Efficacy and safety of sequential immunotherapy following concurrent radiotherapy with S-1 in older patients with esophageal squamous cell carcinoma: an inverse probability weighting analysis

TL;DR

Adding immunotherapy after radiotherapy and chemotherapy may improve outcomes for older patients with esophageal cancer, but requires monitoring for side effects.

Contribution

This study evaluates the safety and efficacy of sequential immunotherapy after CCRT in older ESCC patients using IPTW analysis.

Findings

Sequential ICIs after CCRT significantly improved progression-free survival in older ESCC patients.

Immunotherapy increased risks of pneumonitis and hypothyroidism but reduced neutropenia and vomiting.

Age ≥75, ECOG score 2, T4, and N3 stages were identified as adverse prognostic factors.

Abstract

To evaluate the efficacy and safety of sequential immune checkpoint inhibitors (ICIs) following concurrent chemoradiotherapy (CCRT) in older (≥70 years) patients with locally advanced esophageal squamous cell carcinoma (ESCC).

A total of 193 older patients (≥70 years) with locally advanced ESCC treated between January 2022 and December 2023 were retrospectively analyzed and divided into two groups: the CCRT group (radiotherapy with concurrent S-1, n=108) and the CCRT+ICIs group (sequential ICIs after CCRT, n=85). Baseline imbalances were adjusted via inverse probability of treatment weighting (IPTW). The primary endpoints were overall survival (OS) and progression-free survival (PFS), whereas the secondary endpoints included safety and prognostic factors.

After IPTW adjustment, OS in the CCRT+ICIs group tended to improve compared with that in the CCRT alone group (HR = 0.70, 95% CI: 0.48–1.04, p=0.071), although the difference was not statistically significant. In contrast, PFS was significantly improved in the CCRT+ICIs group (HR = 0.59, 95% CI: 0.42–0.84, p=0.003). Multivariate analysis identified age ≥75 years (OS: HR = 1.893; PFS: HR = 2.097), ECOG score =2 (OS: HR = 3.310; PFS: HR = 2.188), T4 stage (OS: HR = 2.221; PFS: HR = 2.080), and N3 stage (OS: HR = 3.841; PFS: HR = 2.920) as independent adverse prognostic factors. Immunotherapy-specific toxicities, including hypothyroidism and pneumonitis, occurred more frequently in the CCRT+ICIs group, which is consistent with the toxicity profile of ICIs, whereas neutropenia and vomiting were less common. A lower incidence of vomiting was also observed in the CCRT+ICIs group, although the difference did not reach statistical significance (p=0.053).

Sequential ICI therapy after CCRT significantly improved PFS and reduced mortality risk in older ESCC patients, though close monitoring is warranted for pneumonitis and skin-related toxicities. The reduced incidence of neutropenia suggests a hematologic safety advantage of the sequential strategy. Patients aged ≥75 years, with an Eastern Cooperative Oncology Group (ECOG) score of 2, or with N3 disease constitute high-risk subgroups and warrant individualized treatment approaches.

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