Florian Lordick, Oncologist, Professor of Medicine at the University of Leipzig, Head of Medical Oncology, Director of the Comprehensive Cancer Center Central Germany, shared on LinkedIn:
“How should we choose first-line treatment when CLDN18.2 and PD-L1 coexist in advanced gastric cancer?
I am pleased to share our new publication in ESMO Open, led by Kohei Shitara and Sun Young Rha, addressing this increasingly relevant clinical question.
In this Bayesian network meta-analysis, we compared zolbetuximab plus chemotherapy with immune checkpoint inhibitor–based regimens across different PD-L1 CPS levels in HER2-negative advanced gastric and gastroesophageal junction adenocarcinoma.
An interesting picture emerges:
- At PD-L1 CPS 1–<10, zolbetuximab showed efficacy that was similar or numerically favorable compared with ICI-based approaches.
- At CPS ≥10, the balance shifted toward immune checkpoint inhibition in the primary analysis.
- Importantly, CLDN18.2 and PD-L1 represent biologically distinct—and potentially complementary—therapeutic pathways.
Of course, these are indirect comparisons, not head-to-head evidence, and the methodological limitations of a network meta-analysis need to be kept firmly in mind.
Nevertheless, I believe the study adds an important piece to the evolving concept of biomarker-informed treatment selection in gastric cancer. Rather than asking which biomarker ‘wins’, the future may increasingly be about understanding how CLDN18.2, PD-L1, HER2 and MSI jointly define the optimal therapeutic strategy.
And perhaps the next step is already obvious: how can we best combine these approaches?
Many thanks to Kohei Shitara, Sun Young Rha, Samuel Klempner, and all co-authors for this excellent collaboration.”
Title: Zolbetuximab plus chemotherapy versus immune checkpoint inhibitor regimens by programmed death-ligand 1 combined positive score in locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma: a Bayesian network meta-analysis
Authors: K. Shitara, S.Y. Rha, S.J. Klempner, F. Lordick, R. Ranganath, M. Oh, R.H. Getzenberg, G. Gourgioti, X. Chai, H. Yang
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