FIRST-LINE CHEMOTHERAPY PLUS CETUXIMAB IN PATIENTS GROUPED ACCORDING TO PROGNOSTIC RISK FACTORS: ANALYSIS OF THE CRYSTAL AND OPUS STUDIES

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Abstract

Background

Analysis of randomized trials has shown that mCRC patients can be divided into prognostic risk groups according to baseline clinical parameters including ECOG performance status, white blood cell count (WBC), alkaline phosphatase (ALP) and number of metastatic (met) sites (Köhne C, et al. Ann Oncol 2002; 13: 308–317). The effect of adding cetuximab to first-line chemotherapy (CT) on overall survival (OS) in these groups of KRAS wild-type mCRC patients was investigated in the CRYSTAL and OPUS studies.

Methods

Patient risk groups were: low-risk (LRG= ECOG 0/1, 1 met site), intermediate-risk (IRG= ECOG <1, >1 met site, ALP <300 U/l or, ECOG > 1, low WBC, 1 met site) and high-risk (HRG = ECOG < 1, >1 met site, ALP > 300 U/L or ECOG > 1, high WBC, or ECOG > 1, low WBC and >2 met sites). Exploratory analyses comprised estimates of effects using Cox's proportional hazards model for OS on individual patient data and comparison of treatment arms by log-rank test.

Results

In the pooled analyses, in both treatment arms, OS was longest in LRG patients (median 27.0 months, 95% CI 24.8–29.5 for the CT + cetuximab group [n = 173] and 25.7 months, 95% CI 21.9–8.7 for the CT group [n = 164]), and shortest in HRG patients (median 17.7 months, 95% CI 13.1–19.3 for the CT + cetuximab group [n = 46]; 12.6 months, 95% CI 9.2–14.4 for the CT group [n = 59]). In IRG patients median OS was 16.4 (95% CI 14.9–20.0) and 22.2 months (95% CI 19.5–25.7) in the CT (n = 213) and CT + cetuximab (n = 166) arms, respectively. Adding cetuximab to CT led to marked improvements in OS in the HRG (hazard ratio [HR] 0.765, 95% CI 0.506–1.157, P = 0.203) and IRG (HR 0.781, 95% CI 0.622–0.981, P = 0.033), while improvements in LRG patients (HR 0.869, 95% CI 0.672–1.124, P = 0.287) were observed only after prolonged follow-up. Data were similar in the separate CRYSTAL and OPUS studies.

Conclusions

The analysis confirms the concept of prognostic risk groups for OS according to baseline clinical parameters in patients with KRAS wild-type mCRC. Benefit from the addition of cetuximab to first-line CT in terms of OS appears to be more pronounced in the IRG and HRG.

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