Mismatch repair deficiency limits chemo response in gastric cancer

Last Updated: 2017-03-01

By David Douglas

NEW YORK (Reuters Health) - Patients with gastroesophageal cancer with mismatch repair deficiency (MMRD) and microsatellite instability (MS) may not benefit from perioperative chemotherapy, according to a secondary analysis of a clinical trial.

"Patients with gastroesophageal cancer are often treated with perioperative chemotherapy which helps to improve their survival compared to surgery alone,” Dr. Elizabeth C. Smyth of the Royal Marsden Hospital, London told Reuters Health by email.

“However," she said, "not all patients benefit from this approach, which is also associated with side effects such as nausea and vomiting, and the risk of neutropenic infection."

Currently, patient selection for neoadjuvant or perioperative chemotherapy is based purely on preoperative radiologic staging, she and her colleagues note in a February 23 online paper in JAMA Oncology.

MMRD, which is seen in up to 22% of stomach cancers, and MSI are prognostic for survival in many cancers and the team sought to further define their role using data from the MAGIC trial involving participants who were treated with surgery alone or with chemotherapy.

MSI results were available in 303 participants. Of these, 283 had microsatellite stability or low MSI and 20 had high MSI. MSI and MMR status were available in a total of 254 patients.

Compared to patients with MS stability or low MSI, or with MMR-proficient tumors, patients with high MSI or MMRD tumors had superior survival when treated with surgery alone but inferior survival when treated with perioperative chemotherapy plus surgery.

Specifically, patients treated with chemotherapy plus surgery who had either high MSI or MMRD had a median overall survival of 9.6 months, compared to 19.5 months for those without high MSI or MMRD.

Among patients treated with surgery alone, the median OS was not reached in those with high MSI or MMRD but was 20.5 months in those without high MSI or MMRD.

The researchers concede that among limitations of the study is that the entire MAGIC cohort was not analyzed because of a lack of tissue samples. Also, the "low prevalence of MSI and MMRD and the number of events limit the statistical reliability of these data."

Still, Dr. Smyth said, "while patients with MMRD tumors have excellent survival when treated with surgery alone, when chemotherapy was added to surgery these patients appeared to have worse survival."

"This is a relatively small dataset, and therefore these results cannot be considered practice changing,” she said. “However, as immuno-oncology drugs have been associated with excellent results in patients with advanced or metastatic MMRD cancers, it is possible that exploration of these compounds in operable MMRD gastric cancer could be beneficial in future."

SOURCE: http://bit.ly/2lcOzZp

JAMA Oncology 2017.