Does chemotherapy regimen matter for first-line immunochemotherapy in low PD-L1-expressing esophageal squamous cell carcinoma? A systemic review and meta-analysis

Abstract

Anti-PD-1 therapy plus chemotherapy (immunochemotherapy) has become standard first-line treatment for high PD-L1-expressing advanced esophageal squamous cell carcinoma (ESCC). Benefits of immunochemotherapy for low PD-L1-expressing ESCC remain debatable. The Cochrane, PubMed, and Embase databases were systemically searched from inception till 10 August 2024. Randomized trials comparing first-line immunochemotherapy with chemotherapy in ESCC were identified and evaluated association of platinum plus paclitaxel (TP) or fluoropyrimidine (PF) chemotherapy regimen, stratified by PD-L1 expression levels, with progression-free survival (PFS) and overall survival (OS) benefits. Pooled study-level hazard ratios (HRs) with 95% confidence intervals (CIs) for PFS and OS were calculated with a random-effects model. Eight studies involving 4733 participants were included. In high PD-L1 group, PFS (HR of TP: 0.56 [95% CI, 0.45-0.69] vs HR of PF: 0.53 [95% CI, 0.45-0.62]) and OS benefits (HR of TP: 0.60 [95% CI, 0.46-0.78] vs HR of PF: 0.59 [95% CI, 0.50-0.69]) did not significantly differ between two regimen subgroups (P = 0.75 and 0.90, respectively). In low PD-L1 group, TP regimen was associated with a significantly greater PFS benefit than PF regimen (HR of TP: 0.59 [95% CI, 0.48-0.74] vs HR of PF: 0.82 [95% CI, 0.72-0.94]; P = 0.01) and TP regimen trended to associate with greater OS benefit over PF regimen (HR of TP: 0.72 [95% CI, 0.55-0.93] vs HR of PF: 0.84 [95% CI, 0.72-0.97]; P = 0.32). In patients with low PD-L1-expressing advanced ESCC, immunochemotherapy with TP may confer a greater PFS benefit than that with PF.

Keywords: Chemotherapy; Esophageal squamous cell carcinoma; Immune checkpoint inhibitor; PD-L1 expression.

Fig. 1

Forest plots from the meta-analysis illustrating the comparison of progression-free survival (PFS) (a) and overall survival (OS) (b) between anti-PD-1/PD-L1 therapy combined with chemotherapy and chemotherapy alone

Fig. 2

Forest plots from the meta-analysis illustrating progression-free survival (PFS) (a) and overall survival (OS) (b) in a comparison of anti-PD-1/PD-L1 therapy combined with chemotherapy and chemotherapy alone, stratified by PD-L1 expression level (high PD-L1 expression: CPS ≥ 10, TAP ≥ 10, or TPS ≥ 1; low PD-L1 expression: CPS < 10, TAP < 10, or TPS < 1)

Fig. 3

Meta-analysis forest plots for progression-free survival (PFS) (a) and overall survival (OS) (b) in a comparison of anti-PD-1/PD-L1 therapy combined with chemotherapy and chemotherapy alone, stratified by chemotherapy regimen (PF fluoropyrimidine plus platinum, TP paclitaxel plus platinum)

Fig. 4

Meta-analysis forest plots for progression-free survival (PFS) and overall survival (OS) for patients receiving anti-PD-1/PD-L1 therapy combined with chemotherapy versus chemotherapy alone, stratified by PD-L1 expression level (high PD-L1 expression: CPS ≥ 10, TAP ≥ 10, or TPS ≥ 1; low PD-L1 expression: CPS < 10, TAP < 10, or TPS < 1) and chemotherapy regimen (PF fluoropyrimidine plus platinum, TP paclitaxel plus platinum) in the high PD-L1 expression (a and b) and low PD-L1 expression subgroups (c and d)

Fig. 5

Network meta-analysis forest plots depicting progression-free survival (PFS) and overall survival (OS) in a comparison of anti-PD-1/PD-L1 therapy combined with paclitaxel plus platinum (TP) or fluoropyrimidine plus platinum (PF) in patients with high (a–c) and low (d–f) PD-L1 expression