New Drug Combination Provides Hope for Treatment-Resistant Colon Cancer

A new innovative treatment approach has emerged for patients suffering from metastatic colorectal cancer with the KRAS G12C mutation, particularly those who have not responded to traditional chemotherapy. Researchers at City of Hope have conducted a Phase 3 clinical trial demonstrating that a combination therapy significantly improves patient outcomes.

Recently, the U.S. Food and Drug Administration (FDA) granted approval for this combination therapy to be used in treating patients whose KRAS G12C mutated colorectal cancer has progressed following chemotherapy. Findings from the trial were published in the Journal of Clinical Oncology, highlighting that patients who received a combination of the KRAS G12C inhibitor sotorasib and the monoclonal antibody panitumumab experienced a notably longer progression-free survival compared to those receiving standard treatment.

Dr. Marwan Fakih, a leading researcher at City of Hope, emphasized that this new therapeutic option extends disease control for patients and should be considered the new standard of care in this setting. The KRAS G12C mutation, which is present in approximately 10% of colorectal cancer cases, activates the KRAS protein, a key driver of tumor growth.

Sotorasib is the first FDA-approved inhibitor specifically targeting the KRAS G12C mutation, effectively binding to the mutated protein to block its activation and hinder cancer cell proliferation. Panitumumab, on the other hand, functions by targeting the epidermal growth factor receptor (EGFR), which is often overexpressed in colorectal cancer and contributes to cell growth and division.

This study builds on previous research indicating that combining sotorasib with panitumumab enhances the treatment's effectiveness. The ongoing trial, known as CodeBreaK 300, is pioneering in its comparative analysis of the sotorasib-panitumumab combination against existing treatment standards for patients with KRAS G12C-mutated colorectal cancer that has shown resistance to conventional therapies.

In this trial, 160 patients were distributed into three groups: one received a 960 mg dose of sotorasib along with panitumumab, the second received a lower 240 mg dose of sotorasib combined with panitumumab, and the third group was treated with either trifluridine/tipiracil or regorafenib, which represent current standard therapies.

Results indicated that the higher dose of sotorasib was associated with improved response rates and extended progression-free survival compared to the standard treatment group. Over 30% of patients in the high-dose sotorasib group achieved a significant reduction in tumor size, in contrast to just 1.9% in the standard treatment cohort. Although the trial was not primarily designed to assess overall survival, preliminary results suggested a potential 30% increase in overall survival for the high-dose group compared to standard care.

Dr. Fakih remarked on the promising response rates observed with this combination therapy, reinforcing the rationale for its use in earlier treatment lines for KRAS G12C metastatic colorectal cancer. The most common side effects reported included diarrhea, musculoskeletal pain, nausea, fatigue, liver toxicity, and cough. Further studies are underway to explore this combination as a first-line treatment option for this challenging cancer type.

For more detailed information, refer to the study by Filippo Pietrantonio et al., published in the Journal of Clinical Oncology.