1. ctDNA-guided adjuvant treatment after radical-intent treatment of metastatic spread from colorectal cancer—the first interim results from the OPTIMISE study.
- Author
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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, and Spindler, Karen-Lise Garm
- Subjects
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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 - 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. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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