The effect of cytotoxic chemotherapy on the risk of high-grade acneiform rash with cetuximab in cancer patients: A meta-analysis.

Abstract

9072 Background: Cetuximab, an epidermal growth factor receptor (EGFR) inhibitor monoclonal antibody, is approved for head and neck cancer in combination with radiotherapy and for colorectal cancer as single agent or combined with irinotecan. Its combined use with chemotherapy in these and other types of cancer has been undergoing active investigation. Papulopustular rash (acneiform rash) is the most common adverse effect. This analysis was done to investigate the risk of high-grade (grade ≥3) acneiform rash in a setting of cetuximab in combination with cytotoxic chemotherapy. Methods: Relevant studies were identified from PubMed (1998 to 2009) and abstracts presented at the American Society of Clinical Oncology Conferences between 2004 and 2009. Eligible studies were limited to prospective randomized controlled Phase II-III clinical trials in which cancer patients were treated with cetuximab 400 mg/m2 initially, followed by weekly 250 mg/m2, in combination with chemotherapy. Incidence, relative risk (RR), and 95% confidence intervals were calculated using random-effects or fixed-effects models based on the heterogeneity of included studies. Results: A total of 5,272 patients with a variety of solid cancers from 13 randomized controlled clinical trials were included for analysis. The overall incidence of high-grade acneiform rash associated with cetuximab in combination with chemotherapy was 10.3% (95% CI: 7.6-13.9%). There was a significantly increased risk of high grade acneiform rash with cetuximab in combination with chemotherapy in comparison with controls (chemotherapy alone) (RR=37.8, 95% CI: 16.8-85.4%, p value<0.001). When compared to our previous analysis of high-grade acneiform rash with cetuximab monotherapy (6.5%), patients receiving combination treatment are at increased risk of developing severe acneiform rash (RR=1.6, 95% CI: 1.2-2.0%, p-value<0.0001). Conclusions: Cancer patients treated with cetuximab in combination with cytotoxic chemotherapy are at substantial risk for developing high-grade acneiform rash. The addition of chemotherapy may significantly increase the risk of rash associated with cetuximab. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb, ImClone Systems Bristol-Myers Squibb Bristol-Myers Squibb, ImClone Systems, Novartis, Onyx Pharmaceuticals, Pfizer, Wyeth Hana Biosciences