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SHR Neuro Krebs Kardio Lipid Stoffw Microb

Riedl, JM; Hasenleithner, SO; Pregartner, G; Scheipner, L; Posch, F; Groller, K; Kashofer, K; Jahn, SW; Bauernhofer, T; Pichler, M; Stöger, H; Berghold, A; Hoefler, G; Speicher, MR; Heitzer, E; Gerger, A.
Profiling of circulating tumor DNA and tumor tissue for treatment selection in patients with advanced and refractory carcinoma: a prospective, two-stage phase II Individualized Cancer Treatment trial.
Ther Adv Med Oncol. 2021; 13:1758835920987658 Doi: 10.1177/1758835920987658 [OPEN ACCESS]
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Führende Autor*innen der Med Uni Graz

Gerger Armin

Hasenleithner Samantha

Heitzer Ellen

Riedl Jakob

Co-Autor*innen der Med Uni Graz

Bauernhofer Thomas

Berghold Andrea

Groller Karin

Höfler Gerald

Jahn Stephan

Kashofer Karl

Pichler Martin

Posch Florian

Pregartner Gudrun

Scheipner Lukas

Speicher Michael

Stöger Herbert

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Abstract:

Background: Molecular profiling (MP) represents an opportunity to match patients to a targeted therapy and when tumor tissue is unavailable, circulating tumor deoxyribonucleic acid (ctDNA) can be harnessed as a non-invasive analyte for this purpose. We evaluated the success of a targeted therapy selected by profiling of ctDNA and tissue in patients with advanced and refractory carcinoma. Patients and methods: A blood draw as well as an optional tissue biopsy were obtained for MP. Whole-genome sequencing and a cancer hotspot panel were performed, and publicly available databases were used to match the molecular profile to targeted treatments. The primary endpoint was the progression-free survival (PFS) ratio (PFS on MP-guided therapy/PFS on the last evidence-based therapy), whereas the success of the targeted therapy was defined as a PFS ratio ⩾1.2. To test the impact of molecular profile-treatment matching strategies, we retrospectively analyzed selected cases via the CureMatch PreciGENE™ decision support algorithm. Results: Interim analysis of 24 patients yielded informative results from 20 patients (83%). A potential tumor-specific drug could be matched in 11 patients (46%) and eight (33%) received a matched treatment. Median PFS in the matched treatment group was 61.5 days [interquartile range (IQR) 49.8-71.0] compared with 81.5 days (IQR 68.5-117.8) for the last evidence-based treatment, resulting in a median PFS ratio of 0.7 (IQR 0.6-0.9). Hence, as no patient experienced a PFS ratio ⩾1.2, the study was terminated. Except for one case, the CureMatch analysis identified either a two-drug or three-drug combination option. Conclusions: Our study employed a histotype-agnostic approach to harness molecular profiling data from both ctDNA and metastatic tumor tissue. The outcome results indicate that more innovative approaches to study design and matching algorithms are necessary to achieve improved patient outcomes.EU Clinical Trials Registry (https://www.clinicaltrialsregister.eu): EudraCT: 2014-005341-44.

Find related publications in this database (Keywords)

circulating tumor DNA

molecular profiling

progression-free survival ratio

refractory cancer

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