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It is critical to identify novel therapeutic options following disease progression on first- and second-line chemotherapy such as fluoropyrimidine and oxaliplatin.
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Treatment Combo Outperforms Standard-of-Care in Colorectal Cancer Trial

The novel therapeutic could provide a new option for patients with treatment-resistant KRAS gene mutation-positive colorectal cancer

City of Hope
Published:Oct 30, 2023
|2 min read
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An international Phase 3 clinical trial found that metastatic colorectal cancer patients with a rare genetic tumor mutation, KRAS G12C, experienced superior progression-free survival rates compared to standard of care when offered a combination treatment of KRAS gene inhibitor sotorasib and monoclonal antibody panitumumab. Findings of the study were published recently in The New England Journal of Medicine.

Standard chemotherapies often fail to control or eliminate the disease for patients with the KRAS G12C mutation, which is associated with a worse outcome. So, it is important to identify novel therapeutic options following disease progression on first- and second-line chemotherapy such as fluoropyrimidine, oxaliplatin, and irinotecan.

“This is the first Phase 3 clinical trial to show a benefit over standard-of-care in patients with the KRAS G12C mutation whose cancer progressed after receiving standard chemotherapy. The efficacy results from our study are promising in this population with unmet needs and should set a new standard of care for metastatic colorectal cancer patients with KRAS G12C mutation who progressed following prior standard treatments,” said Marwan Fakih, MD, professor in the Department of Medical Oncology & Therapeutics Research and the Judy & Bernard Briskin Distinguished Director of clinical research at City of Hope. Fakih is the lead author of the new study and principal investigator of the clinical trial.

Evaluating sotorasib–panitumumab duo in Phase 3 trial

Building on positive results from a Phase 2 trial that evaluated sotorasib in combination with panitumumab, an antibody targeting epidermal growth factor receptor, the Phase 3 trial evaluated the same duo and tested sotorasib at two different doses. Participants in the randomized trial, all of whom had progressed on standard chemotherapy, were given either 240 mg of sotorasib with panitumumab, 960 milligrams of sotorasib with panitumumab, or standard-of-care therapy with anticancer medications (either a combination of trifluridine–tipiracil or regorafenib).

Both the lower and higher doses of sotorasib in combination with panitumumab met the goals of the study by achieving superior progression-free survival over the other anticancer medications. The higher dose regimen was particularly effective, more than doubling the median time to progression compared to standard-of-care, Fakih reported. Additionally, a far larger number of patients under the higher dose regimen showed major disease regression, “with a response rate of 26.4 percent versus zero,” he added. 

“While this study sets a new standard following progression on standard chemotherapy, additional studies will interrogate the value of this regimen when combined with standard chemotherapy in earlier treatment settings in patients with metastatic KRAS G12C mutated colorectal cancer,” Fakih said. “In addition, ongoing biomarker work will help better define mechanisms of resistance to this targeted combination and how to overcome such challenges.”

- This press release was originally published on the City of Hope website