Cetuximab for esophageal cancer: an updated meta-analysis of randomized controlled trials

Abstract

BackgroundIncreasing evidence indicates that cetuximab (CET) combined with chemoradiotherapy may be effective for patients with esophageal cancer. However, the recent results are still contradictory and no consensus has yet been reached on this issue. To evaluate the clinical effects and safety of CET, we conducted an updated meta-analysis by retrieving published data up to June 2018.MethodsA comprehensive literature search was performed in several electronic databases, including PubMed, Embase, the Cochrane Library, CNKI database and Chinese Biomedicine Database using subject terms and free terms. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to determine the efficiency and safety of CET.ResultsThis meta-analysis included 10 randomized controlled trials (RCTs). Five RCTs reported localized esophageal cancer and other five RCTs reported metastatic esophageal cancer. For these patients with localized esophageal cancer, CET could not significantly improve the response rate, overall survival and progression-free survival (PFS, 1–5 years). But CET treatment might increase the incidences of diarrhea (OR = 2.07; CI = 1.01–4.25) and rash (OR = 16.91; CI = 3.20–89.42). For other patients with metastatic esophageal cancer, the addition of CET significantly increased the response rate (OR = 3.34; CI = 1.90–5.88), disease control rate (OR = 2.92; CI = 1.49–5.71) and 2-year overall survival (OR = 2.78; CI = 1.20–6.46) compared with the control group. However, CET could not improve the 1-year overall survival and might make patients with metastatic esophageal cancer more susceptible to rash (OR = 5.50; CI = 2.14–14.14). No significant differences in other adverse effects were found between the two groups.ConclusionsOur findings suggested that adding CET to multimodal therapy significantly improved response rate and disease control rate for patients with metastatic esophageal cancer rather than patients with localized esophageal cancer. CET might be a safe therapeutic choice, but CET failed to significantly improve the overall survival and PFS for patients with localized or metastatic esophageal cancer.

Efficacy and safety of anti-epidermal growth factor receptor agents for the treatment of oesophageal cancer: a systematic review and meta-analysis

“…Erlotinib and cetuximab demonstrated notable beneficial effects on the DCR in OC, which was consistent with the results of previous studies. 48 57 Most meta-analyses have only reported results for mAb and TKI therapy, without specifying the individual drugs; therefore, it was impossible to verify the effectiveness of each drug.…”

“…However, cetuximab did not significantly increase the OS, which was consistent with the data from a previous report. 48 It has been suggested that the reduced efficacy of cetuximab in combination with CRT is due to proinflammatory and antitumour proliferative effects of this mAb. 49 Moreover, cetuximab may limit the free radical-induced DNA damage by platinum drugs, 50 which could also explain the non-significant outcomes in this meta-analysis.…”

“…An increased incidence of hypomagnesaemia was confirmed for cetuximab, in accordance with the data of another report. 48 Hypomagnesaemia, a frequent side effect of cetuximab, is a serious electrolyte abnormality associated with an increased risk of seizures and cardiac events. 64 The exact mechanism of cetuximab-induced hypomagnesaemia has not been well elucidated.…”

Advances in targeted therapy for esophageal cancer

“…According to Huang's report, for patients with ESCC with high EGFR expression, cetuximab could not only improve survival but also reduce the recurrence and metastatic potential of the tumor. 14 Combining cetuximab with chemotherapy drugs is a novel strategy for esophageal cancer therapy. Yar Saglam et al revealed that the combination of cetuximab and cucurbitacin B can significantly inhibit growth and migration of colorectal cancer cells.…”

Targeted Therapies and Immunotherapies in the Treatment of Esophageal Cancers

“…Unfortunately, cetuximab did not produce the same encouraging results for EC. A recent meta-analysis of 10 clinical trials over the past decade concluded that cetuximab (in combination with chemotherapy) did not demonstrate efficacy for improving survival of patients with either local or advanced EC, although it did improve the response rate in the latter [15]. Similarly, panitumumab, another anti-EGFR mAb, failed to improve survival in a phase III trial in which it was combined with chemotherapy [16].…”