A recent study examined the association between colorectal cancer messenger RNA (mRNA) expression of HER3 with response to anti-EGFR agents, published in JAMA Oncology (online October 26, 2017; doi:10.1001/jamaoncol.2017.3168).
A previous trial showed that high EGFR ligand expression is predictive of panitumumab efficacy in advanced colorectal cancer. A better understanding of tumor expression of HER3 may help refine the RAS wild-type subtype benefiting from anti-EGFR agents such as panitumumab.
Jenny F Seligmann, PhD, Leeds Institute of Cancer and Pathology, University of Leeds (England), and colleagues conducted a study to examine HER3 mRNA expression as a potential prognostic biomarker for anti-EGFR therapy in advanced RAS wild-type colorectal cancer. The prospective, randomized trial sampled 308 patients given panitumumab. HER3 was first assessed as a prognostic marker, then as a predictive biomarker in patients with RAS wild-type.
The primary endpoint was progression-free survival (PFS) and the secondary endpoints were response rate and overall survival (OS).
Results of the study showed that higher HER3 expression was only slightly prognostic for OS (HR per 2-fold change, 0.91; 95% CI, 0.83-0.99; P = .04) and not at all prognostic for PFS (HR, 0.93; 95%CI, 0.83-1.05; P = .25). On the contrary, higher HER3 expression was predictive of prolonged PFS for patients receiving panitumumab plus irinotecan (HR, 0.71; 95% CI, 0.61-0.82; P < .001), but not irinotecan alone (HR, 0.96; 95% CI, 0.82-1.13; P = .65) in patients with RAS wild-type disease. A similar interaction was observed for OS (P = .004).
Additionally, researchers conducted an exploratory binary model and found that HER3 was predictive of panitumumab benefit; in patients with high HER3 expression, median PFS was 8.2 months vs 4.4 months for those receiving the combination therapy compared with those receiving irinotecan alone, respectively. The binary model also showed predictive benefit for OS, with significant interaction (P = .01).
Authors of the study concluded that high HER3 expression helps identify patients with RAS wild-type advanced colorectal cancer who benefit from anti-EGFR therapy. “This finding provides insight into the mechanism of anti-EGFR agents and is of potential clinical utility,” they wrote.—Zachary Bessette