Abstract
Rucaparib for recurrent, locally advanced, or metastatic urothelial carcinoma (mUC): Results from ATLAS, a phase II open-label trial
Journal of clinical oncology, Vol.38(6_suppl), pp.440-440
02/20/2020
DOI: 10.1200/JCO.2020.38.6_suppl.440
Abstract
Abstract only
440
Background: ATLAS (NCT03397394) evaluated the efficacy/safety of the PARP inhibitor (PARPi) rucaparib in patients (pts) with previously treated locally advanced/unresectable UC or mUC. Methods: Pts with measurable disease who had progressed after 1–2 prior regimens (ie, platinum-based chemotherapy [PBC] and/or immune checkpoint inhibitors [ICI]) were enrolled regardless of tumor homologous recombination deficiency (HRD) status. Prior PARPi was not allowed. Pts received rucaparib 600 mg PO BID. Baseline tumor tissue or archival tissue ≤6 mo without intervening therapy was required; serial circulating tumor DNA samples were collected. Primary endpoint was investigator-assessed objective response rate (RECIST v1.1) in the intent-to-treat and HRD-positive (defined as genomic loss of heterozygosity ≥10%) populations. Key secondary endpoints: progression-free survival (PFS) and safety. Clinical benefit rate (CBR) was defined as complete or partial response or stable disease (SD) lasting ≥16 weeks. Results: As of Oct 7, 2019, 97 pts were enrolled (median age 66 y [range, 39–87]); most were men (n=76, 78.4%) and had ECOG PS 1 (n=65, 67.0%). Sixty-six pts (68.0%) had both prior PBC and ICI. Twenty pts (20.6%) were HRD-positive, 30 (30.9%) were HRD-negative and 47 (48.5%) had unknown HRD status; 4 pts had a deleterious BRCA1/2 alteration. Median time on treatment was 54 d (range, 2–224). There were no confirmed responses. Of 96 evaluable pts, 27 (28.1%) had a best response of SD; CBR was 12.5% and median PFS was 1.8 mo. No relationship was observed between HRD status and clinical activity. Treatment was discontinued by 93 pts (95.9%), mainly due to radiologic or clinical progression (73.1%). Most frequent any grade treatment-emergent (any cause) adverse events were asthenia/fatigue (n=56, 57.7%), nausea (n=40, 41.2%), and anemia (n=34, 35.1%). Conclusions: Single agent rucaparib did not show activity in pts with previously treated advanced UC and enrollment was suspended at the first interim analysis. The safety profile was consistent with that observed in pts with ovarian cancer. Next generation sequencing–based characterization of the genomic landscape of mUC will be presented. Clinical trial information: NCT03397394.
Details
- Title: Subtitle
- Rucaparib for recurrent, locally advanced, or metastatic urothelial carcinoma (mUC): Results from ATLAS, a phase II open-label trial
- Creators
- Petros Grivas - Seattle Cancer Care AllianceYohann Loriot - Institut Gustave RoussySusan Feyerabend - Studienpraxis Urologie, Nürtingen, GermanyRafael Morales-Barrera - Universitat Autònoma de BarcelonaMin Yuen Teo - Memorial Sloan Kettering Cancer CenterNicholas J. Vogelzang - Comprehensive Cancer Centers of NevadaEnrique Grande - MD Anderson Cancer Center MadridYousef Zakharia - University of IowaNabil Adra - Indiana University HealthAjjai Shivaram Alva - University of Michigan–Ann ArborAndrea Necchi - Fondazione IRCCS Istituto Nazionale dei TumoriSumati Gupta - Huntsman Cancer InstituteDebra Hannah Josephs - Guy's and St Thomas' NHS Foundation TrustAlejo Rodriguez-Vida - Hospital Del MarSandy Srinivas - Stanford UniversityKenton Wride - Clovis OncologyDaleen Thomas - Clovis OncologyRachel Dusek - Clovis OncologyDale L. Nepert - Clovis OncologySimon Chowdhury - Guy's and St Thomas' NHS Foundation Trust
- Resource Type
- Abstract
- Publication Details
- Journal of clinical oncology, Vol.38(6_suppl), pp.440-440
- DOI
- 10.1200/JCO.2020.38.6_suppl.440
- ISSN
- 0732-183X
- eISSN
- 1527-7755
- Grant note
- name: Clovis Oncology, Inc.
- Language
- English
- Date published
- 02/20/2020
- Academic Unit
- Internal Medicine; Hematology, Oncology, and Blood & Marrow Transplantation
- Record Identifier
- 9984548380002771
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