ICI timing did not change pathological response when neoadjuvant ESCC backbones were matched

KEY POINTS

• The systematic review and meta-analysis included 53 prospective studies and 2,937 patients with non-metastatic resectable esophageal squamous cell carcinoma receiving neoadjuvant PD-1 inhibition with chemotherapy or chemoradiotherapy.
• The evidence was heavily imbalanced by strategy: 48 studies used concurrent ICI, four used consolidation ICI after cytotoxic treatment, and only one investigated induction followed by concurrent ICI. Among surgical patients, there were 2,238 concurrent versus only 108 consolidation cases.
• When all treatment backbones were pooled, consolidation ICI appeared substantially better: pathological complete response was 48% versus 31% with concurrent ICI (p=0.0005).
• That advantage disappeared when the comparison was restricted to studies in which both groups received chemoradiotherapy. Pathological complete response was then 48% with consolidation versus 41% with concurrent ICI (p=0.18).
• The same pattern appeared for major pathological response. Across all studies it was 76% versus 57% (p=0.0116) in favor of consolidation, but with chemoradiotherapy in both groups the difference narrowed to 76% versus 70% (p=0.27).
• The result suggests an important confounder: sequential studies disproportionately used chemoradiotherapy, whereas many concurrent studies used chemotherapy without RT. The apparent sequencing effect therefore largely reflected the treatment backbone rather than ICI timing itself.
• Evidence remains insufficient for survival or toxicity comparisons. Only four consolidation studies were available, two were conference abstracts, almost all studies came from China, all used PD-1 inhibitors, and OS, DFS and safety data were too heterogeneous for meaningful quantitative synthesis.

CLINICAL TAKEAWAY

SOURCE

Clinical and Translational Radiation Oncology