Circulating tumor DNA (ctDNA) testing at 4 weeks post-surgery increases the prognostic value of BRAF and microsatellite status in patients with colorectal cancer (CRC), according to research presented at ASCO Breakthrough 2023.
Researchers found that, among patients with ctDNA-positive status, those with BRAF wild-type (BRAFwt) and microsatellite instability high (MSI-H) disease had the best outcomes.
Among patients with ctDNA-negative status, the best outcomes were seen in those with BRAFwt and MSI-H disease as well as those who had BRAFV600E mutations and MSI-H disease.
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These findings come from an analysis of data from the GALAXY study, which included 2083 patients with radically resected, stage II-IV CRC. The patients’ median age was 69 years, 54% were men, and 75% had left-sided tumors. Most patients had stage II (42%) or stage III (51%) disease, 43% had RAS mutations, 34% had received adjuvant chemotherapy, and 14% were ctDNA-positive at 4 weeks.
Most patients (n=1707) had BRAFwt and microsatellite-stable (MSS) disease, 110 had BRAFV600E mutations and MSI-H disease, 97 had BRAFwt and MSI-H disease, and 59 had BRAFV600E mutations and MSS disease.
Patients with BRAFwt/MSI-H disease were the youngest. Patients with BRAFV600E/MSI-H disease had the highest proportion of women, were most likely to have right-sided tumors, and were least likely to be ctDNA positive at 4 weeks.
The median follow-up was 496 days. Among patients with ctDNA-negative status at 4 weeks post-surgery, patients with BRAFwt/MSI-H disease or BRAFV600E/MSI-H disease had the best outcomes. The 18-month disease-free survival rate was:
- 100% for patients with BRAFwt/MSI-H disease (hazard ratio [HR], 0.09; 95% CI, 0.001-0.61; P =.006)
- 100% for patients with BRAFV600E/MSI-H disease (HR, 0.07; 95% CI, 0.001-0.50; P =.002)
- 93.3% for patients with BRAFwt/MSS disease (reference)
- 86.3% for patients with BRAFV600E/MSS disease (HR, 2.06; 95% CI, 0.84-4.23; P =.107).
Among patients with ctDNA-positive status at 4 weeks post-surgery, those with BRAFwt/MSI-H disease or BRAFwt/MSS disease had the best outcomes. The 18-month disease-free survival rate was:
- 66.7% for patients with BRAFwt/MSI-H disease (HR, 0.67; 95% CI, 0.21-2.20; P =.488)
- 0% for patients with BRAFV600E/MSI-H disease (HR, 7.54; 95% CI, 2.37-24.0; P <.001)
- 50.9% for patients with BRAFwt/MSS disease (reference)
- 33.3% for patients with BRAFV600E/MSS disease (HR, 2.33; 95% CI, 1.03-5.30; P =.043).
A multivariate analysis showed that several factors were significantly associated with inferior disease-free survival, including:
- ctDNA positivity at week 4 (HR, 11.68; 95% CI, 8.61-15.85; P <.001)
- Presence of RAS mutations (HR, 1.72; 95% CI, 1.26-2.36; P <.001)
- Presence of BRAF V600E mutations (HR, 2.05; 95% CI, 1.05-3.99; P =.035)
- De-differentiated tumors (HR, 2.04; 95% CI, 1.01-4.12; P =.047)
- Right-sided tumors (HR, 1.43; 95% CI, 1.02-2.01; P =.040).
Factors that were significantly associated with superior disease-free survival were:
- MSI-H disease (HR, 0.26; 95% CI, 0.10-0.62; P =.003)
- Female sex (HR, 0.69; 95% CI, 0.51-0.93; P =.016)
- Receipt of adjuvant therapy (HR, 0.69; 95% CI, 0.51-0.95; P =.022).
Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Reference
Watanabe J, Oki E, Kotani D, et al. Postoperative circulating tumor DNA-based molecular residual disease in patients with BRAF V600E and MSI-H colorectal cancer: Updated results from GALAXY study in the CIRCULATE-Japan. ASCO Breakthrough 2023. August 3-5, 2023. Abstract 32.
This article originally appeared on Cancer Therapy Advisor
