Dr Eng on the Future Role for Targeted Therapy in mCRC

"We're finding that with a lot of our newest agents going further along in development…we want to try [and] move them forward so we can provide those options for our patients sooner and provide more selective therapy specific to their tumor type."

Cathy Eng, MD, FACP, FASCO, a professor of medicine and coleader of the Gastrointestinal Cancer Research Program at Vanderbilt-Ingram Cancer Center, discussed the evolution of targeted therapies and precision medicine in KRAS G12C–mutated metastatic colorectal cancer (mCRC).

Retrospective real-world data presented at the 2025 ESMO Gastrointestinal Cancers Congress highlighted that patients with KRAS G12C–mutated mCRC have somewhat worse outcomes than those with other KRAS mutations or wild-type disease. Although the median overall survival (OS) across the total study population was approximately 20.2 months, survival for patients harboring KRAS G12C was numerically shorter. Progression-free survival (PFS) trends followed a similar pattern, suggesting that the KRAS G12C alteration may carry prognostic implications and supports the continued development of precision-based approaches for this subgroup.

Eng noted that newer G12C-targeted agents are demonstrating encouraging activity in later-line settings. As a result, efforts are shifting toward advancing these agents earlier in the treatment sequence rather than reserving them solely for heavily pretreated disease. The goal is to offer patients individualized therapy sooner, maximizing potential benefit by aligning treatment with tumor biology.

Looking ahead, Eng stressed the importance of awareness and referral for clinical trial opportunities to accelerate progress in this space. Many promising KRAS G12C inhibitors and novel combinations (such as those targeting EGFR and SHP2, or immune checkpoint inhibitors) are being evaluated in ongoing studies. Earlier patient enrollment will be crucial to better understand optimal sequencing, resistance mechanisms, and long-term benefit of these precision therapeutics.

Although KRAS G12C–mutated mCRC continues to present a therapeutic challenge associated with worse survival outcomes, rapid innovation in targeted approaches and broader clinical trial participation hold the potential to reshape the future landscape of care for this patient population, she concludes.