Circulating tumor DNA-guided de-escalation or escalation of adjuvant therapy in high-risk stage II and stage III colon cancer: the phase 2 PEGASUS trial.

Circulating tumor DNA-guided treatment in high-risk stage II and III colon cancer achieved a 2-year relapse-free rate of 88% among ctDNA-negative patients, but did not meet the predefined threshold.

• Why it matters: Accurate risk stratification is crucial to optimize adjuvant therapy in colon cancer, reducing unnecessary toxicity for low-risk patients and improving outcomes for high-risk ones.
• What they did: The phase 2 PEGASUS trial enrolled 135 patients, using ctDNA status post-surgery to guide therapy: ctDNA-positive patients received escalating chemotherapy, while ctDNA-negative patients received capecitabine, with primary endpoint assessing 2-year relapse-free rate among ctDNA-negative patients.
• The result: The study found a 2-year relapse-free rate of 88% in ctDNA-negative patients, below the 92% threshold, and observed similar disease-free survival compared to controls but with less neurotoxicity, indicating potential for operational clinical use but the need for further trials.