Clinical impact of anti-epidermal growth factor receptor monoclonal antibodies in first-line treatment of metastatic colorectal cancer. Meta-analytical estimation and implications for therapeutic strategies

BACKGROUND: Antiepidermal growth factor receptor (anti-EGFR) monoclonal antibodies (MoAbs) are indicated for the treatment of metastatic colorectal cancer patients, but some scientific issues concerning their efficacy are currently unsolved. METHODS: A literature-based meta-analysis was conducted. Hazard ratios (HRs) were extracted from randomized trials for progression-free survival (PFS) and overall survival (OS); the event-based risk ratio was derived for response. Sensitivity analyses to look for interactions according to KRAS status and chemotherapy association regimens were performed. RESULTS: Eight trials (6609 patients) were identified. A significant interaction according to KRAS status was found for PFS (wild type vs mutant, P =.001) and response rate (wild type vs mutant, P <.0001). The addition of an anti-EGFR MoAb to first-line chemotherapy increased PFS in the KRAS wild-type population (HR, 0.91; 95% confidence interval [CI], 0.84-0.99; P =.03), and had a detrimental effect in the KRAS mutant population (HR, 1.13; 95% CI, 1.03-1.25; P =.013). A significant increase in the probability of achieving a response was evident in KRAS wild-type patients (relative risk, 1.17; 95% CI, 1.04-1.33; P =.011). In this population, the interaction in response rate according to adopted chemotherapy favored irinotecan-containing regimens (P =.01), and at meta-regression analysis the relative increase in response rate was significantly related to PFS (P =.00001) and OS (P =.00193) benefit. CONCLUSIONS: The addition of an anti-EGFR MoAb to first-line chemotherapy produces a clear benefit in response rate. This advantage is restricted to KRAS wild-type patients and translates into a small benefit in PFS. At present, irinotecan-based backbone chemotherapy could be a preferable option. The correlation between activity and survival parameters corroborates the hypothesis that anti-EGFR MoAbs might be more suitable for patients needing tumoral shrinkage.