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1w

Did you know? Immune checkpoint inhibitors targeting the PD-1/PD-L1 axis have produced durable, long-term survival in a subset of patients across multiple solid tumor types. A pooled analysis of 5-year overall survival data from landmark trials in melanoma, NSCLC, and renal cell carcinoma found that patients achieving a response to checkpoint inhibition had estimated 5-year survival rates of 34–48% — compared to under 5% historically in these metastatic settings. Predictive biomarkers including PD-L1 expression, tumor mutational burden, and microsatellite instability status continue to refine patient selection.

In your practice, how are you integrating multiple predictive biomarkers — PD-L1 CPS, TMB, and MSI status — to guide immunotherapy selection and sequencing, particularly in tumor types with overlapping biomarker indications?

NCCN Guidelines

In your practice, how are you integrating multiple predictive biomarkers — PD-L1 CPS, TMB, and MSI status — to guide immunotherapy selection and sequencing, particularly in tumor types with overlapping biomarker indications?

  • 1w
    Usually depends on the given indication, for instance PDL1 is important in mTNBC but then for CRC we really more on MSI. I hardly consider TMB aside from trying to consider agnostic use of pembrolizumab when no other indications met or left.
  • 2w
    I use these biomarkers complementarily rather than hierarchically. PD-L1 CPS remains the most tumor-specific guide when the indication is CPS-driven, while MSI-H/dMMR is a strong tumor-agnostic marker that can support immunotherapy regardless of PD-L1; TMB-high is an additional consideration, particularly when PD-L1 is negative or equivocal.
  • 2w
    This is a very difficult task because they are naturally all pieces of the pie. Like with clinical factors, no one single factor is complete without everything else.
  • 4w
    MSI-H/dMMR: usually the strongest reason to consider immunotherapy when applicable. PD-L1 CPS: helpful for selecting or prioritizing immunotherapy in cancers where CPS is validated. TMB: generally a supportive factor rather than a stand-alone decision-maker. When biomarkers overlap, I consider tumor type, prior therapy, clinical trial data, comorbidities, and toxicity risk rather than simply counting positive biomarkers.
    For sequencing, I favor evidence-based first-line regimens and reserve later-line immunotherapy for settings with demonstrated benefit.
  • 4w
    Renal cell and NSCLC both have immune therapy indications regardless of PD-L1 CPS, TMB or MSI status. However, in lung disease the IO must be used with chemo unless PD-L1 is > 50%. So, in frail patients with poor PS, IO markers to see if single agent IO is an option in metastatic NSCLC without another targetable genomic marker. Renal cell carcinoma has a good overall response to IO. IF a patient does or does not have a marker showing improved response to IO, it is more a prognostic vs a therapeutic target at this time.

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