Biomarker-selected phase 2 trial of maintenance rucaparib after chemotherapy for metastatic urothelial carcinoma

A DNA repair deficiency (DRD) phenotype exists within a subset of metastatic urothelial carcinomas (mUC) predicting benefit from platinum-based chemotherapy. A multicenter randomized phase 2 study in the United Kingdom evaluated switch maintenance therapy with the PARP inhibitor rucaparib, following chemotherapy, for DRD biomarker-positive mUC. The study included 40 patients who were without cancer progression within ten weeks of chemotherapy. Patients were randomized to rucaparib (orally 600 mg twice daily) or placebo maintenance. The median progression-free survival was 35.3 weeks with rucaparib versus 15.1 weeks with placebo (HR 0.53; 80% CI 0.30-0.92). Treatment-related adverse events were mostly low grade. The authors conclude that maintenance rucaparib after platinum-based chemotherapy extended PFS in DRD biomarker-selected mUC patients and was tolerable.