Innovative Drug Combination Shows Promise for Refractory Colon Cancer Patients

A groundbreaking phase 3 clinical trial conducted by researchers at City of Hope has revealed a new combination therapy that significantly improves outcomes for patients with metastatic colorectal cancer harboring the KRAS G12C mutation, especially those who have ceased responding to standard chemotherapy treatments. This promising development has led to批准 by the U.S. Food and Drug Administration (FDA) in January for treating adults with metastatic KRAS G12C-mutated colorectal cancer that has progressed despite previous therapies.

The study, published in the Journal of Clinical Oncology, focused on comparing the efficacy of combining sotorasib, a small-molecule inhibitor targeting the KRAS G12C mutation, with panitumumab, an anti-EGFR monoclonal antibody, against standard care options. Results demonstrated that patients receiving the sotorasib-panitumumab combination experienced notably longer progression-free survival. Moreover, there was a strong trend toward increased overall survival, indicating a potential shift in treatment standards.

KRAS mutations, present in up to 45% of colorectal cancer cases, are known to activate proteins that drive tumor growth. However, the G12C mutation is less common, found in fewer than 10% of these cases. Sotorasib specifically targets this mutation by binding to the mutant KRAS G12C protein, effectively preventing its activation and subsequent tumor proliferation.

The trial involved 160 patients, divided into three groups: one received a high dose of sotorasib (960 mg) combined with panitumumab; another received a lower dose (240 mg) with panitumumab; and the third received current standard therapies such as trifluridine/tipiracil or regorafenib. The high-dose group showed a more than 30% objective response rate, a significant improvement compared to just 1.9% in the standard care arm.

While the study was not primarily designed to assess overall survival, preliminary data suggested a 30% prolongation in survival for the high-dose group. Common adverse effects included diarrhea, nausea, fatigue, and musculoskeletal pain, which were manageable in the clinical setting. Ongoing studies are exploring the potential of this combination as a first-line therapy.

Dr. Marwan Fakih, senior author of the study, emphasized that these findings could establish a new standard of care and offer renewed hope to patients with limited treatment options. The trial, known as CodeBreaK 300, marks the first head-to-head comparison of sotorasib plus panitumumab versus existing therapies in this patient subset.

City of Hope continues to collaborate with biopharmaceutical companies to advance targeted cancer therapies, aiming to improve quality of life and survival rates for colorectal cancer patients worldwide.