Late-line Systemic Therapy in Metastatic Colorectal Cancer: A Narrative Review and Australian Expert Perspective

Area of Science:

• Oncology
• Medical Genetics

Background:

• Metastatic colorectal cancer (mCRC) presents significant challenges, especially in patients with disease progression after extensive prior treatments.
• The therapeutic landscape for mCRC is evolving due to molecular profiling advancements, leading to personalized treatment strategies.

Purpose of the Study:

• To review current evidence for third- and later-line therapies in mCRC.
• To discuss practical considerations for treatment sequencing and propose potential treatment algorithms for refractory mCRC.

Main Methods:

• Comprehensive literature review of contemporary evidence and key clinical trial data.
• Analysis of targeted therapies based on specific molecular alterations (e.g., BRAF, HER2, KRAS G12C).
• Evaluation of agents like trifluridine/tipiracil, regorafenib, and fruquintinib for heavily pretreated patients.

Main Results:

• Targeted therapies are increasingly used across different lines of therapy based on tumor molecular profiling.
• Specific agents demonstrate benefit in heavily pretreated mCRC patients.
• Broad molecular testing, including rare biomarkers, aids individualized management.

Conclusions:

• Despite therapeutic advances, prognosis for late-line mCRC remains poor, highlighting the need for continued research and clinical trial enrollment.
• Multidisciplinary collaboration is crucial for optimizing patient selection and therapy sequencing as new treatments emerge.
• Novel agents are expected to refine management strategies and improve outcomes in refractory mCRC.