ASCO GI 2023 | PARADIGM: panitumumab versus bevacizumab in RAS-wt mCRC
Kohei Shitara, MD, National Cancer Center Hospital East, Chiba, Japan, presents findings from the Phase III PARADIGM trial (NCT02394795) of panitumumab versus bevacizumab in patients with RAS wild-type, left-sided metastatic colorectal cancer (mCRC). Patients received modified-FOLFOX6 with panitumumab or bevacizumab, where overall survival was the primary endpoint. Negative hyperselection using ctDNA rather than tumor sidedness may identify patients who will benefit from panitumumab more efficiently. 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)
Okay, this SPOTLIGHT is a global randomized double-blinded controlled trial to compare FOLFOX plus zolbetuximab and FOLFOX placebo for patient with gastric GEJ adenocarcinoma first line with Claudin 18.2-positive and HER-2 negative expression. Claudin 18.2 is a tight junction protein which is normally expressed in gastric mucosal cells and become an attractive target for gastric cancers...
Okay, this SPOTLIGHT is a global randomized double-blinded controlled trial to compare FOLFOX plus zolbetuximab and FOLFOX placebo for patient with gastric GEJ adenocarcinoma first line with Claudin 18.2-positive and HER-2 negative expression. Claudin 18.2 is a tight junction protein which is normally expressed in gastric mucosal cells and become an attractive target for gastric cancers.
In this study, the primary endpoint was progression-free survival, and overall survival was also key secondary endpoint. So as a result, we screened more than 2,700 patients within four years. And about 78% patient had Claudin 18.2-positive tumors. And finally, we randomized 565 patients into this trial. So as a primary endpoint, PFS, this was significantly improved by the combination. Median overall survival was 10.6 months with zolbetuximab and FOLFOX, and 8.7 months with placebo plus FOLFOX. And hazard ratio was .75 with significant p value. So this trial showed a PFS improvement.
Also, overall survival as one of the key secondary endpoint was also significantly improved. Median overall survival was 18.2 months with zolbetuximab and 15.5 months with placebo. I think this 18-months median survival should be our longest median survival in first-line gastric cancer trial in front-line. And hazard ratio was .75, with again significant p value. So this trial met both PFS and overall survival endpoint.
And as a toxicity we observed a slightly higher nausea and vomiting as a notable toxicity of the zolbetuximab because Claudin is expressed in normal gastric mucosal cells so this hit their stomach and the patient have nausea and vomiting, but usually this happened after very early cycle of treatment At the first or second infusion and very well managed by infusion-dose adjustment and the incidence of nausea and vomiting was apparently decreased at subsequent cycle.
So in summary, this study show that significant improvement of PFS and overall survival with zolbetuximab plus FOLFOX for Claudin 18.2-positive tumor. And I believe this may be the new potential standard of care in the future.
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