The Efficacy and Safety of First-line Chemotherapy in Advanced Esophagogastric Cancer: A Network Meta-analysis
A partir d'une revue systématique de la littérature publiée jusqu'en juin 2015 sur des essais cliniques randomisés chez des patients atteints d'un cancer avancé de l'estomac, de l'œsophage ou de la jonction œsogastrique, cette méta-analyse en réseau évalue l'efficacité, du point de vue de la survie globale, et la toxicité de divers protocoles de chimiothérapie de première ligne
Background: A globally accepted standard first-line chemotherapy regimen in advanced esophagogastric cancer (AEGC) is not clearly established. We conducted a systematic review to investigate the efficacy and safety of first-line chemotherapy using Network meta-analysis (NMA). Methods: Medline, EMBASE, CENTRAL, and conferences were searched until June 2015 for randomized controlled trials that compared regimens containing: fluoropyrimidine (F), platinum (cisplatin [C] and oxaliplatin [Ox]), taxane (T), anthracycline (A), irinotecan (I), or methotrexate (M). Direct and indirect evidence for overall survival (OS) and progression-free-survival (PFS) were combined using random-effects NMA on the hazard ratio (HR) scale and calculated as combined hazard ratios and 95% credible intervals (CrIs). Results: The NMA incorporated 17 chemotherapy regimens with 37 direct comparisons between regimens for OS (50 studies, n = 10 249) and 29 direct comparisons for PFS (34 studies, n = 7795). Combining direct and indirect effects showed increased efficacy for fluoropyrimidine noncisplatin doublets (F-doublets) over cisplatin doublets (C-doublets): FI vs CF (combined HR = 0.85, 95% CrI = 0.71 to 0.99), FOx vs CF (combined HR = 0.83, 95% CrI = 0.71 to 0.98) in OS and FOx vs CF (combined HR = 0.82, 95% CrI = 0.66 to 0.99) in PFS. Anthracycline-containing triplets (A-triplets: ACF, AFOx, AFM) and TCF triplet showed no benefit over F-doublets in OS and PFS. The triplet FOxT showed increased PFS vs F-doublets FT (combined HR = 0.61, 95% CrI = 0.38 to 0.99), FI (combined HR = 0.62, 95% CrI = 0.38 to 0.99), and FOx (combined HR = 0.67, 95% CrI = 0.44 to 0.99). Increased grade 3 to 4 toxicity was found for CF vs F-doublets, for ACF vs FI for TCF vs CF, and for FOxT vs FOx. Conclusions: Based on efficacy and toxicity, F-doublets FOx, FI, and FT are preferred as first-line treatment for AEGC compared with C-doublets, A-triplets, and TCF. FOxT is the most promising triplet.