Combination treatment with cetuximab in advanced nasopharyngeal carcinoma patients: a meta-analysis

Abstract

Purpose: Cetuximab, an anti-epidermal growth factor receptor monoclonal antibody, carries the potential for combination treatment against nasopharyngeal carcinoma (NPC). We conducted a meta-analysis to assess the possible benefits and safety between the combination treatment with cetuximab and conventional treatment in NPC patients. Skin toxicity (ST) associated with additional cetuximab was evaluated as well.

Methods: We performed a systematic search (PubMed, Embase, Cochrane library, China National Knowledge Infrastructure, and WanFang Data) for studies comparing combination treatment with cetuximab versus conventional treatment in NPC patients. The selected studies included completely or partly reported clinical outcomes including survivals, complete and partial responses, and adverse reactions (ST). The pooled HR, relative risk (RR), and respective 95% CI were estimated by using fixed effects model or random effects model.

Results: A total of 23 relevant studies with available data were included in the final analysis. According to the pooled data, combination treatment with cetuximab showed improved efficacy on increased objective response rate (studies with cetuximab treatment: RR: 1.39, 95% CI: 1.29-1.50; concurrent chemoradiotherapy with or without cetuximab: RR: 1.39, 95% CI: 1.25-1.54) and prolonged survival (studies with cetuximab treatment: the pooled HR for OS was 0.70, 95% CI: 0.55-0.89; concurrent chemoradiotherapy with or without cetuximab: the pooled HR for OS was 0.64, 95% CI: 0.49-0.84) compared with conventional treatment. Moreover, the improved efficacy was invariably accompanied by an increased occurrence of ST (studies with cetuximab treatment: RR: 2.46, 95% CI: 1.81-3.34; concurrent chemoradiotherapy with or without cetuximab: RR: 1.84, 95% CI: 1.02-3.31). However, the majority of adverse reactions exhibited similar occurrence rates between the different treatments.

Conclusion: Patients with NPC receiving additional cetuximab treatment can benefit more from this systemic comprehensive therapy, while the efficiency of conventional treatment for NPC is limited. ST associated with cetuximab may be used as a potential on-treatment marker to guide treatment with cetuximab against NPC.

Keywords: cetuximab; clinical outcomes; combination treatment; nasopharyngeal carcinoma.

Figure 1

Flow diagram of selection process of studies.

Figure 2

(A) Forest plot of combination treatment with cetuximab versus conventional treatment on outcome of survival (OS, PFS, DMFS, and DFS). (B) Forest plot of treatment of concurrent chemoradiotherapy with or without cetuximab on outcome of survival (OS, PFS, DMFS, and DFS). Abbreviations: OS, overall survival; PFS, progression-free survival; DMFS, distant metastasis-free survival; DFS, disease-free survival.

Figure 2

(A) Forest plot of combination treatment with cetuximab versus conventional treatment on outcome of survival (OS, PFS, DMFS, and DFS). (B) Forest plot of treatment of concurrent chemoradiotherapy with or without cetuximab on outcome of survival (OS, PFS, DMFS, and DFS). Abbreviations: OS, overall survival; PFS, progression-free survival; DMFS, distant metastasis-free survival; DFS, disease-free survival.

Figure 3

(A) Forest plot of combination treatment with CTX versus conventional treatment on the outcome of response rate (ORR). (B) Forest plot of treatment of concurrent chemoradiotherapy with or without cetuximab, IMRT with or without cetuximab, chemotherapy with or without cetuximab on ORR. Abbreviations: CCRT, concurrent chemoradiotherapy; Chem, chemotherapy; CTX, cetuximab; IMRT, intensity-modulated radiotherapy.

Figure 4

(A) Forest plot of combination treatment with cetuximab versus conventional treatment on outcome of adverse reactions (except skin toxicity). (B) Forest plot of treatment of concurrent chemoradiotherapy with or without cetuximab on outcome of adverse reactions (except skin toxicity).

Figure 4

(A) Forest plot of combination treatment with cetuximab versus conventional treatment on outcome of adverse reactions (except skin toxicity). (B) Forest plot of treatment of concurrent chemoradiotherapy with or without cetuximab on outcome of adverse reactions (except skin toxicity).

Figure 5

(A) Forest plot of combination treatment with cetuximab versus conventional treatment on outcome of skin toxicity (ST). (B) Forest plot of treatment of concurrent chemoradiotherapy with or without cetuximab on outcome of ST.