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Gastrointestinal Tumor Research and Treatment / Gastric Cancer Management and Outcomes · Journal article
Discover Oncology · September 7, 2026
A consensus or society position rather than new primary data.
This expert review distinguishes evidence-supported clinical practice from exploratory biomarker strategies in gastric cancer. CLDN18.2-directed therapy (zolbetuximab plus chemotherapy) is supported by Phase III randomized evidence (SPOTLIGHT and GLOW) when using treatment-specific assays and validated thresholds; FGFR2b-directed therapy remains investigational despite Phase III data because of attenuation of overall-survival effect at longer follow-up. Current clinical implementation should remain anchored to validated companion diagnostics and prospective trial evidence, while complementary biomarkers and re-testing strategies are presented as research hypotheses requiring prospective validation.
Narrative review. Patients with gastric and gastroesophageal junction adenocarcinoma; synthesis of prospective randomized trials and translational evidence organized into three levels: evidence supporting current practice, emerging clinical/translational evidence, and author-proposed hypotheses. Intervention: CLDN18.2-directed therapy (zolbetuximab plus chemotherapy) and FGFR2b-directed therapy; companion diagnostic strategies including IHC, genomic profiling, transcriptomics, multiplex immunofluorescence, digital pathology, and AI-assisted pat….
SPOTLIGHT and GLOW provide randomized phase III evidence for zolbetuximab plus chemotherapy in CLDN18.2-selected patients with treatment-specific assay and threshold FAST and FIGHT provide supportive phase II evidence for CLDN18.2-directed therapy FORTITUDE-101 supplies phase III evidence for FGFR2b enrichment but with attenuation of overall-survival effect at longer follow-up
Safety was not reported in the material analysed. Check the source before drawing any conclusion about harm.
Clinicians should continue using treatment-specific CLDN18.2 companion diagnostics and validated thresholds for zolbetuximab selection, as supported by Phase III trials. FGFR2b-directed therapy should not yet be adopted outside clinical trials, as overall-survival benefit attenuates at longer follow-up. Emerging biomarker strategies require prospective validation before clinical implementation.
A narrative review synthesizing evidence across randomized trials and translational studies to distinguish established clinical practice from exploratory strategies in gastric cancer biomarker-directed therapy.
As stated by the source record.
Clinicians should continue using treatment-specific CLDN18.2 companion diagnostics and validated thresholds for zolbetuximab selection, as supported by Phase III trials. FGFR2b-directed therapy should not yet be adopted outside clinical trials, as overall-survival benefit attenuates at longer follow-up. Emerging biomarker strategies require prospective validation before clinical implementation.
Graded across the dimensions that decide whether you should act, each from what the source actually supports. There is no single score, and where a dimension was not assessed it says so.
What is missing. This record has no reported figures. That is a gap in the analysis, not a judgement about the study.
CLDN18.2-directed therapy has expanded biomarker-selected treatment options for gastric and gastroesophageal junction adenocarcinoma, whereas FGFR2b-directed therapy has shown clinical activity but remains investigational. Clinical interpretation depends on treatment-specific assays, thresholds, sampling quality, and the strength of evidence supporting each intervention. This review distinguishes evidence-supported clinical practice from exploratory biomarker strategies and author-proposed conceptual frameworks. We synthesized clinical and translational evidence across immunotherapy-era standards of care, emphasizing trial design, diagnostic variability, intratumoral heterogeneity, treatment deliverability, and implementation barriers. Evidence was organized into three levels: prospective evidence supporting current practice, emerging clinical or translational evidence, and author-proposed hypotheses requiring prospective validation. SPOTLIGHT and GLOW provide randomized phase III evidence for zolbetuximab plus chemotherapy in patients selected with a treatment-specific CLDN18.2 assay and threshold. FAST and FIGHT provide supportive phase II evidence, while FORTITUDE-101 supplies phase III evidence for FGFR2b enrichment but with attenuation of the overall-survival effect at longer follow-up; FGFR2b-directed therapy therefore remains investigational. Genomic profiling, transcriptomics, multiplex immunofluorescence, digital pathology, and artificial intelligence-assisted pathology may complement IHC, but none currently replaces a validated protein-based companion diagnostic. Re-testing, dependency-first selection, cutoff engineering beyond validated criteria, and the deliverability gate remain hypothesis-generating or selectively applicable strategies rather than established standards. Current clinical implementation should remain anchored to treatment-specific companion diagnostics, regulatory criteria, and prospective trial evidence. Complementary biomarkers and adaptive re-testing strategies are promising but require prospective validation. The dependency-first, cutoff-engineering, and deliverability frameworks are presented as research hypotheses and not as clinical recommendations.
Taken from the source record, never inferred. Follow any of these and new work involving them reaches your briefing.