ASCO GI Highlights

The SPOTLIGHT study: Promising Effect of Zolbetuximab plus mFOLFOX6

The SPOTLIGHT study has achieved its primary endpoint, potentially paving the way for a new first-line treatment option for individuals with Claudin 18.2 (CLDN18.2)-positive, HER2-negative, locally advanced unresectable or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma.

Results from the SPOTLIGHT study, one of the longest phase III trials for patients with CLDN18.2+ / HER2- locally advanced unresectable or metastatic gastric or gastroesophageal junction (mG/GEJ) adenocarcinoma, were presented during the 2023 ASCO Gastrointestinal Cancers Symposium.

The SPOTLIGHT trial enrolled 550 patients with CLDN18.2+ / HER2- locally advanced unresectable or mG/GEJ adenocarcinoma in a phase III randomized study. Patients were randomly assigned to receive either zolbetuximab plus leucovorin, fluorouracil, and oxaliplatin (mFOLFOX6) or placebo plus mFOLFOX6 as their first-line treatment in a 1:1 ratio. Both groups had similar baseline characteristics. The study involved participants with a median age of 62 years, consisting of 62% men, 69% non-Asian, and 31% Asian. The majority (77%) of the participants had primary cancer instomach, and 22.6% had metastatic cancer in three or more organs.

Clinically significant improvement of PFS and OS

Kohei Shitara, MD of the National Cancer Center Hospital East, Kashiwa, Japan, stated that the median progression-free survival (PFS) was 10.6 months in the combination arm and 8.67 months in the placebo arm with a hazard ratio of 1.75 and P value of 0.0066, meeting the primary endpoint. The study also showed a PFS benefit in most subgroups. The study's positive results in terms of PFS were also reflected in the median overall survival (OS), even though OS was not the primary endpoint. The combination arm had a median OS of 18.2 months, which was significantly longer than the 15.54 months seen in the placebo arm, with a hazard ratio of 0.75 and a significant P value.

Clinical implications

Dr. Wungki Park, a medical oncologist and translational research scientist at the Memorial Sloan Kettering Cancer Center in New York suggests that the findings from the SPOTLIGHT study may lead to the development of a new treatment plan. Hence, zolbetuximab in combination with mFOLFOX6 could potentially be established as the new standard of care for patients with locally advanced (LA) unresectable or metastatic gastric or gastroesophageal junction (mG/GEJ) adenocarcinoma who have the biomarker CLDN18.2+ / HER2-.

Conclusion

The SPOTLIGHT study is a phase III trial with one of the superior OS rates for patients with CLDN18.2+ / HER2- locally advanced unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma. The study has demonstrated that the combination of zolbetuximab and modified FOLFOX 6 significantly improved both PFS and OS while maintaining a tolerable safety profile. Although both groups had similar rates of adverse events, the active arm experienced more frequent nausea and vomiting.

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