Continued Benefit From Pembrolizumab Plus Chemotherapy in Later-Line Therapy for Patients With Advanced, HER2-Negative Gastric/Gastroesophageal Junction Adenocarcinoma

Additional Data from KEYNOTE-859

At the 2023 World Congress on Gastrointestinal Cancers, Lucjan Wyrwicz, MD, Maria Sklodowska Curie National Cancer Research Institute, Warsaw, Poland, presented additional data from KEYNOTE-859 evaluating the influence of subsequent therapies on outcomes for patients with advanced HER2-negative, gastric or gastroesophageal junction adenocarcinoma.

Dr Wyrwicz explained that the additional data further supports the use of pembrolizumab plus chemotherapy as a new first-line option for patients in this population.

Transcript:

Hello. My name is Lucjan Wyrwicz. I'm medical and radiation oncologist from Maria Curie National Cancer Research Institute in Warsaw, Poland. I'm here at the 2023 World Congress on GI Cancers in Barcelona, and I would like to give you the introduction about our research, which we have shown earlier today.

The KEYNOTE-859 is a global study, which covered patients with advanced and metastatic gastric and gastroesophageal junction cancers in the first line of treatment. This study was aimed to enroll 1,500 patients with HER2-negative gastric cancer regardless their PD-L1 status. Their PD-L1 status was supposed to be accessible, which means that the tissue was provided and was confirmed that we have all the data. This is very important aspect of the study since I will discuss the outcomes by the groups of PD-L1 status.

The primary outcome of this study was overall survival in intention-to-treat (ITT) populations, which means, in general, all-comers with additional outcomes pre-specified by the PD-L1 expression, the progression-free survival (PFS), the objective response rates and, of course, toxicity.

Coming through the data, it's completely clear that, in this study, we were able to show the positive outcomes in ITT population as well as in the population with the PD-L1 combined positive score (CPS) >1 and PD-L1 CPS >10. We also observed the enrichment in benefits when the PD-L1 status went into higher values. It seems to be taken for a while about epidemiology that, in this study, 78% of the patients has exhibited the PD-L1 expression, which still means the vast majority of this population of the patients. Also, PFS data were quite consistent with what was expected. We observed the prolongation with clinically significant P-values and hazard ratios, which were, of course, higher in patients with higher PD-L1 population.

When we discussed the toxicities, this is completely clear that this treatment is quite well-tolerated. There was a single patient in each arm, which consisted of more than 700 patients, or a single patient in 700 which had toxic death due to the treatment. Of course, grade 3/4 toxicities were observed, but these numbers were as it was expected. This study has not shown any unexpected toxicity of added pembrolizumab to standard chemotherapy, which was capecitabine-oxaliplatin or cisplatin-fluorouracil.

The duration of response was prolonged with combination of chemotherapy and pembrolizumab, as well as increased objective response rates. In this study, in the chemotherapy arm, the objective response rates for chemotherapy only were 43%, while in the pre-specified population of the patients with PD-L1 >1 ORR was around 60%. The clinically relevant deepness of response was proved and shown in this combination.

Here, we also reported the so-called PFS-2, which means the progression on the further-line of treatment or death to any reason. And this analysis has shown the significant prolongation with hazard ratio of 0.76, which was very similar to what we have shown with the general progression-free survival. The meaning of that is the disease progression is delayed by the same timeframe when we look at the end of the pembrolizumab treatment and the end of the next subsequent treatment, which means that there is no negative selection of cancer biology by the exposure to immuno-oncology agent. This is very important outcome.

Also, we reported today the treatments in post-progression on the first line of the treatment. In this study, we have shown that it's completely balanced. About 42% of the patient received the second line of treatment, and we need to consider that some of the patients are still on first line of the treatment, so this value will go up. And the true real world evidence that the patients who are not receiving immunotherapy in first line will not receive it in further lines in more than 9%. If you believe in immuno-oncology in gastric cancer, probably, you need to start early with the drug which is available for you and for your patients, given the registration, reimbursement, and patient's preference and biomarker. This was the final statement of what we shown today.

To conclude this study, in my opinion, the presentations which we gave today confirmed the previous data that pembrolizumab can be active agent for first-line treatment in metastatic or locally advanced gastric cancer not amenable for the resection. And, in these HER2-negative populations, the positive outcomes were seen regardless their PD-L1 status. Although there was increased magnitude of benefit in the patients with higher PD-L1 expression, it's important to notice that PD-L1 >1 is quite strong prognostic and predictive factor for this population and for these patients.

Thank you again for listening, and thank you if you are attending here the congress.

Source:

Wyrwicz L, Oh D, Weber P, et al. Additional data from the KEYNOTE-859 study of pembrolizumab plus chemotherapy versus placebo plus chemotherapy for advanced HER2-negative gastric or gastroesophageal junction (G/GEJ) cancer. Presented at World Congress on Gastrointestinal Cancers; June 28-July 1, 2023; Barcelona, Spain. Abstract O-3