Clinical utility of plasma ctDNA sequencing in metastatic urothelial cancer

尿路上皮癌 医学 肿瘤科 癌症 癌症研究 内科学 膀胱癌
作者
Clara Helal,Cédric Pobel,Arnaud Bayle,Damien Vasseur,Claudio Nicotra,Félix Blanc-Durand,Natacha Naoun,Alice Bernard‐Tessier,Anna Patrikidou,Emeline Colomba,Ronan Flippot,Alina Fuerea,Nathalie Auger,Maud Ngo Camus,Benjamin Besse,Ludovic Lacroix,Étienne Rouleau,Santiago Ponce,Antoîne Italiano,Natacha Naoun
出处
期刊:European Journal of Cancer [Elsevier BV]
卷期号:195: 113368-113368 被引量:4
标识
DOI:10.1016/j.ejca.2023.113368
摘要

Background Genomic stratification may help improve the management of patients with metastatic urothelial cancer (mUC), given the recent identification of targetable alterations. However, the collection of tissue samples remains challenging. Here, we assessed the clinical utility of plasma circulating tumour DNA (ctDNA) sequencing in these patients. Methods Patients with mUC were prospectively enroled in the STING trial (NCT04932525), in which ctDNA was profiled using the Foundation One Liquid CDx Assay (324 genes, blood tumour mutational burden [bTMB], microsatellite instability status). Each genomic report was reviewed by a multidisciplinary tumor board (MTB). Results Between January 2021 and June 2022, 140 mUC patients underwent molecular profiling. The median time to obtain the assay results was 20 days ((confidence interval) CI95%: [20,21]). The ctDNA analysis reproduced the somatic genomic landscape of previous tissue-based cohorts. Concordance for serial ctDNA samples was strong (r = 0.843 CI95%: [0.631–0.938], p < 0.001). At least one actionable target was detected in 63 patients (45%) with a total of 35 actionable alterations, including bTMB high (≥10 mutations/Mb) (N = 39, 21.1%), FGFR3 (N = 20, 10.8%), and Homologous recombination deficiency (HRD) alterations (N = 14, 7.6%). MTB recommended matched therapy in 63 patients (45.0%). Eight patients (5.7%) were treated, with an overall response rate of 50% (CI95%: 15.70–84.30) and a median progression-free survival (PFS) of 5.2 months (CI95%: 4.1 - NR). FGFR3 alterations were associated with a shorter PFS in patients treated with immunotherapy. Conclusion Overall, we demonstrated that genomic profiling with ctDNAs in mUC is a reliable and feasible approach for the timely initiation of genotype-matched therapies.
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