Abstract 434P
Background
Recently, several positive trials assessing different immunotherapy treatments in combination with chemotherapy(CTh) as first-line treatment have been reported. However, direct comparison among immune checkpoint inhibitors-based therapy is lacking. This network meta-analysis (NMA) aims to indirectly compare the efficacy and the safety of adding immunotherapy to oxaliplatin-based CTh versus CTh alone in patients with HER2-negative gastric and gastroesophageal junction (G/GEJ) cancer.
Methods
A thorough research was conducted on PubMed, Web of Science, Cochrane, and Scopus databases and major international medical oncology conferences to retrieve phase 3 randomized clinical trials (RCTs) that compared immunotherapy plus CTh to CTh alone. The primary outcome was overall survival (OS) in all comers and in predefined PD-L1-positive subgroup. The NMA was conducted using RStudio version 2023.12.0+369 and the netmeta package.
Results
Six RCTs were included in this NMA, compromising 6010 patients. The NMA showed that sintilimab plus CTh was the best to improve OS in all comers (HR = 0.76; 95% CI: 0.63-0.94) and in predefined PD-L1-positive subgroup (HR = 0.65; 95% CI: 0.50-0.86). Pembrolizumab plus CTh ranked as second in all comers (HR = 0.78; 95% CI: 0.70- 0.87) while nivolumab plus CTh ranked as second in predefined PD-L1-positive subgroup (HR = 0.71; 95% CI: 0.59- 0.86). Nivolumab plus CTh and sugemalimab plus CTh were the best at improving the ORR (RR = 1.23; 95% CI: 1.13-1.34) in all comers and (RR = 1.30; 95% CI: 1.10-1.52) in predefined PD-L1-positive subgroup, respectively. Sugemalimab plus CTh has the least TRAEs of grade ≥ 3 (RR = 1.08; 95% CI: 0.94, 1.25). Subgroup analysis showed that sintilimab plus CTh was the best for male patients and those <65 years, while sugemalimab plus CTh was the best for female patients and those with an age ≥ 65 years.
Conclusions
The NMA suggests that sintilimab plus CTh is the optimal first-line treatment for patients with HER2-negative G/GEJ cancer regardless of PD-L1 expression. However, subgroup analysis demonstrated that certain factors can impact the optimal treatment choice. Accordingly, personalizing therapy warrants further studies.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.