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Comparison of Efficacy of Aspirin Plus EOX vs. EOX Alone in Patients with Locally Advanced and Metastatic Gastric Cancer: a Randomized Clinical Trial

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Abstract

Purpose

The role of aspirin in cancer prevention has been well defined; the last decade revealed its therapeutic role with improved efficacy when aspirin was added to capecitabine in heavily pre-treated metastatic colorectal cancer. Aspirin affects tumour growth through the PI3K pathway, which regulates apoptosis and autophagy. The objective was to compare the efficacy of aspirin plus epirubicin, oxaliplatin, capecitabine (EOX) chemotherapy versus EOX alone in locally advanced and metastatic gastric cancer.

Methods

All patients with advanced gastric cancer reporting to the Department of Medical oncology between March 2017 and May 2019 were screened for study eligibility. They were randomly assigned to standard EOX with or without aspirin at a daily dose of 150 mg. Tumour measurements were assessed at baseline and after 3–4 cycles by an independent blinded radiologist according to RECIST criteria 1.1. Toxicity profiles were recorded as per CTCAE v 4.03. Per-protocol group was identified as 70 patients. The primary endpoint was overall response rates in the per-protocol group (defined as patients who received a minimum of 3 cycles and had an evaluable response after randomization). The secondary endpoints included toxicity analysis, progression-free survival, and overall survival.

Results

Ninety-five patients who fulfilled the study inclusion and exclusion criteria were randomized to group 1 EOX (50) or group 2 EOX plus aspirin (45). Seventy patients were included for the per-protocol analysis. The overall response rate in group 1 was 27% compared to group 2, which was 42%, P = 0.176. The median duration of follow was 29 (18.56–39.45) months. The median overall survival (n = 95) of group 1 versus group 2 was 11 (8.58–13.42) months and 10 (6.86–13.14) months, respectively, P = 0.90. There was no statistical significance in the overall survival per-protocol analysis (n = 70) between group one 12 (8.75–15.25) months versus group two 12 (6.21–17.79) months, P = 0.50.

Conclusions

There was no improvement in the response rates, progression-free survival, and overall survival on adding aspirin to EOX chemotherapy in locally advanced and metastatic gastric cancer in an unselected population. A further role of PI3K mutation as a biomarker needs to be evaluated in this setting.

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Data Availability

Data are available on request from the corresponding author.

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Funding

We thank JIPMER for assisting with financial support in the conduction of the study.

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Authors and Affiliations

  1. Department of Medical Oncology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India

    Esha Jafa, Charles L, Yadav Nisha, Smita Kayal, Prasanth Ganesan & Biswajit Dubashi

  2. Department of General Surgery, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India

    Vikram Kate

  3. Department of Pathology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India

    Rajesh Nachiappa Ganesh

  4. Department of Radio-Diagnosis, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India

    Sunitha V.C.

  5. Department of Surgical Oncology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India

    Prasanth Penumadu

Authors
  1. Esha Jafa
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  2. Charles L
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  3. Yadav Nisha
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  4. Vikram Kate
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  7. Sunitha V.C.
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  8. Prasanth Ganesan
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  10. Biswajit Dubashi
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Contributions

Esha Jafa: conception, design, data collection, first draft. Charles L: data collection, interpretation. Yadav Nisha: data analysis and interpretation, drafting the manuscript. Vikram Kate: supervision, revision for important intellectual content. Sunitha V.C.: response assessment, supervision, revision for important intellectual content. Smita Kayal: supervision, revision for important intellectual content. Rajesh Nachiappa Ganesh: response assessment, supervision, revision for important intellectual content. Prasanth Ganesan: supervision, revision for important intellectual content. Prasanth Penumadu: supervision, revision for important intellectual content. Biswajit Dubashi: conception, design, methodology, supervision, revision for important intellectual content. All authors have read and approved the final manuscript.

Corresponding author

Correspondence to Biswajit Dubashi.

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Ethics Approval

This study was approved by the Institute Ethics Committee. IEC approval no: JIP/IEC/2016/1069.

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Informed consent was obtained from the participant before enrollment into the study.

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Not applicable.

Competing Interests

The authors declare no competing interests.

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Jafa, E., L, C., Nisha, Y. et al. Comparison of Efficacy of Aspirin Plus EOX vs. EOX Alone in Patients with Locally Advanced and Metastatic Gastric Cancer: a Randomized Clinical Trial. J Gastrointest Canc 54, 642–650 (2023). https://doi.org/10.1007/s12029-022-00845-9

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  • DOI: https://doi.org/10.1007/s12029-022-00845-9

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