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Efficacy and safety of rucaparib in previously treated, locally advanced or metastatic urothelial carcinoma from a phase 2, open-label trial (ATLAS)
- Source :
- BMC Cancer, BMC Cancer, BioMed Central, 2021, 21 (1), pp.593. ⟨10.1186/s12885-021-08085-z⟩, BMC Cancer, 2021, 21 (1), pp.593. ⟨10.1186/s12885-021-08085-z⟩, BMC Cancer, Vol 21, Iss 1, Pp 1-13 (2021), Scientia
- Publication Year :
- 2021
- Publisher :
- Springer Science and Business Media LLC, 2021.
-
Abstract
- BackgroundATLAS evaluated the efficacy and safety of the PARP inhibitor rucaparib in patients with previously treated locally advanced/unresectable or metastatic urothelial carcinoma (UC).MethodsPatients 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.ResultsOf 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 deleteriousBRCA1orBRCA2alteration.ConclusionsRucaparib 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.Trial registrationThis trial was registered inClinicalTrials.gov(NCT03397394). Date of registration: 12 January 2018. This trial was registered in EudraCT (2017–004166-10).
- Subjects :
- Male
0301 basic medicine
Oncology
Cancer Research
Indoles
DNA Repair
[SDV]Life Sciences [q-bio]
Administration, Oral
Loss of Heterozygosity
Other subheadings::Other subheadings::/drug therapy [Other subheadings]
Prostate cancer
chemistry.chemical_compound
0302 clinical medicine
Clinical endpoint
Inhibidors enzimàtics - Ús terapèutic - Eficàcia
RC254-282
BRCA1 Protein
Bladder cancer
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Middle Aged
Progression-Free Survival
3. Good health
[SDV] Life Sciences [q-bio]
030220 oncology & carcinogenesis
Bufeta - Càncer - Tractament
Other subheadings::Other subheadings::/administration & dosage [Other subheadings]
Female
Urothelial carcinoma
medicine.symptom
Research Article
medicine.medical_specialty
Metastatic Urothelial Carcinoma
Anemia
Nausea
Urinary Bladder
Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores]
Poly(ADP-ribose) Polymerase Inhibitors
03 medical and health sciences
Internal medicine
Genetics
medicine
Humans
Chemical Actions and Uses::Pharmacologic Actions::Molecular Mechanisms of Pharmacological Action::Enzyme Inhibitors::Poly(ADP-ribose) Polymerase Inhibitors [CHEMICALS AND DRUGS]
Adverse effect
Rucaparib
Neoplasms::Neoplasms by Site::Urogenital Neoplasms::Urologic Neoplasms::Urinary Bladder Neoplasms [DISEASES]
Response Evaluation Criteria in Solid Tumors
Aged
BRCA2 Protein
Genomic biomarkers
Carcinoma, Transitional Cell
Otros calificadores::Otros calificadores::/administración & dosificación [Otros calificadores]
neoplasias::neoplasias por localización::neoplasias urogenitales::neoplasias urológicas::neoplasias de la vejiga [ENFERMEDADES]
business.industry
acciones y usos químicos::acciones farmacológicas::mecanismos moleculares de acción farmacológica::inhibidores enzimáticos::inhibidores de poli(ADP-ribosa) polimerasas [COMPUESTOS QUÍMICOS Y DROGAS]
medicine.disease
PARP inhibitor
030104 developmental biology
Urinary Bladder Neoplasms
chemistry
business
Follow-Up Studies
Subjects
Details
- ISSN :
- 14712407 and 03397394
- Volume :
- 21
- Database :
- OpenAIRE
- Journal :
- BMC Cancer
- Accession number :
- edsair.doi.dedup.....3fd23d13c81759eb9e25d93f435c085c