Combination therapy of Adagrasib and Cetuximab in treating metastatic colorectal cancer with G12C KRAS mutation
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Reviewed by Dat Tien Nguyen, B.A, ScM.
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Posted on February 3rd, 2023
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KRAS is a major oncogene that contributes to the development of approximately half of all colorectal cancer cases. The glycine-to-cysteine mutation at amino acid position #12 (G12C) causes the KRAS protein to be stuck in its active form, leading to continuous signaling that can lead to cancerous development. This form of KRAS mutation is responsible for 3% - 4% of all colorectal cancer cases. Adagrasib is a small-molecule agent that can selectively bind to and inhibit G12C KRAS signaling. Thus, Adagrasib monotherapy is promising, but cancer cells can utilize signaling through the epidermal growth factor receptor (EGFR) pathway to reactivate G12C KRAS. The KRYSTAL-1 study had investigated the effectiveness of combining Adagrasib with an anti-EGFR monoclonal antibody, in the form of Cetuximab.
The study included 76 patients around the age of 60 who have metastatic colorectal cancer with mutant KRAS G12C. These patients had previously been treated with fluoropyrimidine-based chemotherapy in conjunction with either oxaliplatin, irinotecan, or both. 44 of them were assigned to take 1 capsule of 600 mg of Adagrasib, twice a day. The monotherapy lasted approximately 6 months and these patients were followed for 20 months. The other patients received a combination therapy of 1 capsule of 600 mg of Adagrasib, twice a day, in addition to weekly intravenous Cetuximab injection. Treatment lasted approximately 7 months and the follow-up period lasted 17.5 months. The rate of response is 17% in the monotherapy group; the addition of cetuximab significantly increased the response rate to 46%. In addition, the combination therapy group has a longer progression-free survival time of 6.9 months than the monotherapy group 5.6 months. In terms of safety, the rate of adverse events is higher in the monotherapy group, and the most common events are nausea, diarrhea, and vomiting.
The study included 76 patients around the age of 60 who have metastatic colorectal cancer with mutant KRAS G12C. These patients had previously been treated with fluoropyrimidine-based chemotherapy in conjunction with either oxaliplatin, irinotecan, or both. 44 of them were assigned to take 1 capsule of 600 mg of Adagrasib, twice a day. The monotherapy lasted approximately 6 months and these patients were followed for 20 months. The other patients received a combination therapy of 1 capsule of 600 mg of Adagrasib, twice a day, in addition to weekly intravenous Cetuximab injection. Treatment lasted approximately 7 months and the follow-up period lasted 17.5 months. The rate of response is 17% in the monotherapy group; the addition of cetuximab significantly increased the response rate to 46%. In addition, the combination therapy group has a longer progression-free survival time of 6.9 months than the monotherapy group 5.6 months. In terms of safety, the rate of adverse events is higher in the monotherapy group, and the most common events are nausea, diarrhea, and vomiting.