Comparison of efficacy of Aspirin plus EOX vs. EOX alone in patients with locally advanced and metastatic gastric cancer: a randomized clinical trial

Abstract

Introduction: The role of aspirin in cancer prevention has been well defined; the last decade revealed its therapeutic role with Giampieri et al. (2016) showed improved efficacy with aspirin 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 of our study was to compare the efficacy of Aspirin plus 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 to 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. Tumor measurements were assessed at baseline and 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 group1 EOX (50) or group 2 EOX plus Aspirin(45). Seventy patients were included for the per-protocol analysis. The overall response rate in group1 was 27% compared to group2, 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.

Aspirin and cancer: biological mechanisms and clinical outcomes

“…During a median follow-up of 20 months 191 invasive events had occurred (84 on aspirin 107 on placebo 84: HR 1.27) [48]. Even more recently 95 patients with locally advanced metastatic gastric cancer were randomized, 45 to receive 150 mg aspirin daily, 45 to receive no aspirin [49]. After a median follow-up of 29 months the median survival of patients on aspirin was 10 months compared with 11 months in patients who received no aspirin ( p = 0.90).…”