The gold standard clinical endpoint–and what functional biomarkers ultimately predict.
Surrogate endpoints like progression-free survival (PFS) or response rate are useful for accelerating drug development, but OS is what ultimately matters to patients. A therapy that shrinks tumors but doesn't extend life has limited value.
Regulatory agencies increasingly require OS data for full approval. Biomarkers that predict OS–rather than just response–provide the most clinically actionable information.
The Ultimate Endpoint: Overall survival measures how long patients live. It's the most important cancer endpoint because it directly answers: does this treatment save lives?
Other Endpoints: Tumor shrinkage and progression-free survival are useful but can be misleading. Only OS definitively shows life extension.
The landmark PD-1/PD-L1Loading... iFRET studies demonstrated that checkpoint engagement correlates with OS in immunotherapy-treated patients. High PD-1/PD-L1 interaction (paradoxically) predicted better survival–because it indicates the tumor is using this pathway, making it vulnerable to blockade.
Similarly, Akt activationLoading... measured by FRET correlated with OS in breast cancer (2014) and ccRCC (2017), while expression-based markers showed no correlation. This pattern–function predicts survival, expression doesn't–is the core value proposition of functional biomarkers.
The Test: For a biomarker to be clinically meaningful, it should correlate with survival. Patients with "good" biomarker status should live longer.
QF-Pro Evidence: PD-1/PD-L1 engagement by iFRET correlated with overall survival (P=0.05) in melanoma. PD-L1 expression did not (P=0.87). This is the evidence that functional measurement matters.
