Dr. Chao on the Utility of MSI as a Biomarker in Gastric/GEJ Cancer

Joseph Chao, MD, assistant clinical professor, Department of Medical Oncology and Therapeutics Research, City of Hope, discusses the utility of microsatellite instability (MSI) status as a prognostic biomarker in gastric and gastroesophageal junction (GEJ) cancer.

Typically, patients with stage IV gastric/GEJ cancer have a relatively poor prognosis, says Chao. However, MSI—high (MSI-H) patients have improved outcomes with PD-1 inhibitors.

In September 2017, the FDA approved the PD-1 inhibitor pembrolizumab (Keytruda) for the treatment patients with PD-L1—positive recurrent or advanced gastric/GEJ adenocarcinoma who have received ≥2 prior lines of therapy.

A comparative analysis of the phase II KEYNOTE-059 and phase III KEYNOTE-061 and KEYNOTE-062 trials indicated that pembrolizumab monotherapy elicited clinically meaningful efficacy and more durable responses compared with chemotherapy in patients with a combined positive score ≥10 in the first-, second-, and third-line settings.

In Japan, regulatory authorities approved nivolumab (Opdivo) for patients with gastric/GEJ cancer regardless of biomarker status. However, MSI-H patients who receive nivolumab derive favorable outcomes compared with patients with microsatellite stable disease, concludes Chao.