In a thought-provoking conversation, Prof Jeroen Dekervel, a GI Oncologist at UZ Leuven, had the privilege of speaking with Dr. Kohei Shitara, a globally recognized expert in gastric cancer. Their dialogue centered around the Keynote 585 trial, a significant development in the treatment of advanced gastric and gastroesophageal junction cancers. The discussion is summarized below.
Current Treatment Paradigm:
The management of gastric cancer exhibits noteworthy variations between Western and Eastern regions. Across the globe, surgery has remained the cornerstone of treatment. However, the persistence of a high recurrence rate post-surgery has long been a pressing concern. A key point of interest in the medical community is the integration of immunotherapy into the perioperative setting, offering a promising avenue for improving outcomes.
Trial Design:
The Keynote 585 trial was designed with a dual cohort approach. The first cohort aimed to assess the combination of pembrolizumab, an immune checkpoint inhibitor, with chemotherapy in the perioperative setting. Meanwhile, the second cohort was designed to investigate the feasibility and potential benefits of the FLOT regimen in combination with pembrolizumab.
Trial Endpoints:
The Keynote 585 trial focuses on multiple primary endpoints, including pathological complete response, partial response, event-free survival (EFS), and overall survival (OS). The study revealed a significant difference in pathological complete response, underscoring the potential of the pembrolizumab-chemotherapy combination. However, the trial suggests that while the results may show a promising trend in favour of pembrolizumab concerning EFS, they do not confirm statistical significance for EFS at this stage. The OS data, a crucial endpoint in oncology, are still in the process of maturation, leaving room for further insights in the future.
Safety and Surgical Outcomes:
An essential aspect of the trial was to ensure that curative surgery remained unaffected in both treatment groups. The results indicated that patients in the study could proceed to surgery in a timely manner without compromising surgical outcomes. Notably, anticipated immune-mediated adverse events were managed effectively. This is a significant step in demonstrating the viability of pembrolizumab in the perioperative setting.
Moving Forward:
As the trial progresses, key questions arise regarding the future of gastric cancer treatment. The results suggest that patient selection based on biomarkers may be a pivotal factor in further improving outcomes. Ongoing global studies, including the Matterhorn study, which incorporates FLOT chemotherapy as a backbone, may provide additional insights and offer a more relevant approach to treatment.
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