ESMO WCGIC 2023 | KEYNOTE-859: pembrolizumab plus chemotherapy in G/GEJ adenocarcinoma

So KEYNOTE-859 is a global study of the metastatic and advanced gastric cancer where the patients, regardless of their PD-L1 status, were treated with pembrolizumab or placebo combined with standard chemotherapy. This study enrolled nearly 1500 of the HER2 negative gastric cancer patients in a true global manner. One third of the patients were coming from Asia. One quarter of the patients were from the Western Europe and North America and 40% of the patients were coming from the rest of the world.

In this study, the primary outcome was overall survival, which fortunately was met in all subgroups, including intention to treat population which consisted of the patients regardless the PD-L1 status, which is very positive and it was also positive in the patients with PD-L1 score over one which contributed to 78% roughly of the study population a completely not expected. It was also positive in the previously well known population of over ten. So summarizing this study, this is a positive study in terms of the primary outcomes. What we learned today is that among the other other outcomes we reported the so-called PFS2. PFS2 is a time to progression on the subsequent treatments, which was the time to the progression or death due to any reason. And here we have shown that the outcomes for PFS2 are consistent with PFS. What means that the there is no negative selection of the outcomes in the patients who are pre-exposed to immunotherapy, which is very positive, which probably will translate that in further follow up. The overall survival will not be negative in the in the further observation.

We also reported the subsequent therapies in this huge cohort of nearly 1500 patients, which shows the real world evidence how we are treating the gastric cancer currently. So 40% of the patients is receiving chemotherapy, second line chemotherapy in this population and in both arms meaning the previously treated with and without exposure less than 9% receives the immunocompetent drugs. So this is the setting and we have shown that it’s balanced, meaning that there was no preselection bias. So summarizing this is an important global study which confirms that there is a role of immuno oncology agents in the treatment of advanced gastric cancer.

During the oral session, Florian Lordick, who was commenting it just after the release has noticed many strong points of that study although this there was also a comment that in the patient populations with the biomarker of CPS between 1 and 9 the results may not be so so strong to to suggest that all the patients in this group should be treated like this. This is important to notice that this subgroup of CPS between 1 and 9 is about 40% of our HER2-negative population, which which is very important part of the of the population in this study. It was not designed to report these outcomes. So this is rather exploratory analysis. So I would not stress that it should be assessed with very, very strong outcomes that that this population should be treated carefully with with. I’ll there is one very important point, which is the technical aspect of assessing CPS. We are all aware that this is not a perfect marker, that sometimes the assessment if the patient is CPS one or 5 or 9 is tricky and having a strict comment that patient with CPS between 1 and 9 should not be treated with the with the eye or should be treated carefully is in my opinion not supported. We have shown that also intention to treat population gives the gives the positive. If outcomes which means that all comers which means that you don’t need to pre-select the patients so it’s very democratic way of of treatment.