Post-treatment ctDNA positivity is a powerful predictor of high recurrence risk in gastric cancer patients. However, this advanced diagnostic knowledge creates a clinical dilemma, as there is no evidence-based consensus on how to act on the results, forcing clinicians to make treatment decisions without supporting data.
The Matterhorn study found that adding the immunotherapy drug Durvalumab to FLOT chemotherapy significantly improved survival in localized gastric cancer. Surprisingly, this benefit extended to patients with low or negative PD-L1 expression, challenging the biomarker's predictive value for immunotherapy efficacy in this perioperative setting.
Despite being the backbone for new combination therapies in trials like Matterhorn, the FLOT chemotherapy regimen has significant toxicity. Approximately 30% of patients discontinue treatment due to adverse events, and only half manage to complete the post-surgery adjuvant portion, posing a major clinical challenge in real-world settings.
New targeted therapies like Zanidatamab and Zolbetuximab show great promise but cause significant side effects like diarrhea and nausea. Their successful clinical adoption hinges on proactive management using detailed guidelines and prophylactic medications, as toxicity can be severe enough to force treatment discontinuation despite the drug's efficacy.
The Skyscraper 07 trial failed its primary endpoint for a TIGIT/PD-L1 inhibitor combo in esophageal cancer. However, a secondary analysis of the Atezolizumab-only arm revealed significant survival benefits. This unexpected positive signal from a technically "negative" study may lead to a new standard of care, pending regulatory interpretation.
The SANO trial's 'watch-and-wait' approach for esophageal cancer avoids initial surgical risks, showing superior survival for the first two years. However, the survival curves cross after that point, suggesting that surgery, despite its initial toll, may offer better long-term outcomes for patients who can tolerate the procedure.