Overall survival of patients with KRAS wild-type tumor treated with FOLFOX/FORFIRI±cetuximab as the first-line treatment for metastatic colorectal cancer: A meta-analysis

Abstract

The addition of cetuximab to FOLFIRI or FOLFOX as the first-line treatment for metastatic colorectal cancer (mCRC) was shown to reduce the risk of disease progression and increase the chance of response in patients with KRAS wild-type disease. An updated systematic meta-analysis was undertaken to determine the efficacy of cetuximab plus FOLFIRI or FOLFOX.Major databases were searched to identify RCTs investigating wild-type KRAS mCRC after the first-line treatment, and treatment with FOLFOX/FORFIRI ± cetuximab was compared. Data on clinical efficacy and safety were pooled and compared by ORs, HRs, and 95% CIs.Five eligible trials with 1464 patients were included in the meta-analysis. Compared to FOLFOX/FORFIRI, cetuximab as the first-line therapy has improved overall survival (OS) (hazard ratio [HR] = 0.82, 95% confidence interval [CI]: 0.72-0.93, P = 0.003), progression-free survival (PFS) (HR = 0.66, 95% CI: 0.56 -0.77, P < 0.00001), and overall response rate (ORR) (odds ratio [OR] = 2.12, 95% CI: 1.70-2.65, P < 0.00001). However, Grade 3/4 AE was increased with the OR of 2.76 (95%CI: 2.01-3.78, P < 0.00001). The most common grade 3/4 toxicity in the wild-type KRAS population was neutropenia and diarrhea. For cetuximab plus FOLFIRI, there was a higher incidence of grade 3 or 4 diarrhea (OR = 1.76, 95% CI: 1.15-2.70, P = 0.01), but there was no significant difference for neutropenia (OR = 1.35, 95% CI: 1.00-1.83, P = 0.05).The addition of cetuximab in mCRC as the first-line treatment is a potential effective approach in the improved outcomes but associated with increased toxicity.

Figure 1

Flow chart of selection.

Figure 2

Forest plot for OS. Meta-analysis of overall survival associated with cetuximab plus FOLFIRI or FOLFOX versus FOLFIRI or FOLFOX alone in the fixed-effects model. OS = overall survival.

Figure 3

Forest plot for PFS. Meta-analysis of progression-free survival between cetuximab plus FOLFIRI or FOLFOX and FOLFIRI or FOLFOX alone. PFS = progression-free survival.

Figure 4

Forest plot for ORR. Meta-analysis of overall response rate associated with cetuximab plus FOLFIRI or FOLFOX versus FOLFIRI or FOLFOX alone in the fixed-effects model. ORR = overall response rate.

Figure 5

Forest plot for Grade 3/4 toxicity. Meta-analysis of Grade 3/4 toxicity on cetuximab plus FOLFIRI or FOLFOX versus FOLFIRI or FOLFOX alone.

Figure 6

Funnel plot for the publication bias tests. (A) Funnel plot for the HR of OS; (B) funnel plot for the HR of FPS; (C) funnel plot for the OR of ORR. Each point represents a separate study for the indicated association. HR = hazard ratio, ORR = overall response rate, OS = overall survival, FPS = progression-free survival.