Correlation of cetuximab-induced skin rash and outcomes of solid tumor patients treated with cetuximab: A systematic review and meta-analysis

https://doi.org/10.1016/j.critrevonc.2014.07.005Get rights and content

Highlights

  • This is a meta-analysis of the cetuximab-induced rash and outcomes of solid tumor patients.

  • A total of 13 clinical trials were considered eligible for the meta-analysis.

  • It demonstrated that cetuximab-induced rash is associated with an improved OS.

Abstract

Background

We performed a systematic review and meta-analysis of the correlation between cetuximab-induced skin rash and outcomes of solid tumor patients treated with cetuximab.

Patients and methods

Eligible studies included phase I, II and III trials of patients with solid tumors on cetuximab; describing events of skin rash and correlating skin rash with overall survival (OS), progression free survival (PFS) and/or overall response rate (ORR).

Results

Our search strategy yielded 409 potentially relevant citations on CETUXIMAB from Pubmed/Medline, CENTRAL Cochrane registry and ASCO meeting library. After exclusion of ineligible studies, a total of 13 clinical trials were considered eligible for the meta-analysis, including 4 phase III trials, 8 phase II trials and one phase I trial. The occurrence of cetuximab-induced rash in patients was highly associated with improvements in PFS (HR = 0.74; 95% CI: 0.63–0.86, P < 0.0002), OS (HR = 0.60; 95% CI: 0.47–0.76, P < 0.0001), and ORR (RR = 1.51, 95% CI: 1.26–1.81, P < 0.00001), as compared to patients without rash. Exploratory subgroup analysis showed no effect of tumor types on the RR of ORR.

Conclusions

Our meta-analysis has demonstrated that cetuximab-induced rash is associated with a significantly improved OS, PFS and ORR. Cetuximab-induced skin rash may represent a prognostic factor in patients with advanced solid tumors.

Introduction

The epidermal growth factor (EGF) signaling pathway is an interesting newly discovered target for cancer therapy. A recombinant humanized monoclonal antibody against epidermal growth factor Receptor (EGFR), cetuximab, has been developed to treat many solid tumors [1], [2].

Currently, the United States Food and Drug Administration (FDA) has approved cetuximab for patients metastatic colorectal carcinoma, non-small cell lung cancer and head and neck squamous cell carcinoma [3], [4], [5].

These agents have been accompanied by a unique spectrum of adverse events, which are different from traditional cytotoxic anticancer therapies. This includes skin toxicities, infusion reactions, hypomagnesemia and hypokalemia [6], [7].

As mentioned above, skin rash is a common side effect of cetuximab treatment usually easily managed by standard topical and/or systemic therapies. Interestingly, many clinical trials have found that patients with solid tumors treated with cetuximab who developed skin rash had a better prognosis than those without skin rash. However, there has been no systematic attempt to synthesize the data; and the correlation between skin rash induced by cetuximab and outcome measures like overall survival, progression free survival and overall response rate has yet to be defined. Therefore, we conducted a systematic review and meta-analysis of available clinical trials to determine such correlation.

Section snippets

Data sources

The study was performed using a pre-specified search strategy with pre-defined eligibility criteria. We did a comprehensive search of PubMed, CENTRAL Cochrane database and Google Scholar to retrieve relevant studies that reported the predictive value of skin rash regarding response and/or progression and/or survival in solid tumor patients treated with cetuximab. The search end date was January 2014, with no specified start date. Search term combinations were “cetuximab”, and “skin rash” in all

Search results

Our search strategy yielded 409 potentially relevant citations on CETUXIMAB from Pubmed/Medline, CENTRAL Cochrane registry and ASCO meeting library. The reasons for study exclusion are shown in Fig. 1. Thus, a total of 13 clinical trials were considered eligible for the meta-analysis, including 4 phase III trials, 8 phase II trials and one phase I trial. Cetuximab was used as a monotherapy in 3 trials while it was combined with radiotherapy in one trial and with other systemic agents in 9

Discussion

To the best of our knowledge, this is the first meta-analysis to provide a comprehensive evaluation of the Correlation of cetuximab-induced skin rash and outcomes of solid tumor patients treated with cetuximab. Our analysis of data from multiple studies demonstrated a significantly improved OS, PFS and ORR for patients with skin rash with compared with control.

Our exploratory subgroup analysis showed no effect of tumor types on the RR of ORR.

Proliferation and mitogenic potential of cancer

Role of funding source

This study was not funded by any sponsors.

Conflicts of interest statement

The authors declare that they have no conflicts of interest.

Author's contributions

OA provided the idea and study design and collected the data and wrote the manuscript. MF collected the data and revised the manuscript.

Reviewers

Uwe Wollina, Academic Teaching Hospital, Friedrichstrasse 41, Dresden-Friedrichstadt, D-01067 Dresden, Germany.

Jianming Xu, Chinese PLA Postgraduate Medical School, Beijing 100853, China.

Omar Abdel-Rahman graduated from Faculty of Medicine, Ain Shams University on December 2005, obtained Master degree in Clinical Oncology since 2009, he is working currently as an assistant lecturer of Clinical Oncology, Ain Shams University since 2011.

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    Omar Abdel-Rahman graduated from Faculty of Medicine, Ain Shams University on December 2005, obtained Master degree in Clinical Oncology since 2009, he is working currently as an assistant lecturer of Clinical Oncology, Ain Shams University since 2011.

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