The pediatric precision oncology study INFORM: Clinical outcome and benefit for molecular subgroups.

Medientyp: E-Artikel

Titel: The pediatric precision oncology study INFORM: Clinical outcome and benefit for molecular subgroups

Beteiligte: van Tilburg, Cornelis Martinus; Pfaff, Elke; Pajtler, Kristian W.; Langenberg, Karin P.S.; Fiesel, Petra; Jones, Barbara C.; Balasubramanian, Gnana Prakash; Stark, Sebastian; Johann, Pascal D.; Blattner-Johnson, Mirjam; Schramm, Kathrin; Jäger, Natalie; von Deimling, Andreas; Dirksen, Uta; Freitag, Angelika; Witt, Ruth; Lichter, Peter; Jones, David T.W.; Pfister, Stefan M.; Witt, Olaf

Erschienen: American Society of Clinical Oncology (ASCO), 2020

Sprache: Englisch

DOI: 10.1200/jco.2020.38.18_suppl.lba10503

ISSN: 0732-183X; 1527-7755

Schlagwörter: Cancer Research ; Oncology

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Beschreibung: LBA10503 Background: Several pediatric precision oncology programs have identified molecular actionable variants. However, the clinical benefit is largely unknown. We here report a target prioritization algorithm and associated clinical outcome. Methods: INFORM is a prospective, non-interventional, multi-center, multi-national, and feasibility registry collecting clinical and molecular data. Patients with refractory/relapsed/progressive malignant disease, including primary diagnosis high-risk entities, can be enrolled. Fresh frozen tumor material (incl. germline DNA) was subjected to WES, lcWGS, RNA-Seq, RNA expression array and DNA-methylation. A weekly interdisciplinary molecular board reviewed and prioritized alterations based on a 7- step scale from ‘very high’ to ‘very low’, depending on the type of alteration and its entity specific relevance (described by Worst et al. Eur J Cancer 2016). Results: To date, more than 1300 patients were enrolled. 525 patients finished follow-up and were included in this analysis. They were enrolled in 72 centers in 8 countries. The median age was 12.0 (range 0 - 40) years. Average turnaround time from submission to report was 25.4 days. Median PFS and OS were 116 (95% CI 105 – 135) and 289 (95% CI 250 – 335) days. The distribution of the highest priority target per patient was: very high 8.0%, high 14.8%, moderate 20.3%, intermediate 23.6%, borderline 14.4%, low 2.5%, very low 1.0% and no actionable target 15.4%. 149 patients received targeted treatment on the basis of identified targets, of which 20 had a very high priority target (mostly ALK, BRAF and NRAS mutations and MET and NTRK-fusions) with a median PFS of 204.5 (95% CI 91.0 – 628.0) compared to 114 (95% CI 103 – 133) days in all other 505 patients (p = 0.0095). OS did not show clinically relevant differences. Explorative analysis of the time to progression (TTP) ratio (before compared to after enrollment) showed that patients treated according to a very high priority target had a higher TTP ratio (1.0) compared to all other patients (0.7). Possible predisposition syndromes were identified in 7.8% of patients, half of which were newly diagnosed. Methylation analysis provided a diagnosis refinement in 8% of CNS tumors. Conclusions: Pediatric precision oncology in a real world, multi-national setting is feasible. The prioritization algorithm identifies subgroups benefitting from molecularly matched targeted treatment. Still, for the patients without a very high priority target further layers of molecular and functional data should be incorporated in future programs.

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