Personalized circulating tumor DNA (ctDNA) monitoring can predict outcomes during and after treatment in patients with advanced melanoma, according to research published in Cancer.
Researchers found that ctDNA status could predict distant metastasis-free survival (DMFS) and progression-free survival (PFS) during and after treatment with immune checkpoint inhibitors (ICIs).
The researchers used a personalized, tumor‐informed ctDNA assay on 555 prospectively collected plasma samples from 69 patients with advanced melanoma. The patients were divided into 3 cohorts.
Cohort A
Cohort A included 30 patients with stage III disease who were receiving adjuvant anti-PD-1 therapy or undergoing observation. In this group, ctDNA positivity at week 4 and week 6 of adjuvant treatment was associated with inferior DMFS.
The median DMFS was 11.5 months for patients who were ctDNA positive at week 4 and was not reached for patients who were ctDNA negative at that time (hazard ratio [HR], 6.9, P =.025).
The median DMFS was 3.5 months for patients who were ctDNA positive at week 6 and not reached for patients who were ctDNA negative at that point (HR, 34.54, P <.0001).
Cohort B
Cohort B included 29 patients with unresectable stage III/IV disease who were receiving frontline PD-1 inhibitor-based treatment.
In this group, ctDNA positivity at weeks 3-11 of first‐line treatment was associated with worse PFS (P =.015). Patients with an increase in ctDNA levels at 3-11 weeks had significantly shorter PFS than patients who had a decrease in ctDNA levels. The median PFS was 5.7 months and not reached, respectively (HR, 22; P =.006).
In addition, patients who had increasing ctDNA levels at 6 weeks had significantly shorter PFS than patients with decreasing and/or undetectable ctDNA at that time point. The median PFS was 7.5 months and not reached, respectively (HR, 18; P =.013).
Both clinical trials were funded by Sanofi, the pharmaceutical company that created fitusiran.
Cohort C
Cohort C included 10 patients with stage III/IV disease who had completed ICI therapy and were undergoing surveillance. Results in this group suggested that undetectable ctDNA after ICI treatment is associated with favorable outcomes.
Nine of the 10 patients were ctDNA negative at enrollment. Seven patients were still ctDNA negative and free of progression at a median follow‐up of 14.67 months.
Of the 3 ctDNA‐positive patients, 2 had disease progression and 1 died from recurrence soon after the positive ctDNA result. ctDNA positivity preceded clinical progression by a median of 3.34 months. The 2 patients who were still alive responded to subsequent therapy.
“Personalized and tumor-informed longitudinal ctDNA monitoring is a valuable prognostic and predictive tool that may be used throughout the clinical course of patients with advanced melanoma,” the researchers concluded.
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
Eroglu Z, Krinshpun S, Kalashnikova E, et al.
Circulating tumor DNA‐based molecular residual disease detection for treatment monitoring in advanced melanoma
patients. Cancer. Published online March 4, 2023. doi:10.1002/cncr.34716
Circulating tumor DNA‐based molecular residual disease detection for treatment monitoring in advanced melanoma
patients. Cancer. Published online March 4, 2023. doi:10.1002/cncr.34716
Originally posted in HealthDay.
