Concurrent Chemoradiotherapy with or without Anti-EGFR-Targeted Treatment for Stage II-IVb Nasopharyngeal Carcinoma: Retrospective Analysis with a Large Cohort and Long Follow-up

Abstract

We examined the benefits of the combination of anti-EGFR targeted treatment, cetuximab (CTX) or nimotuzumab (NTZ) and concurrent platinum-based chemoradiotherapy (CCRT) compared with CCRT alone in patients with stage II - IVb nasopharyngeal carcinoma (NPC). A total of 1,628 eligible patients with stage II - IVb NPC, who received CCRT (three cycles of 100 mg/m2 cisplatin every 3 weeks with intensity-modulated radiotherapy) with or without CTX or NTZ between June 2009 and December 2013 were included in the analysis. Using propensity scores to adjust for potential prognostic factors, a well-balanced cohort of 878 patients was created by matching each patient who received CTX or NTZ plus CCRT with no more than four patients who received CCRT alone (1:4). Efficacy and safety were compared between CTX/NTZ plus CCRT and CCRT alone arms. Compared with CCRT alone, treatment with CTX/NTZ plus CCRT was associated with a significantly increased overall survival (3-year OS, 96.6% vs. 92.9%, P = 0.015), improved disease-free survival (3-year DFS, 93.5% vs 86.9%, P = 0.028), and improved distant metastasis-free survival (3-year DMFS, 94.6% vs 89.3%, P = 0.030). Increased rate of CTX related-skin reaction and mucositis was observed in the CTX plus CCRT arm. Multivariate analysis demonstrated the combination of CTX/NTZ was a significant protective factor for OS, DFS, and DMFS in patients treated with CCRT. Our analysis suggests that the addition of CTX/NTZ to CCRT is more effective for maximizing survival in patients with stage II-IVb NPC compared with CCRT alone.

Anti‐epidermal growth factor receptor therapy concurrently with induction chemotherapy in locoregionally advanced nasopharyngeal carcinoma

“…Although CCRT is effective, it may be not powerful enough to reduce distant metastasis for advanced disease . You et al and Li et al enhanced the treatment intensity during concurrent phase by adding CTX/NTZ to standard concomitant cisplatin. However, the efficacy may be unsatisfactory.…”

“…4,25 Although CCRT is effective, it may be not powerful enough to reduce distant metastasis for advanced disease. 26 You et al 13 Actually, IC followed by CCRT is a preferable treatment modality for its better compliance and excellent efficacy 16,17,19 compared with CCRT with AC. In our current study, we provide a new insight in improving survival outcomes by enhancing the treatment during induction phase.…”

“…Epidermal growth factor receptor (EGFR), a transmembrane protein highly expressed in most human epithelial malignancies, is a promising therapeutic target in oncology for its correlation with aggressive phenotype, treatment resistance and poor prognosis . EGFR is also highly expressed in NPC and numerous studies have evaluated the efficacy of anti‐EGFR targeted therapy . Cetuximab (CTX) or nimotuzumab (NTZ) (anti‐EGFR monoclonal antibodies) concurrent with RT could achieve comparable outcomes compared with standard cisplatin‐RT .…”

“…12,14 When combined with CCRT, different results were produced. You et al 13 and Xia et al 11 revealed that CTX/NTZ additional to CCRT was more effective than CCRT alone, while Li et al 10 did not identify any difference. Regardless of the controversial efficacy, CTX/NTZ significantly increased the incidence of acute mucositis and acneiform rash during RT, 10,12 resulting in poor quality of life or even disruption of RT.…”

“…6,7 EGFR is also highly expressed in NPC 8 and numerous studies have evaluated the efficacy of anti-EGFR targeted therapy. [9][10][11][12][13][14][15] Cetuximab (CTX) or nimotuzumab (NTZ) (anti-EGFR monoclonal antibodies) concurrent with RT could achieve comparable outcomes compared with standard cisplatin-RT. 12,14 When combined with CCRT, different results were produced.…”