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Gastrointestinal cancer

Zolbetuximab moves into the SPOTLIGHT

Nature Reviews Clinical Oncology volume 20, page 354 (2023)Cite this article

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Patients with HER2– advanced-stage gastric or gastro-oesophageal junction (G/GEJ) cancers typically receive 5-fluorouracil, folinic acid and oxaliplatin (mFOLFOX6) or capecitabine and oxaliplatin (CAPOX), although survival with these regimens tends to be poor. Evidence suggests that CLDN18.2, a gastric-specific isoform of the tight-junction protein claudin 18 that is overexpressed in the majority of G/GEJ cancers, is a promising therapeutic target. Now, data from the phase III SPOTLIGHT trial show that addition of the anti-CLDN18.2 antibody zolbetuximab to mFOLFOX6 improves outcomes in this setting.

A total of 565 patients with CLDN18.2+ advanced-stage G/GEJ adenocarcinomas were randomly assigned (1:1) to receive first-line mFOLFOX6 plus either zolbetuximab or placebo. Progression-free survival (PFS) was the primary end point. At a median follow-up duration of at least 12.7 months, the PFS duration was longer in patients receiving zolbetuximab (median 10.6 months versus 8.7 months with placebo; HR 0.75, 95% CI 0.60–0.94; P = 0.007). Zolbetuximab also prolonged the overall survival duration (median 18.2 months versus 15.5 months; HR 0.75, 95% CI 0.60–0.94; P = 0.005).

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References

Original article

  • Shitara, K. et al. Zolbetuximab plus mFOLFOX6 in patients with CLDN18.2-positive, HER2-negative, untreated, locally advanced unresectable or metastatic gastric or gastro-oesophageal junction adenocarcinoma (SPOTLIGHT): a multicentre, randomised, double-blind, phase 3 trial. Lancet https://doi.org/10.1016/S0140-6736(23)00620-7 (2023)

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  1. Nature Reviews Clinical Oncology http://www.nature.com/nrclinonc

    Diana Romero

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  1. Diana Romero
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Correspondence to Diana Romero.

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Romero, D. Zolbetuximab moves into the SPOTLIGHT. Nat Rev Clin Oncol 20, 354 (2023). https://doi.org/10.1038/s41571-023-00773-y

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