In the treatment of cancer , combination therapies are gaining more and more importance , those that seek to take advantage of the synergies between different treatments to overcome the defense mechanisms of tumor cells and thus be able to defeat the disease. Along these lines are the data from an interim analysis of the phase III KEYNOTE-811 trial, which has just been published in the journal Nature .
The results of this international study, with the participation of the Vall d’Hebron Institute of Oncology ( VHIO ), demonstrate for the first time that adding pembrolizumab – an antibody directed against a type of receptor (known as PD-1) on the cell surface – The existing therapy improves the results in patients with advanced gastric cancer with overexpression of HER2 , and increases their objective response rate – that is, the tumor has reduced its size or disappeared after treatment.
According to the study, adding pembrolizumab to existing therapy improves outcomes in advanced gastric cancer patients with HER2 overexpression
Approximately 15-20% of advanced gastric or gastroesophageal junctional adenocarcinomas – malignant tumors originating in a gland – present overexpression of the HER2 gene. For this reason, for more than a decade the conventional treatment for this population consisted of the combined administration of chemotherapy with trastuzumab – an antibody directed against HER2.
“With the data obtained in this new trial, it has been observed that adding a new drug, in this case pembrolizumab, improves the response rate to treatment in this population of HER2-positive gastric cancer patients. It is the first time that an anti-PD-1 therapy has shown, in this type of patient, an improvement in terms of objective response ”, explains Josep Tabernero , co-author of the study and director of the Vall d’Hebron Institute of Oncology (VHIO).
Promising data awaiting study conclusion
The KEYNOTE-811 trial was designed to further study the combination of pembrolizumab , trastuzumab, and chemotherapy in patients with HER2-positive advanced esophageal, gastroesophageal, or gastric adenocarcinoma, which in previous studies had demonstrated both clinical efficacy and manageable safety. For this, a total of 434 participants were recruited. The data of the first 264 patients included are already available, on whom the intermediate analysis was carried out, which has just been published in Nature and which had already been advanced at the congress of the European Society of Medical Oncology ( ESMO ) held this anus.
“These initial findings from KEYNOTE-811 suggest that this triple combination may be a transformative treatment option for HER2-positive gastric or gastroesophageal junction adenocarcinoma. Thus, they have served so that the United States Food and Drug Administration ( FDA ) has quickly approved its use. This is an unprecedented decision , since a decision has never been made based on intermediate results that are not evaluating the main variables of the study ” , explains the expert.
74.4% of the patients who received the triple combination (pembrolizumab, trastuzumab and chemotherapy) showed an objective response, that is, the tumor reduced its size or disappeared after treatment
According to this interim analysis, 74.4% of the patients who received the triple combination showed an objective response, while in the control group, who received the conventional chemotherapy treatment and trastuzumab plus a placebo, this was only 51.9%.
It was also observed that in the group receiving pembrolizumab the tumor size was markedly reduced and complete responses were induced in some participants.
“Although these are promising results, we must now wait to complete the study to see if this ultimately translates into both greater progression-free survival and better overall survival , which were the two main variables we wanted to study,” he adds. the director of the VHIO, who emphasizes the need to take these results with caution. Even so, he considers that this represents a further step in the fight against advanced disease in gastric cancer and reinforces the importance of associating therapeutic strategies that stimulate the immune response to conventional treatments.
Reference:
Janjigian et al . (2021) “Combined PD-1 and HER2 blockade for HER2-positive gastric cancer”. Nature. https://doi.org/10.1038/s41586-021-04161-3