4.5 Review

Ongoing and evolving clinical trials enhancing future colorectal cancer treatment strategies

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Informing metastatic colorectal cancer patients by quantifying multiple scenarios for survival time based on real-life data

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Summary: Although reported median overall survival in metastatic colorectal cancer patients participating in systemic therapy trials has increased, it is uncertain whether these results translate to real-life populations. Improvement in survival was observed in some patients receiving systemic therapy, but overall, there was no significant increase in median overall survival in the total population.

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Summary: Studies have shown that postoperative ctDNA analysis is prognostically significant in nonmetastatic CRC patients, with higher predictive accuracy for recurrence compared to clinicopathologic risk factors, and increasing mutant allele frequency (MAF) further stratifying recurrence risk.

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Jenny F. Seligmann et al.

Summary: In the FOCUS4 trial, adavosertib showed potential as a well-tolerated therapy for RAS/TP53-mutant mCRC, with significant improvement in progression-free survival (PFS) compared to active monitoring (AM). However, there was no significant improvement in overall survival (OS), and the activity of adavosertib was higher in left-sided tumors compared to right-sided tumors. Further testing is needed in this population with unmet needs.

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Encorafenib Plus Cetuximab as a New Standard of Care for Previously Treated BRAF V600E-Mutant Metastatic Colorectal Cancer: Updated Survival Results and Subgroup Analyses from the BEACON Study

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Summary: The study evaluated different treatment regimens for patients with BRAF V600E-mutant metastatic colorectal cancer, showing that encorafenib plus cetuximab improved overall survival, objective response rate, and progression-free survival compared to standard chemotherapy.

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Minimal Residual Disease Detection using a Plasma-only Circulating Tumor DNA Assay in Patients with Colorectal Cancer

Aparna R. Parikh et al.

Summary: The study demonstrates that detection of persistent circulating tumor DNA in plasma shows favorable sensitivity and specificity for predicting recurrence after curative-intent surgery for colorectal cancer. Integrating analysis of genomic and epigenomic signatures enhances the accuracy of detection, supporting the potential clinical utility of plasma-only ctDNA minimal residual disease detection.

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Rathin Gosavi et al.

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Summary: This study aimed to investigate the antitumour activity and safety of trastuzurnab deruxtecan in patients with HER2-expressing metastatic colorectal cancer. The drug showed promising and durable activity in HER2-positive metastatic colorectal cancer refractory to standard treatment, with a safety profile consistent with previous trials. However, careful monitoring and prompt intervention are required for important risks like interstitial lung disease and pneumonitis.

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Noritaka Tanaka et al.

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ctDNA to Guide Adjuvant Therapy in Localized Colorectal Cancer (CRC)

Laura Masfarre et al.

Summary: Detection of minimal residual disease (MRD) through circulating tumor DNA (ctDNA) has emerged as a powerful prognostic biomarker for identifying patients at higher risk of recurrence following surgery for localized colorectal cancer (CRC). Clinical trials are ongoing to evaluate the impact of ctDNA-guided treatment on improving clinical outcomes for CRC patients.

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BRAF, MEK and EGFR inhibition as treatment strategies in BRAF V600E metastatic colorectal cancer

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Summary: The development of therapeutic strategies targeting MAPK/ERK and EGFR signaling in BRAF V600E mutated mCRC, with drugs like encorafenib, binimetinib, and cetuximab, has proven successful in improving clinical outcomes. The BEACON trial using these drugs has established a new standard of care in previously treated BRAF V600E mutant mCRC patients, showing impressive improvement in outcomes and tolerable toxicity compared to chemotherapy.

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Circulating Tumor Cells Versus Circulating Tumor DNA in Colorectal Cancer: Pros and Cons

Carlyn Rose C. Tan et al.

CURRENT COLORECTAL CANCER REPORTS (2016)

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Neoadjuvant chemotherapy in locally advanced colon cancer. A phase II trial

Anders Jakobsen et al.

ACTA ONCOLOGICA (2015)

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Chromosomal rearrangements involving the NTRK1 gene in colorectal carcinoma

Laurent Creancier et al.

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