Overview
- An ESMO Open pooled ad hoc analysis of 1,072 patients from SPOTLIGHT and GLOW found higher estimated efficacy for zolbetuximab plus chemotherapy when patients who discontinued early or had inadequate exposure due to nausea/vomiting were censored.
- With censoring, median PFS was 10.4 vs 8.2 months (HR 0.65) and median OS was 17.9 vs 13.7 months (HR 0.69) for zolbetuximab vs placebo, compared with 9.2 vs 8.2 months and 16.4 vs 13.7 months before censoring.
- Nausea (46.5%) and vomiting (41.0%) peaked on day 1 of the first infusion, fell by day 2 (23.2% and 24.4%), and declined further with subsequent doses.
- Use of a three‑drug antiemetic regimen at cycle 1 day 1 was associated with higher rates of no nausea (60.8%) and no vomiting (75.3%), and steroid premedication correlated with more patients reporting no nausea (57.9% vs 49.7%).
- Nausea/vomiting led to early discontinuation or inadequate exposure in 9.9% on zolbetuximab vs 0.6% on placebo, with higher rates in White than Asian patients; the regimen received FDA first‑line approval in 2024 for HER2‑negative, CLDN18.2‑positive gastric/GEJ adenocarcinoma.