Association of Tumor HER3 Expression With Treatment Outcome in Advanced Colorectal Cancer


Key Points

  • Among patients with wild-type RAS colorectal cancer, the addition of panitumumab to irinotecan was associated with better progression-free survival among those with high but not low HER3 expression.
  • Outcomes for overall survival were similar.

In a study reported in JAMA Oncology, Seligmann et al found that higher tumor HER3 messenger RNA expression among patients with RAS wild-type tumors was associated with a better outcome with panitumumab (Vectibix) plus irinotecan vs irinotecan alone among patients with advanced colorectal cancer in the UK phase III PICCOLO trial. The addition of panitumumab to irinotecan improved progression-free but not overall survival after failure on prior fluoropyrimidine treatment.

Outcomes According to HER3 Expression

In the prospectively planned biomarker study, higher HER3 expression as a continuous variable was prognostic for overall survival among all 308 patients (hazard ratio [HR] per twofold change = 0.91, P = .04) but not for progression-free survival (HR = 0.93, P = .25). Higher HER3 was associated with improved progression-free survival (HR = 0.71, P < .001) and overall survival (HR = 0.73, P <.001) among 115 patients with wild-type RAS who received panitumumab plus irinotecan but not among 94 patients receiving irinotecan alone (HR = 0.96, P = .65; HR = 0.93, P = .25). Interactions between biomarker and treatment were significant for both progression-free (P = .001) and overall survival (P = .004).

High vs Low Expression

In a binary model with high HER3 expression defined as that above the 66th percentile, median progression-free survival among wild-type RAS patients with high HER3 expression was 8.2 months with the combination vs 4.4 months with irinotecan alone (HR = 0.33, P < .001), whereas the median progression-free survival was 3.3 months vs 4.3 months among those with low HER3 expression (HR = 0.96, P = .84), with the interaction being significant (P = .002). In this analysis, the hazard ratio for overall survival for the combination vs irinotecan alone was 0.66 (P = .11) among patients with high expression and 1.56 (P = .02) among those with low expression, with a significant interaction (P = .01).

The investigators concluded: “High HER3 expression identified patients with RAS [wild-type] who gained markedly from panitumumab, and those who did not, with statistically significant biomarker-treatment interactions for [progression-free survival and overall survival]. This finding provides insight into the mechanism of anti-[epidermal growth factor receptor] agents and is of potential clinical utility.”

The study was supported by Cancer Research UK.

Matthew T. Seymour, MD, of the St. James Institute of Oncology, St. James’s University Hospital, Leeds, is the corresponding author of the JAMA Oncology article.

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