Chemotherapy and radiotherapy in XXXX : an update of the MAC-NPC meta-analysis.

@entity1 @entity5 @entity189
BACKGROUND: A previous individual @entity1 data meta-analysis by the Meta-Analysis of Chemotherapy in @entity189 (MAC-NPC) collaborative group to assess the addition of chemotherapy to radiotherapy showed that it improves overall survival in @entity189 . This benefit was restricted to @entity1 receiving concomitant chemotherapy and radiotherapy. The aim of this study was to update the meta-analysis, include recent trials, and to analyse separately the benefit of concomitant plus adjuvant chemotherapy. METHODS: We searched PubMed, Web of Science, Cochrane Controlled Trials meta-register, ClinicalTrials.gov, and meeting proceedings to identify published or unpublished randomised trials assessing radiotherapy with or without chemotherapy in @entity1 with non-metastatic @entity189 and obtained updated data for previously analysed studies. The primary endpoint of interest was overall survival. All trial results were combined and analysed using a fixed-effects model. The statistical analysis plan was pre-specified in a protocol. All data were analysed on an intention-to-treat basis. FINDINGS: We analysed data from 19 trials and 4806 @entity1 . Median follow-up was 7  7 years (IQR 6  2-11  9). We found that the addition of chemotherapy to radiotherapy significantly improved overall survival (hazard ratio [HR] 0  79, 95% CI 0  73-0  86, p<0  0001; absolute benefit at 5 years 6  3%, 95% CI 3  5-9  1). The interaction between treatment effect (benefit of chemotherapy) on overall survival and the timing of chemotherapy was significant (p=0  01) in favour of concomitant plus adjuvant chemotherapy (HR 0  65, 0  56-0  76) and concomitant without adjuvant chemotherapy (0  80, 0  70-0  93) but not adjuvant chemotherapy alone (0  87, 0  68-1  12) or induction chemotherapy alone (0  96, 0  80-1  16). The benefit of the addition of chemotherapy was consistent for all endpoints analysed (all p<0  0001): progression-free survival (HR 0  75, 95% CI 0  69-0  81), locoregional control (0  73, 0  64-0  83), distant control (0  67, 0  59-0  75), and @entity5 mortality (0  76, 0  69-0  84). INTERPRETATION: Our results confirm that the addition of concomitant chemotherapy to radiotherapy significantly improves survival in @entity1 with locoregionally advanced @entity189 . To our knowledge, this is the first analysis that examines the effect of concomitant chemotherapy with and without adjuvant chemotherapy as distinct groups. Further studies on the specific benefits of adjuvant chemotherapy after concomitant chemoradiotherapy are needed. FUNDING: French Ministry of Health (Programme d'actions int  gr  es de recherche VADS), Ligue Nationale Contre le @entity5 , and Sanofi-Aventis.
