Comparative Effectiveness of Neoadjuvant Treatments for Resectable Gastroesophageal Cancer: A Network Meta-Analysis

Background Several neoadjuvant treatments are available for patients with resectable gastroesophageal cancer. We did a Bayesian network meta-analysis (NMA) to compare available treatments, summarizing the direct and indirect evidence. Method We searched relevant databases for randomized controlled trials of neoadjuvant treatments for resectable gastroesophageal cancer which compared two or more of the following treatments: surgery alone, perioperative docetaxel, oxaliplatin, leucovorin, and fluorouracil (FLOT), and neoadjuvant treatments listed in National Comprehensive Cancer Network guideline. Then we performed a NMA to summarize the direct and indirect evidence to estimate the relative efficacy for outcomes including overall survival (OS), progression-free survival and R0 resection rate . We calculated odds ratio (OR) and hazard ratio (HR) with 95% credible intervals (CrI) for dichotomous data and time-to-event data respectively. We also calculated the surface under the cumulative ranking curve (SUCRA) value of each intervention to obtain a hierarchy of treatments. Result Eight eligible trials (2434 patients) were included in our NMA. The treatment with the highest probability of benefit on OS as compared with surgery alone was perioperative FLOT [HR = 0.58 with 95% CrI: (0.43, 0.78), SUCRA=92%], followed by preoperative radiotherapy, paclitaxel, and carboplatin (RT/PC) [HR = 0.68 with 95% CrI: (0.53, 0.87), SUCRA=72%], perioperative cisplatin with fluorouracil (CF) [HR = 0.70 with 95% CrI: (0.51, 0.95), SUCRA=67%] and perioperative epirubicin, cisplatin, and fluorouracil or capecitabine(ECF/ECX) [HR = 0.75 with 95% CrI: (0.60, 0.94), SUCRA=55%]. Conclusions Compared with surgery alone, perioperative CF, perioperative ECF/ECX, perioperative FLOT, and preoperative RT/PC significantly improved survival. Perioperative FLOT is likely to be the most effective neoadjuvant treatment for the disease. Further clinical studies are needed and justified.