Clinical outcome of panitumumab for metastatic colorectal cancer with wild-type KRAS status: a meta-analysis of randomized clinical trials

Abstract

Panitumumab is a fully human anti-epidermal growth factor receptor (EGFR) monoclonal antibody that has a favorable effect on patients with metastatic colorectal cancer (mCRC) harboring wild-type (WT) KRAS gene. This meta-analysis was planned to quantify the benefit and assess safety. Selected for the analysis were randomized clinical studies that have used panitumumab-based therapy (PBT) for patients with mCRC and where the outcome of patients with WT KRAS was reported. Four eligible studies were analyzed including 1,010 and 1,105 patients who received PBT and the control intervention, respectively. Used in subsequent-line setting, PBT was associated with 42% improvement in progression-free survival (PFS) (hazard ratio [HR] = 0.58; 95% CI, 0.36-0.93; P = 0.02), a non-significant overall survival (OS) benefit (HR = 0.90; [95% CI, 0.76-1.05]; P = 0.18), and a significant increase in objective response rate (ORR) (odds ratio (OR) = 0.67 [95% CI, 1.15-77.98]; P = 0.04). PBT showed no benefit in the first-line setting. Restricted analysis to two studies (first- and second-line setting), where the treatment effect of PBT was prospectively analyzed according to tumor KRAS status, showed significant PFS (HR = 0.77), OS (HR = 0.84), and ORR (OR = 2.06) advantage. Almost all patients' subgroups attained clinical benefit. PBT-related adverse events were similar across comparisons with the exception of toxicities known to be associated with anti-EGFR therapy. This meta-analysis showed significant clinical benefit for PBT for patients with WT KRAS mCRC predominantly when used following prior chemotherapy exposure. The benefit was demonstrated in most subgroup analyses. Further research to better define potential responders is needed.

Current targeted therapies in the treatment of advanced colorectal cancer: a review

“…A meta-analysis in 2011 of four randomized clinical studies found significant clinical benefit for panitumumab-based therapy in wild-type KRAS mCRC patients following prior chemotherapy exposure [Ibrahim and Abouelkhair, 2011].…”

BRAF Mutations as Predictive Biomarker for Response to Anti-EGFR Monoclonal Antibodies

“…As supportive evidence for KRAS exons 2, 3, and 4 testing, ASCO referred to ten meta‐analyses and two health technology assessment reports that reviewed 137 primary studies with 19,543 patients. Table summarizes findings of these ten meta‐analyses.…”

“…This is mainly due to lack of consistent OS benefit when adding anti‐EGFR mAbs to standard of care in the overall and KRAS wt population. In KRAS wt patients, OS benefit was detected in only 6 out of 13 trials .…”

Targeted Therapies in Metastatic Colorectal Cancer: A Systematic Review and Assessment of Currently Available Data

“…For panitumumab, one meta-analysis was assessed [36]. All patients included in the analysis had KRAS WT tumor status.…”