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Given that PD-L1 scores for gastroesophageal cancers can be exceptionally variable between labs, some clinicians prefer a simple CPS cutoff of 1. This 'some expression versus no expression' approach is considered more reproducible and practical for decision-making than relying on specific higher scores that may not be consistent across different testing sites.
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Contrary to its role in lung cancer, PD-L1 expression does not predict benefit from immunotherapy in mesothelioma. Data from major trials shows similar outcomes regardless of PD-L1 status, leading clinicians to omit this test entirely and streamline treatment decisions.
Beyond clinical validation, the adoption of novel biomarkers like microRNA is hindered by practical lab issues. Disagreements over sample type (serum vs. plasma), establishing universal cutoffs, and achieving high concordance between different testing centers are critical, non-clinical hurdles that must be overcome for widespread clinical use.
In the increasingly common scenario of gastric cancer with multiple biomarkers (HER2, PD-L1, Claudin), experts recommend a clear hierarchy. Based on data maturity, HER2-targeted therapy is the first choice, followed by PD-L1 immunotherapy, with Claudin-targeted therapy third.
A PD-L1 CPS score of zero should not automatically disqualify patients with metastatic anal cancer from receiving immunotherapy. The clinical distinction between a CPS of zero and one is marginal, and given the therapy's potential for benefit and low toxicity, clinicians should give patients the benefit of the doubt and offer the treatment.
Despite major advances in immunotherapy, patient selection remains crude compared to targeted therapies. PD-L1 is still the primary, yet imperfect, biomarker used. Dr. Carbone highlights an urgent need to develop better predictive biomarkers to customize immunotherapy regimens, as is standard for targeted agents.
An expert argues forcefully that the PD-L1 biomarker should be "ditched" in bladder cancer. Citing its repeated failure to predict overall survival benefit across multiple major trials, it is deemed an oversimplified and unreliable tool that leads to both over- and under-treatment of patients.
Unlike breast or lung cancer where a biomarker's effectiveness persists across treatment stages, biomarkers in upper GI cancers often fail to show similar efficacy when moved from one line of therapy to another. This suggests a more variable and rapidly changing tumor biology.
Despite stratifying patients by PD-L1 status, the AGO-OV-229 trial found it was not a predictive marker. Hazard ratios for survival were similar for both PD-L1 positive and negative tumors, challenging its utility for patient selection.
In the increasingly common scenario of a patient with multiple positive biomarkers, a clear hierarchy exists for treatment decisions. Based on the robustness and maturity of clinical trial data, HER2-directed therapy is the top priority, followed by PD-L1 immunotherapy, with Claudin-18.2 targeting considered third.
The successful KEYNOTE-564 trial intentionally used a pragmatic patient selection model based on universally available pathology data like TNM stage and grade. This approach avoids complex, inconsistently applied nomograms, ensuring broader real-world applicability and potentially smoother trial execution compared to studies relying on more niche scoring systems.