The treatment landscape for metastatic colorectal cancer (mCRC) has undergone significant evolution, with real-world evidence now demonstrating substantial improvements in patient outcomes. Recent data presented at ESMO 2023 highlights the impact of strategic treatment sequencing and the expanding role of targeted therapies.
Real-World Evidence Shows Extended Survival
The PROMETCO trial, a comprehensive real-world study spanning 18 countries and including 738 patients, has revealed remarkable progress in patient survival. The study demonstrated an overall survival of 35.4 months for patients receiving multiple lines of therapy, a significant improvement from the historical survival rate of approximately 20 months. Nearly 80% of patients received VEGF inhibitors, while 40% received anti-EGFR therapy.
Strategic Treatment Sequencing
A large-scale retrospective analysis of 866 patients has provided valuable insights into the optimal sequencing of later-line treatments. The study compared different treatment sequences involving regorafenib and TAS-102, revealing potential advantages to initiating treatment with regorafenib followed by TAS-102. This sequence showed improved toxicity profiles, with lower rates of neutropenia (under 40% versus 50%) and reduced need for G-CSF support (14% versus 18%).
Emerging Role of VEGF Inhibition
The treatment paradigm continues to emphasize the importance of VEGF inhibition, even in later lines of therapy. The recently approved fruquintinib, a highly selective VEGF receptor inhibitor, has demonstrated significant efficacy in the FRESCO-2 trial. The study showed notable progression-free survival benefits in patients who had previously received standard therapies, including TAS-102 and regorafenib.
Personalized Treatment Approaches
Dr. Tanios Bekaii-Saab of Mayo Clinic emphasizes the importance of molecular profiling, noting that 15-20% of mCRC patients harbor targetable alterations. This has led to the implementation of precision medicine strategies, including the use of liquid biopsy ctDNA assessment to guide treatment decisions within the first week of diagnosis.
Cost-Effectiveness Considerations
Recent analysis published in Clinical Colorectal Cancer evaluated various treatment strategies using a Markov model to assess cost-effectiveness. The study particularly highlighted the advantages of dose-optimized regorafenib in terms of benefit-to-toxicity ratio and cost-effectiveness measures, providing important insights for treatment selection in resource-conscious healthcare environments.
Future Directions
The expanding therapeutic landscape, including new targeted options and combination strategies, continues to evolve. The success of VEGF inhibition across multiple treatment lines, demonstrated by agents such as regorafenib, fruquintinib, and TAS-102 plus bevacizumab, underscores the continuing importance of this therapeutic approach in mCRC management.
