Retrospective Analysis of Zolbetuximab-Associated Hypoalbuminemia in Claudin 18.2-Positive Advanced Gastric Cancer.

BACKGROUND

Hypoalbuminemia has been recognized as a characteristic adverse event associated with zolbetuximab plus chemotherapy in the treatment of claudin 18.2-positive advanced gastric cancer. However, its incidence, clinical predictors, and management in real-world settings remain unclear.

AIMS: We aimed to characterize the course of hypoalbuminemia during zolbetuximab-based therapy and identify factors associated with its severity and recovery.

METHODS AND

RESULTS

We retrospectively analyzed patients with advanced gastric cancer treated with zolbetuximab plus chemotherapy at a single center, tracking serial serum albumin levels. Severe hypoalbuminemia was defined as a nadir albumin < 2.0 g/dL and/or a ≥ 1.0 g/dL decrease from baseline. Associations between severe hypoalbuminemia and clinicopathological factors were assessed, along with its management strategies. A total of 39 patients were included in the analysis. Hypoalbuminemia occurred in all patients, and 20 (51.3%) developed severe hypoalbuminemia. Prior total gastrectomy was associated with a lower incidence of severe hypoalbuminemia (0% vs. 58.8%, p = 0.02), whereas persistent nausea and/or vomiting beyond the zolbetuximab infusion during the first cycle was associated with a higher risk (63.0% vs. 25.0%, p = 0.04). Recovery of serum albumin levels was observed in 18 patients (46.2%) and occurred more frequently among those who temporarily interrupted zolbetuximab plus chemotherapy or zolbetuximab alone (66.7% vs. 28.6%, p = 0.03).

CONCLUSION

Severe hypoalbuminemia was common in patients receiving zolbetuximab plus chemotherapy in real-world practice. The absence of prior total gastrectomy and the presence of persistent post-infusion nausea and/or vomiting may help identify patients at risk. The observed association between temporary treatment interruption and albumin recovery may provide insights into the management of hypoalbuminemia.