ctDNA changes as biomarker for pembrolizumab response in advanced urothelial carcinoma

An exploratory analysis of circulating tumour DNA (ctDNA) samples from KEYNOTE-361 participants demonstrated that ctDNA dynamics can be influenced by the treatment mechanism.

Previously, the KEYNOTE-361 trial (NCT02853305) did not show any benefit of first-line pembrolizumab over chemotherapy in patients with advanced urothelial carcinoma [1]. To potential predictive biomarkers, a retrospective, exploratory analysis of pre- and post-treatment ctDNA was performed in a subset of participants who received pembrolizumab (n=130) or chemotherapy (n=130) in KEYNOTE-361. Prof. Thomas Powles (Barts Cancer Institute, UK) presented the results [2].

Baseline ctDNA levels and early dynamics were associated with overall response, progression-free survival, and overall survival in the pembrolizumab arm but not in the chemotherapy arm. Chemotherapy induced larger ctDNA decreases (including ctDNA clearance) from baseline to treatment cycle 2 than pembrolizumab.

“These results suggest distinct patterns in early ctDNA changes with immunotherapy and chemotherapy and differences in their association with long-term outcomes,” Prof. Powles concluded. “This provides preliminary insights into the utility of liquid biopsies for treatment monitoring in metastatic urothelial cancer.”

1. Powles T, et al. Lancet Oncol. 2021;22:931-945.
2. Powles T, et al. Quantitative circulating tumor DNA (ctDNA) assessment in patients (pts) with advanced urothelial carcinoma (UC) treated with pembrolizumab (pembro) or platinum-based chemotherapy (chemo) from the phase 3 KEYNOTE-361 trial. Abstract 4518, ASCO Annual Meeting 2024, 31 May–4 June, Chicago, IL, USA.

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Posted on 18 July 202418 July 2024