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Clinical impact of anti‐epidermal growth factor receptor monoclonal antibodies in first‐line treatment of metastatic colorectal cancer
Author(s) -
Loupakis Fotios,
Cremolini Chiara,
Salvatore Lisa,
Schirripa Marta,
Lonardi Sara,
Vaccaro Vanja,
Cuppone Federica,
Giannarelli Diana,
Zagonel Vittorina,
Cognetti Francesco,
Tortora Giampaolo,
Falcone Alfredo,
Bria Emilio
Publication year - 2011
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.26460
Subject(s) - medicine , kras , cetuximab , oncology , hazard ratio , irinotecan , colorectal cancer , population , chemotherapy , epidermal growth factor receptor , panitumumab , confidence interval , cancer , environmental health
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. Cancer 2011;. © 2011 American Cancer Society.