ASCO GI 2023 | SPOTLIGHT: zolbetuximab and m-FOLFOX6 in CLDN18.2+, HER2- GEJ cancer
Kohei Shitara, MD, National Cancer Center Hospital East, Chiba, Japan, provides an overview of findings from the Phase III SPOTLIGHT trial (NCT03504397), which assessed zolbetuximab in patients with CLDN18.2-positive, HER2-negative, locally advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma. Zolbetuximab is a first-in-class monoclonal antibody targeting CLDN18.2, and patients were given modified-FOLFOX6 with or without zolbetuximab. 2735 patients were recruited, and addition of zolbetuximab significantly improved progression-free survival and overall survival. This interview took place at the American Society of Clinical Oncology (ASCO) 2023 Gastrointestinal Cancers (GI) Symposium in San Francisco, CA.
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Transcript (edited for clarity)
Yeah, PARADIGM is a Japanese very important Phase III trial to compare FOLFOX plus anti-EGFR panitumumab versus FOLFOX plus anti-VEGF inhibitor bevacizumab in patient with first-line RAS wild-type and especially left-sided primary colorectal cancer.
This study result was already presented at previous ASCO meeting. It showed significant improvement of overall survival in this population with FOLFOX plus panitumumab...
Yeah, PARADIGM is a Japanese very important Phase III trial to compare FOLFOX plus anti-EGFR panitumumab versus FOLFOX plus anti-VEGF inhibitor bevacizumab in patient with first-line RAS wild-type and especially left-sided primary colorectal cancer.
This study result was already presented at previous ASCO meeting. It showed significant improvement of overall survival in this population with FOLFOX plus panitumumab. Survival in right-sided population showed no large difference.
In this presentation, we first reported biomolecular analysis using ctDNA. We tested the ctDNA baseline biomarker to analyze some gene alteration which related to the primary resistant to anti-EGFR therapy. This the ctDNA result were available for more than 90% of patients. As a result, 28% of patient had at least one gene alteration, including KRAS, BRAF, EGFR-ECD, MET or HER2 amplification, and PTEN mutation, as well as three types of fusion. In other words, 72% of patients had no this kind of special gene alteration. The patient with gene alteration was revealed to be higher in the right side than left side, as expected.
Moving to treatment outcome, overall survival was clearly or apparently improved with FOLFOX plus panitumumab, especially in patients without this kind of gene alteration, so unresected population. In the left side of population with unresection, median overall survival was improved by seven months. In contact, even in left side of the population, if patient had a gene alteration, no survival benefit was observed. Very importantly, even in the right side population, if patient have no special gene alteration, overall survival is suggested to be improved by panitumumab combination. Again, overall survival was inferior in the right side population with gene alteration.
(02:17)
So while this exploratory preplanned biomarker analysis from this PARADIGM Phase III trial suggested a negative hyperselection by multiple gene alteration, rather than tumor sidedness, may identify the appropriate patient for their first-line FOLFOX plus panitumumab for colorectal cancer.
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