Pembrolizumab Effective Treatment Option for MSI-H Gastric Cancer

Kohei Shitara, MD, Department of Gastrointestinal Oncology, National Cancer Center Hospital East, Japan, discusses the KEYNOTE-062 trial of pembrolizumab with or without chemotherapy in patients with advanced gastric cancer, including a subgroup analysis for patients with microsatellite instability–high (MSI-H) disease, at the ESMO 2019 Congress.

Transcript

Hi. My name is Kohei Shitara. I'm a GI medical oncologist from National Cancer Center Hospital East in Japan. In this ESMO meeting, we represent our results from the KEYNOTE-062 trial, which investigated pembrolizumab as first-line treatment for gastric cancer and subgroup analysis, especially for MSI-high patients.

Pembrolizumab is already approved for PD-1 positive, combined positive score (CPS) 1 or higher population, as second-line or regular line treatment by FDA. Pembrolizumab also received accelerated FDA approval for previously treated MSI-high tumors.

In this KEYNOTE-062 trial, eligible patients were HER2 negative and PD-1 positive with CPS 1 or higher population. The patients were randomized to 3 arms with pembrolizumab monotherapy, pembrolizumab plus chemotherapy, and chemotherapy.

In this trial, primary analysis was already presented in previous ASCO and ESMO GI. In this trial, the pembrolizumab monotherapy showed noninferiority in overall survival. In patients with higher PD-L1 expression, defined as a CPS 10 or higher population, also showed the trend of improvement of overall survival, but this was not actually tested in primary analysis.

In this ESMO meeting, we presented the subgroup analysis for MSI-high tumors. Approximately a total of 50 patients were included in here. There are approximately 60% of patients who had CPS 10 or higher scores.

Patients who received the pembrolizumab monotherapy showed clearly better outcome compared with the chemotherapy, hazard ratio of .29. 2-year survival rates were 71% with pembrolizumab monotherapy and 26% with chemotherapy, a remarkable difference.

Patients who received pembrolizumab plus chemotherapy did not show any improvement in overall survival in overall patient population, but in this subgroup analysis, chemotherapy plus pembrolizumab also showed a good outcome in MSI-high patients, hazard ratio of .37, in MSI-high patients who received pembrolizumab plus chemotherapy, compared with chemotherapy.

Response rates were also higher in pembrolizumab monotherapy, or pembrolizumab plus chemotherapy, than chemotherapy alone. The response rate was 65% with chemotherapy plus pembrolizumab, and 57% for pembrolizumab monotherapy, and 37% for chemotherapy, so more than 20% difference.

PFS also show the trend of improvement with pembrolizumab therapy or pembrolizumab plus chemotherapy.

Overall, this trial suggested the clear activity of pembrolizumab therapy or combination for MSI tumor.

Most important, the conclusion here is patient should know MSI status before first line treatment and if you are available, pembrolizumab combined treatment might be a treatment option for such patients.