# Immunotherapy in advanced esophageal squamous cell cancer: earlier or later?

## TL;DR

This study compares the effectiveness of early versus late immunotherapy in advanced esophageal cancer, finding that early use improves progression-free survival but not overall survival.

## Contribution

The study provides new insights into the optimal timing of immunotherapy for esophageal squamous cell cancer.

## Key findings

- Early immunotherapy improved progression-free survival (PFS1) but not overall survival (OS) in patients with advanced ESCC.
- Subgroup analysis identified specific patient characteristics associated with greater benefits from early immunotherapy.
- Multivariate analysis showed that early immunotherapy and tumor differentiation impacted OS.

## Abstract

Several large-scale phase III clinical trials have confirmed the survival benefit of immunotherapy in patients with locally advanced or metastatic esophageal cancer (EC). The study aimed to investigate whether early use of immunotherapy can improve long-term survival.

Patients with locally advanced or metastatic esophageal squamous cell cancer (ESCC) diagnosed from January 2018 to December 2021 were retrospectively analyzed. According to the time of immunotherapy, patients were divided into the early immunotherapy group (EIT group, first-line immunotherapy) and the late immunotherapy group (LIT group, second-line immunotherapy). A 1:1 propensity score matching (PSM) was applied to balance the observable potential confounding factors between the two groups. The primary outcome was overall survival (OS).

A total of 359 patients were enrolled; after propensity score matching, the clinical features were well balanced between the two groups, including 107 patients. The median OS was 15.7 months (95%CI: 12.81–18.59) in the EIT group and 17.7 months (95%CI: 14.89–20.57) in the LIT group, respectively (p = 0.185, HR = 1.25). The PFS1 of patients was 8.7 months (95%CI: 7.53–9.87) and 7.6 months (95%CI: 5.90–9.30), respectively, and the difference was statistically significant (p = 0.032, HR = 0.72). The PFS2 of patients was 12.97 months (95%CI: 11.37–14.58) and 12.93 months (95%CI: 11.65–14.21), respectively, and the difference was statistically significant (p = 0.045, HR = 0.73). Subgroup analysis showed that male patients with middle thoracic EC, younger than 65 years old, with only one site of metastasis, only lymph node progression, no combined radiotherapy after progression, and TP (paclitaxel + platinum) regimen chemotherapy may have greater benefits. The COX multivariate analysis showed that the EIT group and the differentiation degree of the tumor had an impact on OS (P: 0.03, 0.04; HR: 0.73, 0.70).

Early immunotherapy can improve PFS without affecting OS for patients with locally advanced or metastatic ESCC.