Significantly improved survival
In the current phase 3 trial, dubbed SPOTLIGHT, Dr. Shitera and colleagues randomly assigned 565 patients to receive either zolbetuximab IV 800 mg/m2 (cycle 1, day 1) followed by 600 mg/m2 (cycle 1, day 22, and every 3 weeks in later cycles) plus mFOLFOX6 IV for four 42-day cycles or placebo plus mFOLFOX6.
All patients were treatment naive with CLDN18.2/HER2− locally advanced unresectable or metastatic mG/GEJ adenocarcinoma. Treatment continued until disease progression or discontinuation criteria were met.
The primary endpoint of progression-free survival was statistically significantly improved among patients who received combination therapy with zolbetuximab, compared with patients who received placebo (median 10.61 vs. 8.67 months; hazard ratio, 0.751; P = .0066).
“This was highly significant, and the study met its primary endpoint,” said Dr. Shitera. “The subgroup analysis shows that there was also consistent benefit in the prespecified subgroups.”
In similar fashion, overall survival was also significantly improved (median, 18.23 vs. 15.54 months; HR, 0.750; P = .0053).
However, the overall response rate was similar between groups (60.7% vs. 62.1%).
Toxicity was higher in the zolbetuximab group. The most common treatment-related adverse events were nausea (82.4% vs. 60.8% in zolbetuximab vs. placebo arms), vomiting (67.4% vs. 35.6%), and decreased appetite (47.0% vs. 33.5%), although the incidence of serious events was similar between the groups (44.8% vs. 43.5%).
Most events occurred at first or second cycle and could be resolved, Dr. Shitera noted, and treatment-related events were consistent with those of previous studies.
The study was funded by Astellas Pharma. Dr. Shitara has relationships with numerous pharmaceutical companies, as listed in the abstract.
The Gastrointestinal Cancers Symposium is sponsored by the American Gastroenterological Association, the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology.
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