Comparison of Available Treatment Strategies and Chemotherapeutic Options for Locally Advanced Head and Neck Cancer

Network meta-analysis clarifies that concurrent chemoradiotherapy with cisplatin is the gold standard of treatment

In an article published recently in Oral Oncology, Oreste Iocca of the Department of Otolaryngology-Head and Neck Surgery, Regina Elena National Cancer Institute, IRCCS, Rome, Italy and collaborators performed a comprehensive synthesis of the available evidence on systemic therapies and radiotherapy for locally advanced head and neck cancer. The analysis provided answers to some unresolved issues in the management of patients with head and neck cancer. 

The analysis is the result of an intense work of research and data analysis in which the study team compared directly and indirectly different treatment options for locally advanced head and neck cancer. The main findings clarify that concurrent chemoradiotherapy with cisplatin is the gold standard of treatment. It also showed that alteration of fractionation does not have a role when concurrent chemoradiotherapy is feasible. This is the first time these outcomes are analyzed specifically for locally advanced head and neck cancer patients. 

In the study background, the authors explained that there are many unresolved questions in the management of locally advanced head and neck cancer. Many chemotherapy drugs and radiotherapy fractionation schemes are available but not all have been evaluated in head-to-head clinical trials. They performed the systematic review and Bayesian network meta-analysis with aim to compare the available treatment strategies and chemotherapeutic options for locally advanced head and neck cancer. 

The study team performed a search of literature databases, trials registries and meeting proceedings for published and unpublished randomised trials from 1st January 2000 to 1st December 2017. It was required that the trials compare systemic interventions and radiotherapy approaches for locally advanced, non-metastatic head and neck cancer. 

Trials that recruited patients for whom surgery was the first treatment option, sample size less than 20 per arm or that did not use randomisation for treatment allocation were excluded from the analysis. 

Summary estimates on overall survival (OS), progression-free survival (PFS) and toxicity outcomes (grade 3–4 mucositis and neutropenia) were extracted from the included studies on a predefined database sheet. Bias was assessed through the Cochrane risk of bias assessment tool. A set of pair-wise meta-analyses using a random effect model has been performed, as well as a random effect network meta-analysis under a Bayesian framework. 

From the 57 included trials with enrolled 15,723 patients, it was possible to conduct analysis on 26 treatments in terms of OS, 22 treatments for PFS and 10 treatments for toxicity. 

In terms of OS, concurrent chemoradiotherapy (CCRT) with cisplatin (hazard ratio, HR 0.70) and cetuximab on top of CCRT (HR 0.7) are clearly superior to conventional radiotherapy (RT) alone. Induction chemotherapy (IC) with cisplatin and fluorouracil (HR 0.74), IC with docetaxel, cisplatin, fluorouracil (HR 0.55) and IC with paclitaxel, cisplatin, fluorouracil (HR 0.55) before CCRT are all superior to conventional RT. CCRT with cisplatin is also superior to altered fractionation RT (HR 0.74). Altered fractionation RT is not superior to conventional RT (HR 0.95). 

Regarding PFS, CCRT with cisplatin (HR 0.72), cisplatin and fluorouracil (HR 0.67), carboplatin (HR 0.63), carboplatin and fluorouracil (HR 0.75), IC with cisplatin and fluorouracil (HR 0.59), IC with docetaxel, cisplatin and fluorouracil (HR 0.53) and IC with paclitaxel, cisplatin and fluorouracil (HR 0.59) are superior to conventional RT and altered fractionation RT. The IC with docetaxel, cisplatin and fluorouracil shows a significant superiority against CCRT with cisplatin (HR 0.73). Altered fractionation RT is not superior to conventional RT (HR 0.91). 

Altered fractionation increases the risk of developing grade 3–4 mucositis compared to conventional RT (OR 3.74). 

The authors concluded that CCRT with cisplatin remains the gold standard of treatment. Taxane based IC regimens may have an impact on locally advanced disease. Altered fractionation RT is inferior to CCRT and also does not seem to be meaningfully better than conventionally fractionated RT alone. Its role in locally advanced disease should be re-evaluated according to Dr Iocca and colleagues. 

Reference 

Iocca O, Farcomeni A, Di Rocco A, et al. Locally advanced squamous cell carcinoma of the head and neck: A systematic review and Bayesian network meta-analysis of the currently available treatment options. Oral Oncology 2018; 80:40–51. https://doi.org/10.1016/j.oraloncology.2018.03.001