Anti-Epidermal Growth Factor Receptor (EGFR) Monoclonal Antibody combined with Cisplatin and 5-Fluorouracil in Patients with Metastatic Nasopharyngeal Carcinoma after Radical Radiotherapy: A Multicentre, Open-label, Phase II Clinical Trial

Abstract

Background

We conducted a single-arm phase II trial to evaluate the efficacy and adverse effects (AEs) of an anti-epidermal growth factor receptor (EGFR) monoclonal antibody, nimotuzumab, combined with cisplatin and 5-fluorouracil (PF) as first-line treatment in recurrent metastatic nasopharyngeal carcinoma (rmNPC) after radical radiotherapy.

Methods

Patients who met the eligibility criteria were recruited from ten institutions (ClinicalTrials.gov; NCT01616849). A Simon optimal two-stage design was used to calculate the sample size. All patients received weekly nimotuzumab (200 mg) added to cisplatin (100 mg/m² D1) and 5-fluorouracil (4 g/m² continuous infusion D1-4) every 3-weekly for a maximum of 6 cycles. Primary endpoint was objective response rate (ORR). Secondary endpoints included disease control rate (DCR), progression free survival (PFS), overall survival (OS) and AEs.

Results

35 patients were enrolled (13 in stage 1 and 22 in stage 2). Overall ORR and DCR were 71.4% (25/35) and 85.7% (30/35), respectively. Median PFS and OS were 7.0 (95% CI 5.8-8.2) mo and 16.3 (95% CI 11.4-21.3) mo, respectively. Unplanned exploratory analyses suggest that patients who received ≥2400 mg nimotuzumab and ≥4 cycles of PF had superior ORR, PFS and OS than those who did not (88.9% vs. 12.5%, P < 0.001; 7.4 mo vs. 2.7 mo, P = 0.081; 17.0 mo vs. 8.0 mo, P = 0.202). Favourable subgroups included patients with lung metastasis (HROS 0.324 [95% CI = 0.146-0.717], P = 0.008) and disease-free interval of > 12 mo (HROS 0.307 [95% CI = 0.131-0.724], P = 0.004), but no difference was observed for metastatic burden. The only major grade 3/4 AE was leukopenia (62.9%).

Conclusion

Combination nimotuzumab-PF chemotherapy demonstrates potential efficacy, and is well tolerated as first-line chemotherapy regimen in rmNPC.

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