Markus Eckstein: A huge paper corroborating results that we published in European Urology for urothelial cancer

Markus Eckstein, Senior Physician/Pathologist and Clinician Scientist at the University Hospital Erlangen, shared a post on X by Annals of Oncology, adding:

“This is a huge paper corroborating results that we published in European Urology for urothelial cancer! (link)

• in longitudinal samples latest/proximal PD-L1 status before ICI is predictive but not PD-L1 status in older samples.
• Same applies for TMB!

Why is this important?

• Tissue sampling time point and location matters, but tissue collection strategy in clinical trials is often shady!
• Proper tissue strategies, I.e. including latest tissue ideally from distant metastasis leads to reliability of biomarkers!
• Thus, we need more sophisticated and transparent tissue and biomarker strategies in clinical trials.”

Quoting Annals of Oncology’s post about the recent paper:

“Among 402 PD-L1 and 413 TMB sample pairs, PD-L1 concordance was moderate, but TMB concordance was high. About 20% of cases had large PD-L1 variations, and a TPS change of 50% or more(≥+50% in 9.7% and ≤-50% in 8.0%). Time between biopsies affected PD-L1 but not TMB concordance.

Acquired copy no. loss of CD274 (PD-L1), PDCD1LG2 (PD-L2), and JAK2, and intervening ICI were associated with PD-L1 low. In patients with multiple PD-L1 assessments pre ICI, patients with PD-L1 ≥1% in all samples, compared to patients with at least one PD-L1 <1% and another PD-L1 ≥1%, had high ORR and PFS.

In patients with multiple TMB assessments pre ICI, patients with TMB ≥10 mut/Mb at most recent assessment, compared to patients with TMB <10 mut/Mb, had longer PFS and OS; no differences were observed when patients were categorized using the oldest TMB assessment to ICI therapy.”