Crabb, SJ;
Hussain, S;
Soulis, E;
Hinsley, S;
Dempsey, L;
Trevethan, A;
Song, Y;
... Jones, RJ; + view all
(2023)
A Randomized, Double-Blind, Biomarker-Selected, Phase II Clinical Trial of Maintenance Poly ADP-Ribose Polymerase Inhibition with Rucaparib Following Chemotherapy for Metastatic Urothelial Carcinoma.
Journal of Clinical Oncology
, 41
(1)
pp. 54-64.
10.1200/JCO.22.00405.
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Abstract
PURPOSE A DNA repair deficiency (DRD) phenotype exists within a subset of metastatic urothelial carcinomas (mUC) predicting benefit from platinum-based chemotherapy. We tested switch maintenance therapy with the poly ADP-ribose polymerase inhibitor rucaparib, following chemotherapy, for DRD biomarker-positive mUC.METHODSDRD biomarker-positive mUC patients, within 10 weeks of chemotherapy, and without cancer progression, were randomly assigned (1:1) to maintenance rucaparib 600 mg twice a day orally, or placebo, until disease progression. The primary end point was progression-free survival (PFS). Statistical analysis targeted a hazard ratio of 0.5 with a 20% one-sided α for this signal-seeking trial. PFS (RECIST 1.1) was compared between trial arms, by intention to treat, within a Cox model.RESULTSOut of 248 patients, 74 (29.8%) were DRD biomarker-positive and 40 were randomly assigned. A total of 12 (60%) and 20 (100%) PFS events occurred in the rucaparib and placebo arms, respectively (median follow-up was 94.6 weeks in those still alive). Median PFS was 35.3 weeks (80% CI, 11.7 to 35.6) with rucaparib and 15.1 weeks (80% CI, 11.9 to 22.6) with placebo (hazard ratio, 0.53; 80% CI, 0.30 to 0.92; one-sided P =.07). In the safety population (n = 39) treatment-related adverse events were mostly low grade. Patients received a median duration of 10 rucaparib or six placebo cycles on treatment. Treatment-related adverse events (all grades) of fatigue (63.2% v 30.0%), nausea (36.8% v 5.0%), rash (21.1% v 0%), and raised alanine aminotransferase (57.9% v 10%) were more common with rucaparib.CONCLUSIONMaintenance rucaparib, following platinum-based chemotherapy, extended PFS in DRD biomarker-selected patients with mUC and was tolerable. Further investigation of poly ADP-ribose polymerase inhibition in selected patients with mUC is warranted.
| Type: | Article |
|---|---|
| Title: | A Randomized, Double-Blind, Biomarker-Selected, Phase II Clinical Trial of Maintenance Poly ADP-Ribose Polymerase Inhibition with Rucaparib Following Chemotherapy for Metastatic Urothelial Carcinoma |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1200/JCO.22.00405 |
| Publisher version: | https://doi.org/10.1200/JCO.22.00405 |
| Language: | English |
| Additional information: | © The Authors 2023. Original content in this paper is licensed under the terms of the Creative Commons Attribution 4.0 International (CC BY 4.0) Licence (https://creativecommons.org/licenses/by/4.0/). |
| Keywords: | Female, Humans, Ovarian Neoplasms, Poly(ADP-ribose) Polymerases, Carcinoma, Transitional Cell, Urinary Bladder Neoplasms, Platinum, Biomarkers, Adenosine Diphosphate Ribose, Double-Blind Method, Antineoplastic Combined Chemotherapy Protocols, Maintenance Chemotherapy |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10170742 |
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