KEY TAKEAWAYS
- The phase 2 OPTIMISE study evaluated the effectiveness of using circulating tumor DNA (ctDNA) to guide adjuvant chemotherapy (aCTh) decisions for patients who’ve undergone radical treatment for metastatic colorectal cancer (mCRC).
- In the ctDNA-guided group, 19% displayed positive ctDNA results. These patients were suitable for intensive, multi-agent chemotherapy.
- ctDNA analyses were consistently reliable, with results typically available within three workdays.
Circulating tumor DNA (ctDNA) presence post-radical treatment for metastatic colorectal cancer (mCRC) signifies a heightened risk of recurrence. A ctDNA-informed adjuvant chemotherapy (aCTh) approach might mitigate this risk. While ctDNA-driven aCTh has demonstrated reduced chemotherapy use without compromising results in early-stage CRC, the OPTIMISE study aimed to evaluate its efficacy following radical treatment for mCRC. This interim analysis focused on the study’s feasibility, allowing for potential modifications ahead of a larger phase II trial.
This study is a randomized, open-label trial contrasting ctDNA-driven aCTh with the standard of care (SOC). Plasma ctDNA analyses utilized ddPCR to detect CRC-specific alterations and NPY gene methylation. Eligibility criteria included undergoing radical treatment for mCRC and clinical suitability for triple-agent chemotherapy. Pre-randomization, patients (pts) received a PET/CT scan. Those in the standard arm received SOC, while those in the ctDNA-driven arm had treatment guided by ctDNA presence. Feasibility targets encompassed the enrollment of 30 participants across two Danish facilities within 12 months, a randomization adherence above 80%, and a less than 20% incidence of unexpected PET-CT findings.
A total of 32 pts were enrolled. Unexpected PET-CT findings occurred in 22% of the subjects. Among these, five underwent radical treatment followed by randomization. Overall, 97% of eligible pts underwent randomization. Fourteen pts received SOC, and sixteen were given ctDNA-guided adjuvant treatment and follow-up. All baseline ctDNA analyses met quality standards, with results available in a median of three workdays. Among the ctDNA-informed group, 19% displayed positive ctDNA findings, all qualifying for multi-agent chemotherapy. The average time between study entry and aCTh commencement was 22 days, with the study-specific PET/CT scan being the primary reason for the delay.
Given its pioneering nature, early feasibility verification of the study was paramount. The study met its feasibility objectives despite the limited participant number introducing estimate variability. Analytical quality and turnaround were satisfactory. Only ctDNA-positive subjects in the experimental cohort will receive a PET/CT scan to minimize treatment onset delays. The study has been viable and will proceed to its next phase with this optimized study flow.
Source: https://www.annalsofoncology.org/article/S0923-7534(23)00632-4/fulltext
Clinical Trial: https://classic.clinicaltrials.gov/ct2/show/NCT04680260
Callesen, L., Hansen, T., Andersen, R., Pallisgaard, N., Kramer, S., Schlander, S., Rafaelsen, S., Boysen, A., Jensen, L., Jakobsen, A., Spindler, K. CTDNA-GUIDED ADJUVANT TREATMENT AFTER RADICAL INTENT TREATMENT OF METASTATIC SPREAD FROM COLORECTAL CANCER IS FEASIBLE – RESULTS FROM THE PREPLANNED INTERIM ANALYSIS OF THE OPTIMISE STUDY. https://doi.org/10.1016/j.annonc.2023.04.490
