What type of study is this?

This is a Phase 2 study (also classified as: Pre-Registered Trial).

August 17, 2025

Circulating tumour DNA-guided second-line targeted therapy for patients with metastatic colorectal cancer after failure of first-line cetuximab-based treatment: A prospective, phase II trial

Key Points

Objective response rate reached 45.8% among patients receiving ctDNA-guided therapies, showing potential effectiveness.
Median progression-free survival was 10.2 months, while median overall survival was noted at 24.9 months, indicating significant treatment duration.
In this phase II trial, patients treated with bevacizumab had an overall response rate of 40.0%, while cetuximab showed an ORR of 44.4%.
No severe adverse events were reported, suggesting a favorable safety profile for ctDNA-guided targeted therapies.

Abstract

Abstract Background The genetic profile of metastatic colorectal cancer (mCRC) can dynamically change after treatment with cetuximab. This study prospectively evaluated the efficacy of second-line targeted therapies according to the molecular characteristics of circulating tumour DNA (ctDNA) in mCRC patients. Methods This phase II trial included mCRC patients who failed after cetuximab-based first-line treatment. CtDNA analysis was performed to guide second-line targeted therapies. The primary endpoint was the objective response rate (ORR). Secondary endpoints included disease control rate (DCR), progression-free survival (PFS), overall survival (OS), as well as safety and tolerability. Results Between April 8, 2021, and December 11, 2022, 24 patients were enrolled; 50% were males, and the median age was 57 years. Treatment regimens included bevacizumab (58.3%), cetuximab (37.5%), and a combination of trastuzumab and pyrotinib (4.2%). KRAS mutations were present in 12.5% of patients, whereas BRAF mutations were not detected. HER2 amplification occurred in 4.2% of the patients. The ORR for all patients was 45.8%, and the DCR was 87.5%. The median PFS was 10.2 months, and the median OS was 24.9 months. For RAS/BRAF wild-type patients who received bevacizumab, the ORR was 40.0%, and the DCR was 90.0%. For those receiving cetuximab, the ORR was 44.4%, and the DCR was 77.7%. The mPFS was 12.6 months and 7.4 months for patients who received bevacizumab or cetuximab, respectively (p = 0.854). The median OS was 27.1 months and 19.9 months for the bevacizumab and cetuximab groups, respectively (p = 0.417). In addition, no grade 4 or 5 treatment-related adverse events were reported. Conclusions CtDNA is a promising biomarker for guiding second-line treatment decisions in mCRC patients. For patients with a continuous RAS/BRAF wild-type status, bevacizumab-based second-line treatment might be more advantageous than cetuximab-based treatment. ClinicalTrials.gov Identifier: This study was registered on ClinicalTrials.gov with NCT04831528 (https://clinicaltrials.gov/search?term=NCT04831528). Trial registration: www.clinicaltrials.gov (NCT04831528).

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