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.

Videos

Joseph Chao, MD, discusses the utility of microsatellite instability (MSI) status as a prognostic biomarker in gastric and gastroesophageal cancer.

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 practice-changing data in metastatic gastroesophageal (GEJ) cancer.

Based on the results of the phase III TAGS trial presented at the 2018 ESMO Congress, TAS-102 (trifluridine/tipiracil; FTD/TPI; Lonsurf) was shown to be safe and effective in patients with refractory metastatic GEJ cancer. The combination showed a statistically significant improvement in median overall survival (OS) and progression-free survival (PFS), irrespective of prior gastrectomy, compared with best supportive care and placebo, says Chao. Patients who received TAS-102 experienced a median OS of 5.7 versus 3.6 months in those who received placebo. The rates of median PFS with TAS-102 and placebo were 2.0 and 1.8 months, respectively.

Patients enrolled in the study had to have received at least 2 prior lines of therapy, but many patients had progressed on as many as 4 lines of therapy, explains Chao. Although response rates were modest, many patients achieved disease control.

Joseph Chao, MD

Articles

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

Dr. Chao on Practice-Changing Data in Metastatic Gastroesophageal Cancer