Sistema de Salut de Catalunya
Institut Català de la Salut
[Grivas P] Department of Medicine, Division of Medical Oncology, University of Washington, Seattle, WA 98109, USA. Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA. Seattle Cancer Care Alliance, Seattle, WA 98109, USA. [Loriot Y] Department of Medicine, Gustave Roussy Cancer Campus, INSERM U981, Université Paris-Saclay, 94800 Villejuif, France. [Morales-Barrera R] Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Teo MY] Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. [Zakharia Y] Division of Hematology, Oncology, and Blood and Marrow Transplant, University of Iowa and Holden Comprehensive Cancer Center, Iowa City, IA 52242, USA. [Feyerabend S] Studienpraxis Urologie, 72622 Nürtingen, Germany
Vall d'Hebron Barcelona Hospital Campus
2022-02-22T07:53:40Z
2022-02-22T07:53:40Z
2021-05-24
Càncer de bufeta; Rucaparib; Carcinoma urotelial
Cáncer de vejiga; Rucaparib; Carcinoma urotelial
Bladder cancer; Rucaparib; Urothelial carcinoma
Background ATLAS evaluated the efficacy and safety of the PARP inhibitor rucaparib in patients with previously treated locally advanced/unresectable or metastatic urothelial carcinoma (UC). Methods Patients with UC were enrolled independent of tumor homologous recombination deficiency (HRD) status and received rucaparib 600 mg BID. The primary endpoint was investigator-assessed objective response rate (RECIST v1.1) in the intent-to-treat and HRD-positive (loss of genome-wide heterozygosity ≥10%) populations. Key secondary endpoints were progression-free survival (PFS) and safety. Disease control rate (DCR) was defined post-hoc as the proportion of patients with a confirmed complete or partial response (PR), or stable disease lasting ≥16 weeks. Results Of 97 enrolled patients, 20 (20.6%) were HRD-positive, 30 (30.9%) HRD-negative, and 47 (48.5%) HRD-indeterminate. Among 95 evaluable patients, there were no confirmed responses. However, reductions in the sum of target lesions were observed, including 6 (6.3%) patients with unconfirmed PR. DCR was 11.6%; median PFS was 1.8 months (95% CI, 1.6–1.9). No relationship was observed between HRD status and efficacy endpoints. Median treatment duration was 1.8 months (range, 0.1–10.1). Most frequent any-grade treatment-emergent adverse events were asthenia/fatigue (57.7%), nausea (42.3%), and anemia (36.1%). Of 64 patients with data from tumor tissue samples, 10 (15.6%) had a deleterious alteration in a DNA damage repair pathway gene, including four with a deleterious BRCA1 or BRCA2 alteration. Conclusions Rucaparib did not show significant activity in unselected patients with advanced UC regardless of HRD status. The safety profile was consistent with that observed in patients with ovarian or prostate cancer.
The work was supported by Clovis Oncology (no grant number) and was designed by the sponsor, P. Grivas, and S. Chowdhury.
Article
Published version
English
Bufeta - Càncer - Tractament; Inhibidors enzimàtics - Ús terapèutic - Eficàcia; DISEASES::Neoplasms::Neoplasms by Site::Urogenital Neoplasms::Urologic Neoplasms::Urinary Bladder Neoplasms; Other subheadings::Other subheadings::Other subheadings::/drug therapy; CHEMICALS AND DRUGS::Chemical Actions and Uses::Pharmacologic Actions::Molecular Mechanisms of Pharmacological Action::Enzyme Inhibitors::Poly(ADP-ribose) Polymerase Inhibitors; Other subheadings::Other subheadings::Other subheadings::/administration & dosage; ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias urogenitales::neoplasias urológicas::neoplasias de la vejiga; Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia; COMPUESTOS QUÍMICOS Y DROGAS::acciones y usos químicos::acciones farmacológicas::mecanismos moleculares de acción farmacológica::inhibidores enzimáticos::inhibidores de poli(ADP-ribosa) polimerasas; Otros calificadores::Otros calificadores::Otros calificadores::/administración & dosificación
BMC
BMC Cancer;21
https://doi.org/10.1186/s12885-021-08085-z
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
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