In an analysis from the French SAMCO-PRODIGE 54 trial reported in JAMA Oncology, Taïeb et al examined survival outcomes associated with a change in ctDNA from baseline to 1 month after start of treatment in patients receiving ICI treatment with avelumab for deficient mismatch repair/microsatellite instability–high (dMMR/MSI-H) metastatic colorectal cancer (mCRC).
Study Details
In the trial, patients were randomly assigned to receive avelumab or standard chemotherapy, with or without a targeted agent. The purpose of the current analysis was to determine the association of clinical outcomes with ctDNA level at baseline (pretreatment) and with change in ctDNA level from baseline to 1 month after start of treatment. Favorable ctDNA responders were defined as those with ctDNA reduction equal to the median or greater; poor ctDNA responders were those with a reduction less than the median.
Key Findings
A total of 99 patients had ctDNA data available at baseline, with 74 of these also having data available at 1 month after starting treatment.
Among the patients with available baseline ctDNA, baseline ctDNA positivity or concentration were not associated with clinical outcomes.
Patients with poor vs favorable ctDNA response had significantly poorer progression-free survival (hazard ratio [HR] = 2.98, 95% confidence interval [CI] = 1.77–5.01, P < .001) and overall survival (HR = 3.61, 95% CI = 1.81–7.17, P < .001). The association was stronger for progression-free survival (HR = 4.22, 95% CI = 1.77–10.1, P = .001) and overall survival (HR = 17.40, 95% CI = 3.82–79.70, P < .001) among patients receiving avelumab than among patients receiving chemotherapy (progression-free survival HR = 2.09, 95% CI = 1.03–4.21, P = .04; overall survival HR = 1.51, 95% CI = 0.61–3.72, P = .38).
Avelumab significantly improved progression-free survival vs chemotherapy among favorable ctDNA responders (HR = 0.33, 95% CI = 0.14–0.77, P = .008) but not among poor ctDNA responders (HR = 1.32, 95% CI = 0.67–2.62, P = .42).
In multivariable analysis, lack of ctDNA response was associated with significantly increased risk of disease progression or death in patients receiving avelumab (HR = 7.27, 95% CI = 2.23–23.7, P = .001) but not in patients receiving chemotherapy (HR = 1.61, 95% CI = 0.66–3.93, P = .30).
The investigators concluded: “The findings of this secondary analysis of [this trial] found that change in ctDNA at 1-month posttreatment can predict long-term outcomes in patients with dMMR/MSI-H mCRC treated with ICIs.”
Julien Taïeb, MD, PhD, of Assistance Publique Hopitaux de Paris, Universite Paris, is the corresponding author for the JAMA Oncology article.
Disclosure: The study was supported by Merck KGAa, Fédération Francophone de Cancérologie digestive, and others. For full disclosures of all study authors, visit jamanetwork.com.
