Survival, recurrence and toxicity of HNSCC in comparison of a radiotherapy combination with cisplatin versus cetuximab: a meta-analysis

Abstract

Background: Cisplatin-based treatment has been considered the standard treatment regimen of HNSCC. Cetuximab is an emerging target therapy that has potential therapeutic benefits over cisplatin. Nevertheless, curative effects of cisplatin-based chemoradiotherapy (CRT) versus cetuximab-based bioradiotherapy (BRT) are still controversial.

Methods: Potentially eligible studies were retrieved using PubMed, Embase and Medline. Basic characteristics of patients and statistical data were collected. A meta-analysis model was established to compare CRT and BRT.

Results: Thirty-one eligible studies and 4212 patients were found. The pooled HRs with 95 % confidence intervals (CIs) for OS and PFS were 0.32 [0.09, 0.55] and 0.51 [0.22, 0.80], respectively, and both were in favor of cisplatin. However, 3-year survival and recurrence analysis of the subgroups showed no differences between the two groups (p > 0.05). In subgroup analysis, oropharyngeal primary tumors exhibited improved results by cetuximab with a pooled HR of 1.56 [1.14, 2.13] for PFS. Additionally, the HPV+ status was a significant factor in positive outcomes with cetuximab with a pooled HR of 1.12 [0.46, 2.17] for OS.

Conclusion: Long-term use of BRT showed no significant difference compared with CRT, and both arms showed different aspects of toxicity. In subgroup analysis, taking the effects of treatment and adverse events into consideration, cetuximab plus radiation may show superior responses regarding OS and PFS in patients who have HPV+ or primary oropharyngeal HNSCC, respectively, but physicians should administer them with caution.

Keywords: Adverse event; Cetuximab; Cisplatin; HNSCC; HPV; Oropharynx; Prognosis; Radiotherapy; Recurrence.

Fig. 1

Selection of Studies

Fig. 2

Meta-analysis estimated OS comparing cisplatin-based chemoradiotherapy versus cetuximab-based bioradiotherapy. (a) subgroup of estimation of 2-yr OS; (b) subgroup of estimation of 3-yr OS. OS, overall survival

Fig. 3

Meta-analysis compared cisplatin-based chemoradiotherapy versus cetuximab-based bioradiotherapy in estimating patients in HPV+ subgroup regarding to OS, PFS, and LRC. OS, overall survival; PFS, progression-free survival; LRC, locoregional control

Fig. 4

Meta-analysis compared cisplatin-based chemoradiotherapy versus cetuximab-based bioradiotherapy in estimating patients with oropharyngeal primary tumor regarding to OS, PFS and LRC. OS, overall survival; PFS, progression-free survival; LRC, locoregional control

Fig. 5

Meta-analysis estimated PFS comparing cisplatin-based chemoradiotherapy versus cetuximab-based bioradiotherapy. (a) subgroup of estimation of 2-yr PFS; (b) subgroup of estimation of 3-yr PFS. PFS, progression-free survival

Fig. 6

Meta-analysis estimated LRC comparing cisplatin-based chemoradiotherapy versus cetuximab-based bioradiotherapy. (a) subgroup of estimation of 2-yr LRC; (b) subgroup of estimation of 3-yr LRC. LRC, locoregional control

Fig. 7

Meta-analysis estimated DM comparing cisplatin-based chemoradiotherapy versus cetuximab-based bioradiotherapy. DM, distant metastasis

Fig. 8

Meta-analysis compared cisplatin-based chemoradiotherapy versus cetuximab-based bioradiotherapy in estimating toxicities including acute and late toxicities

Fig. 9

Meta-analysis compared cisplatin-based chemoradiotherapy versus cetuximab-based bioradiotherapy in estimating patients with oropharyngeal primary tumor and with single toxicity separately

Fig. 10

Sensitive analysis evaluated heterogeneity of OS cohort, PFS cohort and related subgroups. (a) Evaluation in OS group: total, 2-yr and 3-yr. (b) Evaluation in PFS group: total, 2-yr, and 3-yr. OS, overall survival; PFS, progression-free survival

Fig. 11

Estimated Begg’s funnel plots of publication bias regarding OS, PFS, LRC, and DM cohort respectively. OS, overall survival; PFS, progression-free survival; LRC, locoregional control; DM, distant metastasis