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Abstract
Background Emerging evidence of immunotherapy demonstrated tumor regression for locally advanced resectable esophageal cancer in the neoadjuvant setting; however, its long-term clinical outcomes analysis and systematical comparison with current standard-of-care therapy remain to be investigated.
Methods In this systematic review and meta-analysis, we searched PubMed, Embase, Cochrane Library, ClinicalTrials.gov, Web of Science, and, other literature sources for controlled trials and cohort studies published in English from inception to February 23, 2024 (IDDF2024-ABS-0382 Figure 1. Flowchart following the PRISMA guidelines). Eligible trials evaluated at least one immune checkpoint inhibitor in the experimental group versus chemoradiotherapy or chemotherapy alone in the control group, or a comparison of the two chemotherapy regimens. The primary outcome was overall survival (OS) presenting as pooled hazard ratios (HR) and secondary outcomes were estimated as odds ratios (OR), through common-effects or random-effects model. This study is registered with the Open Science Framework, DOI osf.io/f64xc, and PROSPERO, CRD42024489145.
Results The meta-analysis comprised 36 studies (10576 patients) enrolled. Median follow-up was 2?8 years [95% CI 2·6–3·6]. OS following neoadjuvant immunotherapy was longer than following chemoradiotherapy or chemotherapy alone (HR 0·57 [95% CI 0·42–0·78]; 7 studies; 1137 patients), with no significant differences between the two chemotherapy regimes in OS (HR 1·00 [95% CI 0·91–1·10]; 8 studies; 3555 patients) (IDDF2024-ABS-0382 Figure 2. These studies reported propensity score-matched data). Neoadjuvant immunotherapy with grade 3 or more adverse events higher than chemotherapy alone (OR 1·17 [95% CI 0·84–1·62]; 3 studies; 669 patients) but lower than chemoradiotherapy (OR 0·71 [95% CI 0·49–1·01], 3 studies; 358 patients), which like pCR rate. The trial-level correlation between pCR rate with OS was weak (R2=0·07 [95% CI 0·00-0·29]; 17 studies,6238 patients), irrespective of neoadjuvant therapy (IDDF2024-ABS-0382 Figure 3. Trial-level correlation of pCR with OS).
Flowchart following the PRISMA guidelines
These studies reported propensity score-matched data
Trial-level correlation of pCR with OS
Conclusions Neoadjuvant immunotherapy in the neoadjuvant setting may be superior to standard-of-care therapy for patients with resectable esophageal cancer.