Nimotuzumab combined with paclitaxel and cisplatin as first-line treatment for metastatic esophageal squamous cell carcinoma: A prospective, multicenter, double-blind, randomized controlled clinical study.

4055 Background: Chemotherapy for advanced esophageal squamous cell carcinoma (ESCC) is limited due to the lack of effective drugs. Such as traditional two drugs chemotherapy (5-Fluorouracil and Cisplatin) as first-line treatment for metastatic and recurrent ESCC has an efficacy of 25-35%. Nimotuzumab is an anti-epidermal growth factor receptor (EGFR) monoclonal antibody. Previous studies have shown that its combination with paclitaxel and cisplatin (TP regimen) has a good efficacy, with an objective response rate (ORR) of up to 55%, median overall survival (mOS) 13.9 months in some small-sample trials. Methods: Eligible patients from 36 centers in China, who were randomly assigned to receive nimotuzumab (400 mg once per week, up to 2 years) or placebo followed by TP regimen (paclitaxel 175 mg/m², cisplatin 60 mg/m², Day 1, with a 21-day cycle, up to 6 cycles) until disease progression or unacceptable toxicity. The primary end point was overall survival (OS) and the secondary end points were progression-free survival (PFS), response rates, quality of life (QoL) and safety. Results: A total of 640 patients were screened. 503 patients were enrolled and 161 patients with EGFR gene amplification tumors were eligible. In the full analysis set of 497 patients who had took at least one dose of medication, there were no differences in baseline characteristics. The mOS were 12 vs 11.5 months, and the median PFS were 5.6 vs 5.4 months respectively, suggesting survival benefit trend in the trial. ORR were 55.5% and 50.4% for both arms. In the EGFR gene amplification subgroup, the mOS was 13.3 vs 9.5 months (log-rank test, hazard ratio [HR] = 0.66 (95%CI, [0.47-0.93]), P = 0.016) for two groups. Patients who were with ESCC at stage IV, as well as who had not undergone surgery, radical radiotherapy, or neoadjuvant and adjuvant therapy showed significant survival benefits after the addition of nimotuzumab. Median PFS were 6.0 vs 5.5 months for two arms (log-rank test, HR = 0.63 [0.43-0.91], P = 0.014). Both OS and PFS were longer in the nimotuzumab group than in the placebo group. The ORR of the two groups were 61.3% and 44.0%, respectively (P = 0.029). There were no statistically significant differences in the QoL scores of the FAS population at each time point before and after treatment. The incidence of adverse events were comparable in the experimental group and the control group. Such as the incidence of serious adverse event (SAE) was 30.7% and 34.5%, serious adverse drug reaction (SADR) was 2.7% and 8.3%, the incidence of above grade 3 treatment emergent adverse event (TEAE) was 85.3% and 83.3%, respectively, etc. Conclusions: In patients with metastatic EGFR gene amplification ESCC, nimotuzumab plus TP as first-line treatment significantly improved OS and PFS with a good safety profile.