Daniel H. Ahn, DO, oncologist and internist, Mayo Clinic. In this video, he discusses the ASCO GI 2022 Abstract – REVERCEII (ACCRU-GI-1809): A randomized phase II study of regorafenib followed by anti-EGFR monoclonal antibody therapy versus the reverse sequencing for metastatic colorectal cancer patients previously treated with fluoropyrimidine, oxaliplatin and irinotecan.
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Origins:
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Regorafenib (R) is an oral multikinase inhibitor that inhibits several protein kinases involved in angiogenesis and oncogenesis, and it has been shown to improve survival in refractory metastatic colorectal cancer patients (mCRC). In patients (pts) with RAS wildtype (WT) mCRC, the current standard (std) treatment is sequential treatment with an anti-EGFR antibody (AEA) followed by R. R, which is given orally once day, may be more convenient and so preferred by patients than AEA. Regorafenib given before AEA resulted in a substantial 5.8 month (mo.) survival improvement in REVERCE, a Japanese trial, compared to the standard sequence. Based on these findings, a phase II trial in the United States is being planned to confirm the observed survival benefit from regorafenib sequencing prior to anti-EGFR monoclonal antibody therapy in REVERCE.
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Methodologies:
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REVERCEII is a randomized phase II study led by the Academic and Community Cancer Research United (ACCRU) network that compares R (dose escalation from 80mg to 160mg based on tolerance) before AEA (R+AEA) to standard sequencing (AEA+R) in patients with refractory RAS WT mCRC. Patients are randomly assigned to receive R (Arm A) or AEA (with or without irinotecan, as determined by the investigator) (Arm B). Patients will be treated in a progressive manner until their disease progresses or intolerance develops. Patients must have had prior fluoropyrimidine, oxaliplatin, and irinotecan, and no prior AEA or R, as well as histologically confirmed mCRC, ECOG 2 and acceptable organ function. Patients must also have had prior fluoropyrimidine, oxaliplatin, and irinotecan, and no prior AEA or R. The main goal is to assess overall survival (OS) between evaluable patients (eligible, consented, and started protocol treatment) who were randomly assigned to R+AEA (arm A) or AEA+R (arm B) (arm B). We have 87 percent power to detect a change in median OS from 9 months to 14.5 months with 83 OS events, assuming a 1-sided significance level of 0.15 and an exponential distribution. A total of 124 patients were included in the study. Progression-free survival, objective response, and adverse events are all secondary goals. The study is scheduled to last three years in total. NCT04117945, NCT04117945, NCT04117945, NCT04117945, NCT04 Information about the clinical trial: 04117945.