P-26 RATIONALE 305: Tislelizumab plus chemotherapy versus placebo plus chemotherapy as first-line therapy in patients with gastric or gastroesophageal junction adenocarcinoma

Abstract

recent years and, although several authors compared the two ablative modalities, it remains unclear which technique results in better clinical outcomes. Thus, we performed a systematic review and meta-analysis to compare percutaneous MWA versus percutaneous RFA in BCLC-A HCC in randomized controlled trials (RCTs), especially focusing on five outcomes of interest in this specific patient subpopulation.Methods: We performed a systematic review and meta-analysis according to PRISMA guidelines to evaluate the clinical role of MWA and RFA in BCLC-A HCC in terms of complete ablation (CA) rate, local recurrence (LR) rate, overall survival (OS) rate at 1 year, OS rate at 3 years and major complications rate. All phase II and phase III RCTs published from June 15, 2008, to February 6, 2020, comparing MWA and RFA in BCLC-A HCC were retrieved through PubMed/Med, Cochrane library and EMBASE. Five eligible studies involving a total of 794 patients (MWA: 409; RFA: 385) and 1008 nodules of HCC (MWA: 519; RFA: 489) were included in our analysis. Results about CA, LR, OS and major complications rate were compared by calculating Odds ratios (OR) with 95% confidence intervals (CIs); ORs were combined with the Mantel-Haenszel method. Statistical heterogeneity between studies was examined using the Chi-square test and the I2 statistic; substantial heterogeneity was considered to exist when the I2 value was greater than 50% or there was a low P-value (< 0.10) in the Chi-square test. The risk of bias in the five selected studies was assessed using the Cochrane Collaboration tool for assessing risk of bias, including selection, performance, detection, attrition and reporting bias.Results: No differences in CA rate (OR¼1.21; 95% CI 0.52-2.80, I2 5%), LR rate (OR¼0.78; 95% CI 0.36-1.69, I2 60%), OS at 3 years (OR¼1.17; 95% CI 0.81-1.70, I2 0%) and major complications rate (OR¼1.11; 95% CI 0.55-2.23, I2 32%) between percutaneous MWA and percutaneous RFA were detected in the analysis. Regarding OS at 1 year, a higher rate was observed for the MWA group (OR¼1.9; 95% CI 1.03-3.51, I2 32%). All studies included in our analysis were judged as studies with a low risk of bias in separate reviews of 4 authors. Conclusion:The comparison between MWA and RFA is currently under debate, with several meta-analyses finding similar efficacy and safety between the two modalities. However, previous studies presented several limitations, given the inclusion of primary and secondary liver malignancies and HCC at different stages; moreover, most of the experience comparing the two modalities comes from retrospective analyses of single-center cohorts, with no level 1 data supporting the superiority of RFA or MWA. In our study, MWA resulted in better survival at 1 year, although this benefit was not confirmed in the 3-year analysis. Well-designed, multicenter RCTs with large sample sizes are further required to confirm the above results.

Recent Progress in Immunotherapy for Gastric Cancer

“…With the same rationale, the ongoing phase III RATIONALE-305 trial (NCT03777657) is a global, double-blind, placebo-controlled, randomized, phase III study evaluating tislelizumab plus platinum-based doublet chemotherapy vs. placebo plus chemotherapy as a first-line treatment for patients with HER2-negative AGC [ 31 ]. A total of 997 patients from 13 countries were enrolled regardless of PD-L1 status.…”

Recent advances in the progress of immune checkpoint inhibitors in the treatment of advanced gastric cancer: A review

“…The median PFS was 6.1 months, and the 1-year OS rate was 62%, which had not reached the median OS ( 41 ). Subsequently, a large randomized, double-blind, placebo-controlled phase III trial was conducted to study the efficacy and safety of tislelizumab combined with first-line chemotherapy in patients with advanced G/GEJA, and the trial is ongoing ( 42 ).…”

Complete remission of alpha-fetoprotein-producing gastric cancer by combined tislelizumab-apatinib treatment of a patient with proficient mismatch repair: a case report

“…In the Rationale 205 study (NCT03469557), tislelizumab plus chemotherapy produced durable responses with manageable tolerability as first-line treatment of patients with advanced esophageal squamous cell carcinoma or gastric/gastroesophageal junction adenocarcinoma [ 4 ]. A worldwide multicenter phase 3 trial, Rationale 305 ((NCT03777657), is in progress to assess tislelizumab with chemotherapy versus placebo plus chemotherapy as first-line treatment of patients with gastric or gastroesophageal junction cancer [ 5 ].…”