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.
BACKGROUND: Antiepidermal growth factor receptor (anti-EGFR) monoclonal antibodies (MoAbs) are indicated for the treatment of metastatic colorectal cancerpatients, 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.
Authors: Antonia R Sepulveda; Stanley R Hamilton; Carmen J Allegra; Wayne Grody; Allison M Cushman-Vokoun; William K Funkhouser; Scott E Kopetz; Christopher Lieu; Noralane M Lindor; Bruce D Minsky; Federico A Monzon; Daniel J Sargent; Veena M Singh; Joseph Willis; Jennifer Clark; Carol Colasacco; R Bryan Rumble; Robyn Temple-Smolkin; Christina B Ventura; Jan A Nowak Journal: J Mol Diagn Date: 2017-02-06 Impact factor: 5.568
Authors: Antonia R Sepulveda; Stanley R Hamilton; Carmen J Allegra; Wayne Grody; Allison M Cushman-Vokoun; William K Funkhouser; Scott E Kopetz; Christopher Lieu; Noralane M Lindor; Bruce D Minsky; Federico A Monzon; Daniel J Sargent; Veena M Singh; Joseph Willis; Jennifer Clark; Carol Colasacco; R Bryan Rumble; Robyn Temple-Smolkin; Christina B Ventura; Jan A Nowak Journal: Am J Clin Pathol Date: 2017-02-03 Impact factor: 2.493
Authors: David L Chan; Nick Pavlakis; Jeremy Shapiro; Timothy J Price; Christos S Karapetis; Niall C Tebbutt; Eva Segelov Journal: PLoS One Date: 2015-08-14 Impact factor: 3.240