Markus Eckstein (@Markuseckstein3)
@Markuseckstein3
#Pathologist# #Physician# Scientist @UniFAU University Hospital Erlangen, Germany #pathology# #biomarker_research# - My opinions are my own
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Do we understand PDAC? These tumors have a particular desmoplastic stroma, are hypovascularized, and exhibit proven high osmotic pressure in their stroma. As indicated by the 0% ORR achieved by T-DXd in 2/3+ PDACs and the lack of additive value from zolbetuximab (also an antibody), this cannot be explained solely by chemoresistance. Anti-PD-1 antibodies were also inactive.
There is no strong evidence for this, but antibodies probably cannot reach PDAC tumor cells. This is underscored by the 0% ORR to T-DXd, while some patients respond to small-molecule chemotherapy.
How can we overcome this? Potentially with next-generation small peptide compounds or direct tumor stroma remodeling.
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Zolbetuximab plus gemcitabine and nab-paclitaxel in CLDN18.2+ metastatic PDAC: phase II GLEAM study
@ESMO-GI
👉Primary endpoint not met, no OS & PFS benefit
👉Toxicity manageable
🧐Not the right drug, but maybe the right target
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