A Phase II Trial of Prexasertib (LY2606368) in Patients With Extensive-Stage Small-Cell Lung Cancer

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dc.authoridZhang, Jialiang/0000-0003-1626-6674
dc.authoridBondarenko, Igor/0000-0002-7071-2471
dc.authoridForster, Martin/0000-0003-3876-7269
dc.authoridNAVARRO, ALEJANDRO/0000-0001-5903-270X
dc.authorwosidZavizion, Viktor/C-2550-2019
dc.authorwosidZhang, Jialiang/HGU-6164-2022
dc.authorwosidBondarenko, Igor/U-5156-2017
dc.contributor.authorByers, Lauren Averett
dc.contributor.authorNavarro, Alejandro
dc.contributor.authorSchaefer, Eric
dc.contributor.authorJohnson, Melissa
dc.contributor.authorOzguroglu, Mustafa
dc.contributor.authorHan, Ji-Youn
dc.contributor.authorBondarenko, Igor
dc.date.accessioned2024-06-12T10:56:13Z
dc.date.available2024-06-12T10:56:13Z
dc.date.issued2021
dc.departmentTrakya Üniversitesien_US
dc.description.abstractPatients with extensive-stage small-cell lung cancer (ED-SCLC) need improved outcomes in the relapsed/refractory setting. This phase II study evaluated the safety and efficacy of prexasertib, a checkpoint kinase 1 inhibitor, in platinum-sensitive and platinum-refractory ED-SCLC. Prexasertib demonstrated response rates of 5.2% in platinum-sensitive and 0% in platinum-refractory ED-SCLC. Prexasertib did not show prespecified efficacy as monotherapy in ED-SCLC. Background: This study assessed the checkpoint kinase 1 inhibitor prexasertib in patients with extensive-stage small cell lung cancer (ED-SCLC). Patients and Methods: This was a parallel-cohort phase II study of 105 mg/m(2) prexasertib once every 14 days for patients who progressed after no more than two prior therapies and had platinum-sensitive (Cohort 1) or platinum-resistant/platinum-refractory (Cohort 2) disease. The primary endpoint was objective response rate (ORR). Secondary endpoints included disease control rate (DCR), progression-free survival (PFS), overall survival (OS), safety, and pharmacokinetics. Exploratory endpoints included biomarker identification and assessment of an alternative regimen (Cohort 3: 40 mg/m(2) days 1-3, 14-day cycle). Results: In Cohort 1 ( n = 58), ORR was 5.2%; DCR, 31%; median PFS, 1.41 months (95% confidence interval [CI], 1.31-1.64); and median OS, 5.42 months (95% CI, 3.75-8.51). In Cohort 2 ( n = 60), ORR was 0%; DCR, 20%; median PFS, 1.36 months (95% CI, 1.25-1.45); and median OS, 3.15 months (95% CI, 2.27-5.52). The most frequent all-grade, related, treatment-emergent adverse events were decreased neutrophil count (Cohort 1, 69.6%; Cohort 2, 73.3%), decreased platelet count (Cohort 1, 51.8%; Cohort 2, 50.0%), decreased white blood cell count (Cohort 1, 28.6%; Cohort 2, 40.0%), and anemia (Cohort 1, 39.3%; Cohort 2, 28.3%). Eleven patients (19.6%) in Cohort 1 and one patient (1.7%) in Cohort 2 experienced grade >= 3 febrile neutropenia. Prexasertib pharmacokinetics were consistent with prior studies. Cohort 3 outcomes were similar to those of Cohorts 1 and 2. No actionable biomarkers were identified. Conclusion: Prexasertib did not demonstrate activity to warrant future development as monotherapy in ED-SCLC. (C) 2021 The Authors. Published by Elsevier Inc.en_US
dc.description.sponsorshipUniversity College London/University College London Hospitals NHS Foundation Trust (UCLH) National Institute for Health Research (NIHR) Biomedical Research Centre; University College London Experimental Cancer Medicine Centre; Eli Lilly and Companyen_US
dc.description.sponsorshipWe thank the patients who participated in this trial and the study coordinators, nurses, nurse practitioners, clinical research assistants, and doctors who assisted with the research. The authors also thank Erin Wagner from BioStat Solutions, Inc., for statistical support and Lisa Golden, Rod Decker, and Elizabeth Spoljoric for their input and contributions to the study. MDF is supported by the University College London/University College London Hospitals NHS Foundation Trust (UCLH) National Institute for Health Research (NIHR) Biomedical Research Centre and runs early phase studies in the NIHR UCLH Clinical Research Facility supported by the University College London Experimental Cancer Medicine Centre. Eli Lilly and Company contracted with Syneos Health for writing support provided by Andrea D. Humphries, PhD, and editing support provided by Noelle Gasco.; This research was funded by Eli Lilly and Company. Eli Lilly and Company provides access to all individual participant data collected during the trial, after anonymization, with the exception of pharmacokinetic or genetic data. Data are available to request 6 months after the indication studied has been approved in the United States and European Union and after primary publication acceptance, whichever is later. No expiration date of data requests is currently set once data are made available. Access is provided after a proposal has been approved by an independent review committee identified for this purpose and after receipt of a signed data sharing agreement. Data and documents, including the study protocol, statistical analysis plan, clinical study report, and blank or annotated case report forms, will be provided in a secure data sharing environment. For details on submitting a request, see the instructions provided at www.vivli.org.en_US
dc.identifier.doi10.1016/j.cllc.2021.04.005
dc.identifier.endpage540en_US
dc.identifier.issn1525-7304
dc.identifier.issn1938-0690
dc.identifier.issue6en_US
dc.identifier.pmid34034991en_US
dc.identifier.scopus2-s2.0-85106618250en_US
dc.identifier.scopusqualityQ1en_US
dc.identifier.startpage531en_US
dc.identifier.urihttps://doi.org/10.1016/j.cllc.2021.04.005
dc.identifier.urihttps://hdl.handle.net/20.500.14551/19695
dc.identifier.volume22en_US
dc.identifier.wosWOS:000723160600005en_US
dc.identifier.wosqualityQ2en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherCig Media Group, Lpen_US
dc.relation.ispartofClinical Lung Canceren_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectCheckpoint Kinase 1 Inhibitoren_US
dc.subjectRelapseden_US
dc.subjectRefractoryen_US
dc.subjectSmall Cell Lung Canceren_US
dc.subjectPharmacokineticsen_US
dc.subjectBiomarkeren_US
dc.subject2nd-Line Treatmenten_US
dc.subjectTopotecanen_US
dc.subjectCyclophosphamideen_US
dc.subjectVincristineen_US
dc.subjectCisplatinen_US
dc.titleA Phase II Trial of Prexasertib (LY2606368) in Patients With Extensive-Stage Small-Cell Lung Canceren_US
dc.typeArticleen_US

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