Individual Participant Data Network Meta-Analysis of Neoadjuvant Chemotherapy or Chemoradiotherapy in Esophageal or Gastroesophageal Junction Carcinoma
Matthieu Faron, M. Cheugoua-Zanetsie, Jayne F. Tierney, P. Thirion, Matthew Nankivell, Kathryn Winter, Hong Yang, Joël Shapiro, Déwi Vernerey, B. Mark Smithers, T. N. Walsh, Guillaume Piessen, Magnus Nilsson, Jurjen J. Boonstra, Marc Ychou, Simon Law, David Cunningham, Florent de Vathaire, M. Stahl, Susan G. Urba, Michele Valmasoni, D. Williaume, Janine Thomas, Florian Lordick, Joel E. Tepper, Jack A. Roth, Val Gebski, Bryan Burmeister, Xavier Paolettí, Johanna van Sandick, Jianhua Fu, Jean‐Pierre Pignon, Michel Ducreux, Stefan Michiels, on behalf of the MANATEC-02 Collaborative Group, Chanvitan Apinop, Anne Arezina, Emilie Barbier, Gary Alan Bass, Pierre Blanchard, Jurjen J. Boonstra, Jean-François Bosset, Bryan Burmeister, M. Cheugoua-Zanetsie, David Cunningham, Michel Ducreux, Matthieu Faron, Jianhua Fu, Val Gebski, D.J. Girling, David P. Kelsen, Fredrik Klevebro, Simon Law, É. Le Prisé, Florian Lordick, Tanaphon Maipang, Murielle Mauer, Stefan Michiels, Jennifer Moughan, Matthew Nankivell, K. Nygaard, Patrick Owens, Xavier Paolettí, Guillaume Piessen, Jean‐Pierre Pignon, Jean-Luc Raoul, Jack Roth, Alberto Ruol, P. Schlag, Christoph Schumacher, Joël Shapiro, B. Mark Smithers, M. Stahl, Joel E. Tepper, P. Thirion, Janine Thomas, Jayne F. Tierney, Susan Urba, Michele Valmasoni, Ate van der Gaast, Johanna van Sandick, D. Williaume, Kathryn Winter, John Wong, Hong Yang, Marc Ychou
Abstract
PURPOSE The optimal neoadjuvant treatment for resectable carcinoma of the thoracic esophagus (TE) or gastroesophageal junction (GEJ) remains a matter of debate. We performed an individual participant data (IPD) network meta-analysis (NMA) of randomized controlled trials (RCTs) to study the effect of chemotherapy or chemoradiotherapy, with a focus on tumor location and histology subgroups. PATIENTS AND METHODS All, published or unpublished, RCTs closed to accrual before December 31, 2015 and having compared at least two of the following strategies were eligible: upfront surgery (S), chemotherapy followed by surgery (CS), and chemoradiotherapy followed by surgery (CRS). All analyses were conducted on IPD obtained from investigators. The primary end point was overall survival (OS). The IPD-NMA was analyzed by a one-step mixed-effect Cox model adjusted for age, sex, tumor location, and histology. The NMA was registered in PROSPERO (CRD42018107158). RESULTS IPD were obtained for 26 of 35 RCTs (4,985 of 5,807 patients) corresponding to 12 comparisons for CS-S, 12 for CRS-S, and four for CRS-CS. CS and CRS led to increased OS when compared with S with hazard ratio (HR) = 0.86 (0.75 to 0.99), P = .03 and HR = 0.77 (0.68 to 0.87), P < .001 respectively. The NMA comparison of CRS versus CS for OS gave a HR of 0.90 (0.74 to 1.09), P = .27 (consistency P = .26, heterogeneity P = .0038). For CS versus S, a larger effect on OS was observed for GEJ versus TE tumors ( P = .036). For the CRS versus S and CRS versus CS, a larger effect on OS was observed for women ( P = .003, .012, respectively). CONCLUSION Neoadjuvant chemotherapy and chemoradiotherapy were consistently better than S alone across histology, but with some variation in the magnitude of treatment effect by sex for CRS and tumor location for CS. A strong OS difference between CS and CRS was not identified.