Discussion
HER2-negative, nausea and vomiting, tumors
EVENTS, DISEASE, TUMORS, ADENOCARCINOMA
In GLOW, the addition of first-line zolbetuximab to CAPOX significantly improved PFS and OS in patients with CLDN18.2-positive, HER2-negative, locally advanced unresectable or mG/GEJ adenocarcinoma. GLOW confirmed the increased survival benefit of adding zolbetuximab to chemotherapy observed in previous phase 2 and 3 studiesAlthough the control arm in SPOTLIGHT performed better than expected, in GLOW, the control arm performed as expected, which is in line with other studies that suggest that CLDN18.2 is not a prognostic biomarkerGLOW demonstrated that CLDN18.2 is a prevalent biomarker in HER2-negative, locally advanced unresectable or mG/GEJ adenocarcinoma. In GLOW, 38.4% of screened patients with tumors assessable for CLDN18.2 expression had tumors that met the cutoff for CLDN18.2 positivity. In SPOTLIGHT, 38.4% of screened patients with tumors assessable for CLDN18.2 expression also had CLDN18.2-positive tumorsIn GLOW, the most common TEAEs observed in patients who received zolbetuximab plus CAPOX were nausea and vomiting; these events occurred at a more than 10% difference compared with patients who received placebo plus CAPOX. These results are consistent with the safety profile of zolbetuximab monotherapy and zolbetuximab plus chemotherapy observed in previous phase 1, 2 and 3 studiesThis study had some limitations. First, this study was underpowered to statistically determine the effectiveness of zolbetuximab plus CAPOX in the pre-specified subgroups. In all cases, these subgroups were relatively small, and so interpretations should be made with caution. Next, this study did not evaluate the combination of zolbetuximab with nivolumab. Chemotherapy was selected as a relevant comparator arm in GLOW because nivolumab was not approved in this patient population at the time of study initiation. Furthermore, there is a substantial number of patients in this population whose disease does not respond to nivolumab. The ILUSTRO study (Overall, treatment with zolbetuximab plus CAPOX led to statistically significantly prolonged PFS and OS compared to placebo plus CAPOX in patients with CLDN18.2-positive, HER2-negative, locally advanced unresectable or mG/GEJ adenocarcinoma. These results further confirm the survival benefits observed in the phase 3 SPOTLIGHT study