Use of circulating tumor DNA (ctDNA) to affect the adjuvant or post-adjuvant treatment of patients with stage III and high-risk stage II resected colon cancer: The ERASE-CRC project by GONO.
Authors: Veronica Conca, Guglielmo Vetere, Roberto Moretto, Sara Lonardi, Carlotta Antoniotti, Marco Maria Germani, Filippo Pietrantonio, Alessandro Bittoni, Martina Carullo, Lisa Salvatore, Alessandra Boccaccino, Monica Ronzoni, Gianmarco Ricagno, Ilaria Toma, Samanta Cupini, Tiziana Pia Latiano, Giuseppina Arcangeli, Gianluca Masi, Matteo Fassan, Chiara Cremolini
Journal: Journal of Clinical Oncology (2024)

TPS3644 Background: Three or 6 months of fluoropyrimidines plus oxaliplatin is the standard adjuvant therapy for stage III and high-risk stage II colon cancer, but 20-25% of patients relapse. CtDNA is a promising biomarker of minimal residual disease (MRD) after primary tumor resection and a potential guide in the adjuvant treatment decision-making process. Indeed, ctDNA-positivity after surgery or at the end of adjuvant therapy is associated with higher risk of recurrence. Intensifying the adjuvant and/or the post-adjuvant treatment could be a valuable strategy in these cases. CtDNA clearance has been suggested as a predictor of long-term clinical outcome. Methods: ERASE-CRC is a prospective, open-label, multicentre study, including three phase 2 trials enrolling ctDNA-positive patients with radically resected stage III or high-risk stage II (one major prognostic factor or at least two minor prognostic factors) adenocarcinoma of the colon or intraperitoneal rectum. CtDNA is centrally assessed through a tissue-informed method, F1Tracker. In the phase II ERASE-CRC Part 1 study, patients that are ctDNA-positive after surgery (2-6 weeks) are randomized 1:1 to 6 months of either FOLFOX or CAPOX at investigators’ choice (standard arm) versus FOLFOXIRI (experimental arm). In the phase II single arm ERASE-HER2 study, ctDNA-positive patients with HER2 amplified and RAS wild-type tumors received FOLFOX plus trastuzumab and tucatinib for 12 cycles. In the phase II ERASE-CRC Part 2 study, ctDNA-positive patients after the end of an oxaliplatin-based adjuvant therapy (either in the context or outside ERASE-CRC Part 1 or ERASE-HER2) are randomized 1:2 to observation (standard arm) or trifluridine/tipiracil for 6 cycles (experimental arm). The primary endpoint is the clearance rate of ctDNA after the adjuvant (ERASE-CRC Part 1 and ERASE-HER2) or the post-adjuvant treatment (ERASE-CRC Part 2). 300 patients will be randomized in ERASE-CRC Part 1 to detect a 15% difference in ctDNA clearance rate between the experimental and the standard arm with expected clearance rates of 65% and 50%, respectively, and 1-sided alpha and beta errors of 0.05 and 0.2, respectively. 18 patients will be enrolled in ERASE-HER2 to observe a ctDNA clearance rate of 80% with the targeted treatment ( versus 50% expected), and ctDNA clearance should be observed in 13 cases to consider the strategy promising. Finally, 159 patients will be randomized in ERASE-CRC Part 2 to detect a 15% difference in ctDNA clearance rate between the experimental and the standard arm with 20% and 5% expected clearance rates respectively, and 1-sided alpha and beta errors of 0.05 and 0.2, respectively. Approximately 40 Italian Oncology Units are participating in the study. Currently, 19 and 8 patients have been randomized in ERASE-CRC Part 1 or 2, respectively. NCT05062889. Clinical trial information: NCT05062889 .