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- Title
ctDNA-guided adjuvant treatment after radical-intent treatment of metastatic spread from colorectal cancer—the first interim results from the OPTIMISE study.
- Authors
Callesen, Louise Bach; Hansen, Torben Frøstrup; Andersen, Rikke Fredslund; Pallisgaard, Niels; Kramer, Stine; Schlander, Sven; Rafaelsen, Søren Rafael; Boysen, Anders Kindberg; Jensen, Lars Henrik; Jakobsen, Anders; Spindler, Karen-Lise Garm
- Abstract
Patients with detectable ctDNA after radical-intent treatment of metastatic spread from colorectal cancer (mCRC) have a very high risk of recurrence, which may be prevented with intensified adjuvant chemotherapy (aCTh). In the OPTIMISE study, we investigate ctDNA-guided aCTh after radical-intent treatment of mCRC. Here we present results from the preplanned interim analysis. The study is an open-label 1:1 randomized clinical trial comparing ctDNA-guided aCTh against standard of care (SOC), with a run-in phase investigating feasibility measures. Key inclusion criteria; radical-intent treatment for mCRC and clinically eligible for triple-agent chemotherapy. Patients underwent a PET-CT scan before randomization. ctDNA analyses of plasma samples were done by ddPCR, detecting CRC-specific mutations and methylation of the NPY gene. In the ctDNA-guided arm, ctDNA positivity led to an escalation strategy with triple-agent chemotherapy, and conversely ctDNA negativity led to a de-escalation strategy by shared-decision making. Patients randomized to the standard arm were treated according to SOC. Feasibility measures for the run-in phase were; the inclusion of 30 patients over 12 months in two Danish hospitals, compliance with randomization >80%, rate of PET-CT-positive findings <20%, and eligibility for triple-agent chemotherapy >80%. Thirty-two patients were included. The rate of PET-CT-positive cases was 22% (n = 7/32). Ninety-seven percent of the patients were randomized. Fourteen patients were randomly assigned to SOC and sixteen to ctDNA-guided adjuvant treatment and follow-up. All analyses of baseline plasma samples in the ctDNA-guided arm passed the quality control, and 19% were ctDNA positive. The median time to result was three working days. All ctDNA-positive patients were eligible for triple-agent chemotherapy. The study was proven to be feasible and continues in the planned large-scale phase II trial. Results from the OPTIMISE study will potentially optimize the adjuvant treatment of patients undergoing radical-intent treatment of mCRC, thereby improving survival and reducing chemotherapy-related toxicity.
- Subjects
DENMARK; THERAPEUTIC use of antineoplastic agents; ADJUVANT chemotherapy; DRUG efficacy; PILOT projects; PRIVACY; RESEARCH; DNA; GENETIC mutation; ACADEMIC medical centers; METASTASIS; POSITRON emission tomography computed tomography; COLORECTAL cancer; CANCER patients; COMPARATIVE studies; RANDOMIZED controlled trials; DNA methylation; DESCRIPTIVE statistics; MEDICAL ethics; DECISION making; RESEARCH funding; EXTRACELLULAR space; STATISTICAL sampling; TUMOR markers; NUCLEIC acids; LONGITUDINAL method; BLOOD; EVALUATION
- Publication
Acta Oncologica, 2023, Vol 62, Issue 12, p1742
- ISSN
0284-186X
- Publication type
Article
- DOI
10.1080/0284186X.2023.2259083