The emerging role of Sotorasib plus Panitumumab combination therapy in colorectal cancer treatment.

Abstract

Colorectal cancer (CRC) poses a substantial global health challenge, ranking as the third most commonly diagnosed and second most fatal cancer worldwide. With an increasing incidence, particularly in older populations, CRC demands innovative therapeutic approaches to address the limitations of existing treatments. One critical target in CRC is the KRAS gene, which is frequently mutated and implicated in various cancer-related processes. This narrative review explores the promising role of Sotorasib plus Panitumumab combination therapy in CRC treatment. Combining Sotorasib with Panitumumab, an EGFR antagonist, offers a synergistic approach to comprehensively block KRAS and EGFR pathways, potentially overcoming resistance mechanisms observed in monotherapies. The review discusses the evolution of CRC treatment from traditional chemotherapy to the advent of targeted therapies like Bevacizumab and Cetuximab. It highlights the limitations of existing therapies, including resistance and toxicities, emphasising the urgency for innovative approaches. The CodeBreak clinical trials, specifically CodeBreak 101 and CodeBreak 300, provide a focal point for evaluating the efficacy of Sotorasib plus Panitumumab in patients with refractory KRAS G12C-mutated mCRC. Preliminary results demonstrate significant improvements in progression-free survival (PFS) and objective response rates, suggesting a paradigm shift in CRC treatment. The preliminary findings from the CodeBreak 300 trial signify a transformative impact of Sotorasib plus Panitumumab in refractory KRAS G12C-mutated mCRC. With a notable increase in PFS and objective response rates and a well-tolerated safety profile, this combination therapy emerges as a potential new standard of care. The results present an optimistic outlook for patients resistant to conventional therapies.