Impact of immunochemotherapy administration sequence on overall survival in advanced esophageal and gastric cancers: a propensity score-matched multicenter analysis

Sep 22, 2026

Background: The optimal sequence for administering immune checkpoint inhibitors (ICIs) and chemotherapy in advanced esophageal and gastric cancers remains undefined, and overall survival (OS) is key for optimizing treatment. Methods: This multicenter study enrolled 334 advanced patients (Jan 2018–Oct 2024) and used propensity score matching (PSM) to create 292 matched cases comparing ICIs-first (IF) versus chemotherapy-first (CF). Results: OS was longer in CF after PSM and in the unmatched cohort; ECOG status, PD-L1, antibiotic use, and ICI line were independent factors. Conclusions: Chemotherapy before immunotherapy may improve OS, especially as first-line treatment.

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Abstract

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Cancer Immunology, Immunotherapy (2026) 75:136 [https://doi.org/10.1007/s00262-026-04382-3](https://doi.org/10.1007/s00262-026-04382-3) Impact of immunochemotherapy administration sequence on overall survival in advanced esophageal and gastric cancers: a propensity score‑matched multicenter analysis Junjie Hang1 · Lixia Wu2 · Li Xiao1 · Qiuhua Duan3,4 · Han Zhao1 · Junjie Huang5,6 · Jinfeng Guo1 · Yiqing Huang7 · Dapeng Zhang7 · Gang Cheng7 · Xiao Dong8 · Peng Xue8,9 · Jianhua Chang1 Received: 19 June 2025 / Accepted: 24 March 2026 © The Author(s) 2026 Abstract Background The optimal sequence of administering immune checkpoint inhibitors (ICIs) and chemotherapy in advanced esophageal cancer (EC) and gastric cancer (GC) remains to be established. Understanding how this sequencing affects overall survival (OS) is crucial for optimizing treatment strategies. Methods This multicenter study enrolled 334 patients diagnosed with advanced EC or GC between January 2018 and October 2024. To reduce confounding biases, propensity score matching (PSM) was applied, resulting in 292 matched patients categorized into two groups, including those receiving ICIs first (IF) and those receiving chemotherapy first (CF) . Results Following PSM, Kaplan–Meier analysis showed that the CF group had a significantly prolonged median OS compared to the IF group (16.80 vs. 14.60 months; p = 0.014) . These findings were further corroborated in the unmatched cohort (16.60 vs. 14.60 months; p = 0.012). Multivariable analysis identified ECOG performance status, PD-L1 expression, antibiotic use, and line of ICI treatment as independent prognostic factors, whereas the immunochemotherapy administration sequence did not retain independent prognostic significance. Subgroup analysis revealed that among patients receiving first-line immunochemotherapy, those in the CF group had significantly longer OS (16.50 vs. 12.30 months; p = 0.004), with no significant difference observed for those beyond first-line treatment (p = 0.862) . The objective response rate and disease control rate were comparable between the two groups. Conclusions This study suggests that administering chemotherapy prior to immunotherapy appears to improve OS in patients with advanced EC and GC, particularly when initiated as first-line treatment. These findings highlight the need for further research into biomarkers and personalized treatment strategies to enhance patient outcomes. Keywords Immunochemotherapy administration sequence · Overall survival · Esophageal cancers · Gastric cancers · Propensity score-matched analysis Introduction The introduction of immune checkpoint inhibitors (ICIs), particularly those targeting the programmed cell death protein 1 (PD-1) and its ligand PD-L1, has revolutionized cancer treatment by leveraging the host immune system to combat malignancies [1] . The PD-1/PD-L1 axis suppresses T cell activation by transmitting inhibitory signals upon binding, whereby blocking this interaction can restore Junjie Hang, Lixia Wu, Li Xiao and Qiuhua Duan have contributed equally to this work. Extended author information available on the last page of the article antitumor immunity and prevent T cell exhaustion [2] . For gastric cancer (GC) and esophageal cancer (EC), emerging evidence indicates that immunotherapy has become an integral component of standard treatment protocols. The Checkmate-649 trial demonstrated the efficacy of PD-1 inhibitors as a first-line treatment for advanced GC and EC, through the combined use of nivolumab and chemotherapy [3] . The median over survival (OS) for the nivolumab plus chemotherapy group was 13.1 months, which was significantly longer than the 11.1 months observed with chemotherapy alone. Subsequently, the KEYNOTE-811 trial investigated the effectiveness of first-line pembrolizumab in combination with trastuzumab and chemotherapy for HER2-positive advanced GC [4] . The KEYNOTE-590 trial further confirmed the super

FAQs

What clinical question does the study address?

It evaluates whether the order of giving immune checkpoint inhibitors and chemotherapy affects overall survival in advanced esophageal and gastric cancers.

How was patient selection and bias reduction handled?

The study enrolled 334 patients and applied propensity score matching (PSM), yielding 292 matched patients for the primary comparison.

What was the main survival finding between CF and IF groups?

After PSM, the chemotherapy-first (CF) group had a significantly prolonged median OS versus the ICIs-first (IF) group, and this result was also confirmed in the unmatched cohort.

Which factors were independent prognostic indicators?

Multivariable analysis identified ECOG performance status, PD-L1 expression, antibiotic use, and line of ICI treatment as independent prognostic factors, while the sequencing itself did not remain independently significant.

Sep 22, 2026

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