Hacı Mehmet Türk

There is an urgent need for first-line treatment options for patients with human epidermal growth factor receptor 2 (HER2)-negative, locally advanced unresectable or metastatic gastric or gastroesophageal junction (mG/GEJ) adenocarcinoma. Claudin-18 isoform 2 (CLDN18.2) is expressed in normal gastric cells and maintained in malignant G/GEJ adenocarcinoma cells. GLOW (closed enrollment), a global, double-blind, phase 3 study, examined zolbetuximab, a monoclonal antibody that targets CLDN18.2, plus capecitabine and oxaliplatin (CAPOX) as first-line treatment for CLDN18.2-positive, HER2-negative, locally advanced unresectable or mG/GEJ adenocarcinoma. Patients (n = 507) were randomized 1:1 (block sizes of two) to zolbetuximab plus CAPOX or placebo plus CAPOX. GLOW met the primary endpoint of progression-free survival (median, 8.21 months versus 6.80 months with zolbetuximab versus placebo; hazard ratio (HR) = 0.687; 95% confidence interval (CI), 0.544-0.866; P = 0.0007) and key secondary endpoint of overall survival (median, 14.39 months versus 12.16 months; HR = 0.771; 95% CI, 0.615-0.965; P = 0.0118). Grade ≥3 treatment-emergent adverse events were similar with zolbetuximab (72.8%) and placebo (69.9%). Zolbetuximab plus CAPOX represents a potential new first-line therapy for patients with CLDN18.2-positive, HER2-negative, locally advanced unresectable or mG/GEJ adenocarcinoma. ClinicalTrials.gov identifier: NCT03653507 .

The clinical utility of tumor markers is limited due to their low specificity. CA 125, an ovarian tumor marker, is a sensitive but nonspecific tumor marker used especially in the follow-up of ovarian cancer for monitoring the efficacy of therapy and for early detection of recurrence. The use of the CA 125 serum assay as a single diagnostic tool is restricted by the fact that the antigen to CA 125 is also produced by normal epithelia (peritoneum, pleura, and pericardium). Since an elevated serum CA 125 level is a marker of ovarian cancer, a laparotomy is the final tool of the physician to clarify the etiology. However, unnecessary operations have been reported in the literature revealing no ovarian pathology (e.g. cirrhosis, tuberculous peritonitis or pancreatic cancer) in such patients. Elevated serum CA 125 levels require a cautious operative planning in patients without a notable tumor mass. A secondary interpretation is needed in case of elevated CA 125 levels whenever serosal (peritoneal, pleural, or pericardial) fluid is present.