Chemotherapy and radiotherapy in locally advanced head and neck cancer: an individual patient data network meta-analysis.

BACKGROUND

Randomised, controlled trials and meta-analyses have shown the survival benefit of concomitant chemoradiotherapy or hyperfractionated radiotherapy in the treatment of locally advanced head and neck cancer. However, the relative efficacy of these treatments is unknown. We aimed to determine whether one treatment was superior to the other.

METHODS

We did a frequentist network meta-analysis based on individual patient data of meta-analyses evaluating the role of chemotherapy (Meta-Analysis of Chemotherapy in Head and Neck Cancer [MACH-NC]) and of altered fractionation radiotherapy (Meta-Analysis of Radiotherapy in Carcinomas of Head and Neck [MARCH]). Randomised, controlled trials that enrolled patients with non-metastatic head and neck squamous cell cancer between Jan 1, 1980, and Dec 31, 2016, were included. We used a two-step random-effects approach, and the log-rank test, stratified by trial to compare treatments, with locoregional therapy as the reference. Overall survival was the primary endpoint. The global Cochran Q statistic was used to assess homogeneity and consistency and P score to rank treatments (higher scores indicate more effective therapies).

FINDINGS

115 randomised, controlled trials, which enrolled patients between Jan 1, 1980, and April 30, 2012, yielded 154 comparisons (28 978 patients with 19 253 deaths and 20 579 progression events). Treatments were grouped into 16 modalities, for which 35 types of direct comparisons were available. Median follow-up based on all trials was 6·6 years (IQR 5·0-9·4). Hyperfractionated radiotherapy with concomitant chemotherapy (HFCRT) was ranked as the best treatment for overall survival (P score 97%; hazard ratio 0·63 [95% CI 0·51-0·77] compared with locoregional therapy). The hazard ratio of HFCRT compared with locoregional therapy with concomitant chemoradiotherapy with platinum-based chemotherapy (CLRT

INTERPRETATION

The results of this network meta-analysis suggest that further intensifying chemoradiotherapy, using HFCRT or IC

FUNDINGS

French Institut National du Cancer, French Ligue Nationale Contre le Cancer, and Fondation ARC.

Informations de copyright

Copyright © 2021 Elsevier Ltd. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests CP reports a grant from Fondation ARC during the conduct of the study. J-PP reports grants from Ligue National Contre le Cancer, during the conduct of the study. AA reports grants from Ligue Contre le Cancer and Programme Hospitalier de Recherche Clinique en Cancérologie–Institut National du Cancer, during the conduct of the study; grants from F Hoffmann-La Roche, and from the French Radiation and Oncology Group for Head and Neck (GORTEC), outside the submitted work. EEV and QTL report personal fees AbbVie, Amgen, AstraZeneca, Biolumina, BMS, Celgene, Eli Lilly, EMD Serono, Genentech, Merck, Regeneron, Novartis for EEV, and Grail for QTL outside the submitted work. J-WL reports grants from the US National Institutes of Health, during the conduct of the study. JJCH reports other payment from Sanofi Aventis during the conduct of the study; payment for an advisory role and conferences from Merck, Bristol Myers Squibb, Merck Sharp & Dohme España, Novartis, and Roche Pharma outside the submitted work. All other authors declare no competing interests.