Pembrolizumab in Gastric Cancer Shows Surprising Updated Findings

Updated findings from the KEYNOTE-012 trial have demonstrated promising antitumor activity with pembrolizumab (Keytruda) in patients with metastatic gastric cancer.

Yung-Jue Bang, MD, PhD

Updated findings from the KEYNOTE-012 trial have demonstrated promising antitumor activity with pembrolizumab (Keytruda) in patients with metastatic gastric cancer.

“We knew that immunotherapy was effective in patients with melanoma. Recently, immune checkpoint inhibitors were also found to be effective in small-cell lung cancer. However, we did not expect such activity in patients with advanced gastric cancer, because we did not believe the cancer was immunogenic,” said the trial’s lead investigator Yung-Jue Bang, MD, PhD, professor of medical oncology, Seoul National University College of Medicine, president, Biomedical Research Institute, Seoul National University Hospital, in an interview withTargeted Oncology.

The anti—PD-1 monoclonal antibody was investigated as part of the gastric cancer cohort of KEYNOTE-012, which included 39 patients whose tumors expressed programmed death-ligand 1 (PD-L1). The study is ongoing, and participants in the cohort are receiving IV pembrolizumab at 10 mg/kg once every 2 weeks, and will continue to receive the drug until disease progression, death, withdrawal of consent, or until patients have been on treatment for 2 years.

“In this study, some patients had durable efficacy. It is quite exciting and promising. It is possible that gastric cancer treatment may be designed with more of a targeted therapy approach in the future,” Yung-Jue Bang said.

Thus far, approximately 53% of patients have had some degree of tumor shrinkage. The overall response rate for patients receiving pembrolizumab is 22.2% (95% CI, 10.1-39.2) by RECIST v.1 central review and 33.3% (95% CI, 19.1-50.2) by investigator review. There were eight partial responses and stable disease was observed in another five patients.

“These results are quite promising; they have led to a number of other trials that we are awaiting results on,” said Yung-Jue Bang. “The study also suggests that a particular immune gene signature can predict which patients will respond to this class of agents. More data is needed to validate these findings, but it is promising at this time. In patients with melanoma, it was shown that this kind of gene signature could predict the benefit of anti—PD-1 agents. Moreover, we had similar findings in our gastric cancer cohort, so it is worth investigating further.”

Although Yung-Jue Bang expressed excitement regarding these findings, the challenge may now involve finding the right patient to study in clinical trials based on this kind of gene signature.“In the future, I think we will find a better way to find the best patients for this class of agents,” he said.

He also thinks that combination treatment should absolutely be considered. “Pembrolizumab or another similar agent could be combined with a variety of agents, including other immune checkpoint agents, chemotherapy, or targeted therapy. That is the future of this therapy,” he said.

Yung-Jue Bang advises caution with combining pembrolizumab with ipilimumab because of potential increases in adverse events.

He predicts that immunotherapy may have potential in earlier treatment settings in gastric cancer as well.“There is some testing that has just started with immunotherapies in the first-line setting. I think this will continue. Immunotherapy agents have the potential to benefit many, many patients in multiple settings in the future.”