Background and importance ESCORT-1st trial reported a benefit for overall survival (OS) of camrelizumab plus chemotherapy (Cam+CT) combination over chemotherapy (CT) in September 2021. Regimens with platinum agents have been the standard first-line treatment for advanced or metastatic oesophageal squamous cell carcinoma (mESCC) for decades.
Aim and objectives To develop a network meta-analysis (NMA) to provide an efficacy comparison of treatments for untreated patients with mESCC.
Material and methods A review in Pubmed and UpToDate databases was conducted on 3 October 2021. Inclusion criteria: randomised clinical trials (RCTs) including immune checkpoint inhibitor therapies (camrelizumab, pembrolizumab, nivolumab and ipilimumab) as first-line treatment of mESCC. Exclusion criteria: RCTs without a common comparator linking cited drugs. Efficacy endpoint was OS. NMA used combined direct and indirect evidence to estimate pooled hazard ratios (HR) by Bayesian methods. Fixed and random effects were considered. Deviance information criteria (DIC) statistics were evaluated to compare models. I2 determined the proportion of variability in outcomes due to heterogeneity.
Results Three RCTs were selected. The RCTs assessed the following regimens: Cam+CT, nivolumab plus ipilimumab (N+I), nivolumab plus chemotherapy (N+CT), pembrolizumab plus chemotherapy (Pem+CT) and CT. The common comparator was CT. Two RCTs included patients with 0–1 performance status (ECOG). Cam+CT study evaluated patients with a life expectancy of at least 12 weeks. Results of N+I and N+CT were obtained from a congress abstract. Similar values of DIC (difference <5, no minimun relevance) were estimated for fixed- and random-effects models. Fixed-effects model was selected due to the higher precision of data. I2 was 25%. Regarding Cam+CT (therapy with the greatest magnitude of effect), HR for OS were: 1.0 (95% CI 0.76 to 1.4) vs Pem+CT, 1.1 (95% CI 0.78 to 1.4) vs N+CT, 1.1 (95% CI 0.81 to 1.5) vs N+I and 1.4 (95% CI 1.1 to 1.8) vs CT. No statistically significant differences were found among Cam+CT, Pem+CT, N+CT and N+I. All schemes with immune checkpoint inhibitor drugs were superior to CT.
Conclusion and relevance This updated NMA showed a greater efficacy benefit of combinations with immunotherapeutic agents over CT in untreated patients with mESCC. Standard first-line therapy could be modified. Safety and efficiency criteria should also be considered in the therapeutic positioning of drugs in this clinical context.
References and/or acknowledgements None
Conflict of interest No conflict of interest