MSI, MMRD Biomarkers Might Guide Gastro-Oesophageal Cancer Periop Chemotherapy Use

Perioperative chemotherapy benefit in gastro-oesophageal cancer may vary with microsatellite instability and mismatch repair deficiency status

medwireNews: Examining for microsatellite instability (MSI) and mismatch repair deficiency (MMRD) could help identify which gastro-oesophageal cancer patients will benefit from perioperative chemotherapy, research suggests.

“Because MSI or MMRD tumors comprise up to 10% to 20% of stomach cancers in some series, this finding has the potential to affect large numbers of patients”, the study authors believe. 

The secondary post hoc analysis of the MAGIC (Medical Research Council Adjuvant Gastric Infusional Chemotherapy) trial included MSI data for 303 participants who were treated for operable gastro-oesophageal cancer with surgery alone or alongside epirubicin, cisplatin and fluorouracil chemotherapy.

The original trial findings showed that 5-year overall survival (OS) was significantly longer in the patients given combined therapy, explain David Cunningham, from the Royal Marsden Hospital in London, UK, and co-authors in JAMA Oncology.

In all, 283 patients had tumours which showed microsatellite stability or low MSI, while 20 patients had high MSI, they report. And for the 254 patients with MMR results available for the proteins mutL homologue 1, mutS homologue 2, mutS homologue 6 and PMS1 homologue 2, concordance between high MSI and MMRD status was 97.6%.

Among the patients treated with surgery alone, median OS was not reached in the patients with high MSI or MMRD versus a median of 20.5 months for the patients who had neither biomarker, giving a nonsignificant hazard ratio (HR) of 0.42.

For patients who had received perioperative chemotherapy, however, median OS was significantly shorter for those with high MSI or MMRD than those without, at 9.6 versus 19.5 months and a HR of 2.18.

“If validated, this finding has the potential to improve patient selection for perioperative chemotherapy and spare a significant proportion of patients with gastric cancer unnecessary treatment”, the MAGIC investigators say. 

“We do not believe that these data justify a change in clinical practice; however, we recommend prospective trial validation to ascertain the optimal perioperative treatment for patients with [high MSI] gastric cancer.”

And they add: “In light of the remarkable success of anti–programmed cell death protein 1 therapies in MMRD colorectal cancer, alternative treatment strategies could be reasonably investigated for these patients.”


Symth EC, Wotherspoon A, Peckitt C, et al. Mismatch repair deficiency, microsatellite instability, and survival. An exploratory analysis of the Medical Research Council Adjuvant Gastric Infusional Chemotherapy (MAGIC) trial. JAMA Oncol 2017; Advance online publication 23 February. doi:10.1001/jamaoncol.2016.6762

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