Randomized controlled trial in gastric or gastroesophageal junction adenocarcinoma undergoing systemic therapy over two decades.

INTRODUCTION

The number of randomized controlled trials (RCTs) investigating the systemic treatment of gastric or gastroesophageal junction adenocarcinoma (GA-RCTs) is increasing. We aimed to describe the characteristics and evaluate the clinical benefit of GA-RCTs over the past 20 years.

MATERIALS AND METHODS

We searched for RCTs of systemic treatment in GA published in eight major journals between 2001 and 2020 in PubMed. From the included studies, the characteristics and results of GA-RCTs were extracted. Clinical benefit was assessed using the European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS).

RESULTS

About 93 RCTs with 38365 patients were included. Seventy-one (76.3%) studies received external funding, with an increase from 27.3% (2001-2005) to 94.1% (2016-2020). RCTs on targeted therapy and/or immunotherapy have also increased over time, but only 14 (41.2%) were restricted to specific biomarkers. Forty-four (47.3%) studies met their primary endpoint (defined as positive RCTs), but median overall survival has not improved over time. Moreover, only 16 (36.4%) studies met the ESMO-MCBS threshold. RCTs whose study design and results met the ESMO-MCBS thresholds has not increased over time (p = 0.827 and p = 0.733, respectively).

CONCLUSIONS

GA-RCTs are increasingly focused on targeted therapy and/or immunotherapy, and are more likely to receive external funding. However, the effect size has not shown significant improvement in the past 20 years. Only a few RCTs with positive results met ESMO thresholds. Future RCTs should prioritize the clinical benefits and provide direct evidence to optimize and reform GA treatment practices.