ATLANTIS Rucaparib Trial Shows Extended Progression Free Survival in DNA Repair Deficiency Biomarker Selected Patients With Metastatic Urothelial Carcinoma

Biomarker positive patients were randomized to maintenance rucaparib 600 mg or matched placebo within 10 weeks of completing PBC until disease progression.

A randomized, double-blind phase 2 clinical trial of maintenance PARP inhibition following chemotherapy for metastatic urothelial carcinoma (mUC) demonstrated that the treatment extended progression free survival (PFS) in DNA repair deficiency (DRD) biomarker selected patients with mUC and was reported to be tolerable by the patients included in the study, according to researchers in a session at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting.

The researchers hypothesized that switching the maintenance therapy with the PARP inhibitor rucaparib (Rubraca; Clovis Oncology) in patients who have derived clinical benefit from platinum-based chemotherapy (PBC) would improve outcomes for patients with mUC hiding a DRD biomarker.

During the ATLANTIS study, researchers tested multiple biomarker selected maintenance therapies for mUC after 4 to 8 PBC cycles without disease progression. Biomarker positive patients were randomized to maintenance rucaparib 600 mg or matched placebo within 10 weeks of completing PBC until disease progression.

Out of the 279 screened patients, 26.5% were biomarker positive. The median PFS was 35.3 weeks with rucaparib and 15.1 weeks with placebo. In the safety population, treatment related adverse events (AEs) were mostly low grade, and rucaparib was tolerable with a median duration of 10 rucaparib or 6 placebo cycles on treatment. The most frequent treatment related AEs with rucaparib were fatigue, nausea, and rash.

REFERENCE

Crabb SJ, Hussain SA, Soulis E, et al. A randomized, double blind, biomarker selected, phase II clinical trial of maintenance PARP inhibition following chemotherapy for metastatic urothelial carcinoma (mUC): Final analysis of the ATLANTIS rucaparib arm. 2022 ASCO Annual Meeting. Accessed June 6, 2022. 10.1200/JCO.2022.40.6_suppl.436