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: Conca Veronica , Vetere Guglielmo , Moretto Roberto , Lonardi Sara , Antoniotti Carlotta , Germani Marco Maria , Pietrantonio Filippo , Bittoni Alessandro , Carullo Martina , Salvatore Lisa , Boccaccino Alessandra , Ronzoni Monica , Ricagno Gianmarco , Toma Ilaria , Cupini Samanta , Latiano Tiziana Pia , Arcangeli Giuseppina , Masi Gianluca , Fassan Matteo , Cremolini Chiara 
Published: June 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 .