Cetuximab beyond progression in Kras wild-type metastatic colorectal cancer

Abstract

Background: Cetuximab and bevacizumab have proven efficacy in the treatment of metastatic colorectal cancer (mCRC). Although new agents such as panitumumab, aflibercept and regorafenib emerge with modest clinical benefit, they are still not widely available. With limited options of target therapy, treatment with individual agent beyond progression is an attractive strategy and use of bevacizumab in this setting has been shown to improve survival. However, evidence for applying the same strategy to cetuximab is not clear. We performed a retrospective analysis to evaluate the clinical benefit of cetuximab beyond progression in Kras wild-type mCRC.

Methods: From January 2008 to December 2010, all patients referred to our department for further management of colorectal cancer were screened. Patients were eligible for further analysis if all the following criteria were met: [1] Kras wild-type mCRC, [2] received more than one line of systemic treatment, [3] no metastasectomy of curative intent performed, and [4] details of pre-referral treatment available. The primary end-point was median overall survival. Survival rate was estimated by the Kaplan-Meier method and predictors of outcomes were analyzed using Cox regression method. Statistical analysis was performed using SPSS.

Results: From January 2008 to December 2010, 732 patients were referred to our department for further management of colorectal cancer and 419 of them had either synchronous or metachronous metastatic disease. 55 patients met all the criteria for further analysis. The median age was 57 and 98% of them had good performance status (ECOG 0-1). 86% of patients presented with synchronous metastasis and 63% of patient had metastatic disease involving more than one organ. 31% of patients received more than 2 lines of systemic therapy (median: 2 cycles, range: 2-5 cycles). 75% of patients have been treated with all standard chemotherapeutic agents (oxaliplatin, irinotecan and fluoropyrimidine) while 42% of patients had exposure to both cetuximab and bevacizumab. The median follow-up was 20.1 months and 47 patients have died. The median overall survival was 21.2 months (95% CI: 20.4 – 27.1months). Using the Cox regression method, neither exposure to all standard chemotherapeutic agents nor exposure to all standard target therapies (cetuximab or bevacizumab) were significant predictors of outcomes on univariate analysis. Upon multivariate analysis, baseline platelet count >400 x 109/L (HR 2.35, 95% CI: 1.01-5.45, p = 0.047), metastasis involving more than one organ (HR 1.92, 95% CI: 1.01-3.66, p = 0.046) and cetuximab-based therapy given in at least 2 lines of treatment (HR 0.47, 95% CI: 0.24-0.90, p = 0.022) were significant predictors of survival.

Conclusion: In patients with Kras wild-type mCRC who are not candidate for metastasectomy of curative intent, the use of cetuximab beyond progression is associated with 53% lower risk of death (p = 0.022). Baseline patient characteristics including increased platelet count (p = 0.047) and metastasis involving more than one organ (p = 0.046) remain significant as predictors of inferior survival in this group of patients.