Efficacy of Trabectedin and Olaparib in homologous repair deficient neuroendocrine neoplasms – A subgroup analysis of the TOP-ART / PMO-1603 trial

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Introduction: Genomic alterations resulting in homologous recombination deficiency (HRD) occur in a variety of cancers including neuroendocrine neoplasms (NEN). HRD-positive tumours are sensitive to PARP inhibitors such as olaparib. The DNA minor groove binder trabectedin leads to DNA double strand breaks and PARP activation. The combination of Trabectedin + Olaparib (TrO) may therefore have synergistic effects in HRD-positive tumours.

Aim(s): The TOP-ART / PMO-1603 trial evaluated the efficacy of TrO in HRD-positive solid tumours, preliminary results were presented at ESMO 2024. This subgroup analysis highlights the efficacy of TrO in NEN.

Materials and methods: TOP-ART was a prospective randomised phase II trial comparing TrO with a treatment of physician's choice (PC). HRD positivity was determined by whole exome/genome sequencing with a newly developed score. Patients were randomised 1:1 to TrO vs. PC and treated until disease progression (PD). Cross-over upon PD was allowed. The primary endpoint was disease control rate (DCR) at 16 weeks.

Conference:

Presenting Author: Apostolidis L

Authors: Apostolidis L, Ruebsam M, Teleanu M, Wagner S, Dorman K,

Keywords: Neuroendocrine Tumour, Neuroendocrine Carcinoma, targeted therapy, chemotherapy, HRD, olaparib, trabectedin, net, nec,