]. Waiting for targeted approaches, [HER2-positive] and [mutant status] do not predict benefit from [bevacizumab/anti-EGFRs] and should be regarded as negative prognostic factors in pMMR/MSS RAS/BRAF wild-type mCRC.”
Chiara Cremolini, MD, PhD, of the Department of Translational Research and New Technologies in Medicine, University of Pisa, Pisa, Italy, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by Gruppo Oncologico del Nord Ovest Foundation, Arbeitsgemeinschaft Internistische Onkologie, and others. For full disclosures of all study authors, visit ascopubs.org.
