The KEYNOTE-062 study is an international multicentre phase III study that evaluates the role of pembrolizumab in the treatment of patients in the first line setting with advanced or metastatic gastric or gastroesophageal junction cancer that are PD-L1 positive and are HER2 negative. The patients were stratified by the geographical region, by the extent of the disease and by the fluoropyrimidine that they received. So basically the study had three arms, the first experimental arm was pembrolizumab as a single agent; the second arm was pembrolizumab combined with cisplatin and either 5-fluorouracil or capecitabine and the third arm, the control arm, was conventional chemotherapy with placebo.
The primary endpoints of the study were overall survival and progression free survival and secondary endpoints included safety and overall response rate. Patients, as in all clinical trials, were treated until progression of the disease, unacceptable toxicity or withdrawal of consent.
What were your main findings?
Globally we did two kinds of analysis basically comparing the pembrolizumab arm as a single treatment with chemotherapy and the second one was a combination of pembrolizumab plus chemotherapy versus chemotherapy. Moving to the first combination, pembrolizumab versus chemotherapy, the study met the primary endpoint of non-inferiority for overall survival favouring pembrolizumab, meaning that pembrolizumab is not inferior to chemotherapy. Nevertheless, we looked also at the population of patients that have CPS more than ten but in this population of patients although the benefits seemed to be higher we couldn’t do a formal statistical analysis because of the design of the study.
For the second comparison, the comparison of pembrolizumab plus chemotherapy versus chemotherapy the study did not meet the primary endpoint, meaning that the combination of pembrolizumab plus chemotherapy was not statistically significantly superior to chemotherapy alone although there was a suggestion for a benefit in the survival of these patients.
The other important data is the safety profile. So if we compare the population of patients that received pembrolizumab to those that received chemotherapy those patients receiving pembrolizumab had a better safety profile with less treatment related adverse events all grades and also grade 3-5 and less discontinuations.
What would be the clinical impact of these results?
The clinical impact of these results basically show that pembrolizumab in a selected population of patients with advanced or metastatic gastric and gastroesophageal junction cancer with PD-L1 expression, PD-L1 positive, show a benefit for pembrolizumab compared with chemotherapy. This could be an alternative treatment option.