Evidence map›Paper›PMID 29361470›Full record

ArticleThe Lancet. Oncology2018

Prexasertib, a cell cycle checkpoint kinase 1 and 2 inhibitor, in BRCA wild-type recurrent high-grade serous ovarian cancer: a first-in-class proof-of-concept phase 2 study.

Jung-Min Lee, Jayakumar Nair, Alexandra Zimmer, Stanley Lipkowitz, Christina M Annunziata, Maria J Merino, Elizabeth M Swisher, Maria I Harrell, Jane B Trepel, Min-Jung Lee and 6 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Lancet. Oncology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 141 papers.

0numbers the graph read from it
0cells of the map it votes in
141citing papers in PubMed
9.7field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

141 citing papers in PubMed, 210 citations in OpenAlex.

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  3. Science translational medicine · 2023
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  6. Clinical outcomes of prexasertib monotherapy in recurrentJournal for immunotherapy of cancer · 2020
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81 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

16 authors at 2 institutions in 1 country.

Jung-Min LeeWomen's Malignancies Branch, National Cancer Institute, Bethesda, MD, USA. Electronic address: leej6@mail.nih.gov.
Jayakumar NairWomen's Malignancies Branch, National Cancer Institute, Bethesda, MD, USA.
Alexandra ZimmerWomen's Malignancies Branch, National Cancer Institute, Bethesda, MD, USA.
Stanley LipkowitzWomen's Malignancies Branch, National Cancer Institute, Bethesda, MD, USA.
Christina M AnnunziataWomen's Malignancies Branch, National Cancer Institute, Bethesda, MD, USA.
Maria J MerinoLaboratory of Pathology, National Cancer Institute, Bethesda, MD, USA.
Elizabeth M SwisherDivision of Gynecologic Oncology, Departments of Obstetrics and Gynecology, University of Washington, Seattle, WA, USA.
Maria I HarrellDivision of Gynecologic Oncology, Departments of Obstetrics and Gynecology, University of Washington, Seattle, WA, USA.
Jane B TrepelDevelopmental Therapeutics Branch, National Cancer Institute, Bethesda, MD, USA.
Min-Jung LeeDevelopmental Therapeutics Branch, National Cancer Institute, Bethesda, MD, USA.
Mohammad H BagheriDepartment of Radiology and Imaging Sciences, National Cancer Institute, Bethesda, MD, USA.
Dana-Adriana BotesteanuWomen's Malignancies Branch, National Cancer Institute, Bethesda, MD, USA.
Seth M SteinbergBiostatistics and Data Management Section, National Cancer Institute, Bethesda, MD, USA.
Lori MinasianWomen's Malignancies Branch, National Cancer Institute, Bethesda, MD, USA.
Irene EkwedeWomen's Malignancies Branch, National Cancer Institute, Bethesda, MD, USA.
Elise C KohnWomen's Malignancies Branch, National Cancer Institute, Bethesda, MD, USA.
National Cancer Institute · USUniversity of Washington · US

Funding

Targeting DNA damage repair and related pathways in HRD-womens cancersZIABC011525 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI LEE, JUNG-MIN · 2013 to 2025
$14.8M
Signal Transduction Events and the Regulation of Cell GrowthZICSC006743 · NCI · DIVISION OF CLINICAL SCIENCES - NCI · PI TREPEL, JANE B · 2009 to 2023
$13.8M
Intramural NIH HHS ZIA BC011525NCI NIH HHS ZIA BC011525
6 · The paper itself

Abstract

backgroundHigh-grade serous ovarian carcinoma is characterised by TP53 mutations, DNA repair defects, and genomic instability. We hypothesised that prexasertib (LY2606368), a cell cycle checkpoint kinase 1 and 2 inhibitor, would be active in BRCA wild-type disease.

methodsIn an open-label, single-centre, two-stage, proof-of-concept phase 2 study, we enrolled women aged 18 years or older with measurable, recurrent high-grade serous or high-grade endometrioid ovarian carcinoma. All patients had a negative family history of hereditary breast and ovarian cancer or known BRCA wild-type status, measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, Eastern Cooperative Oncology Group performance status score 0-2, and adequate haematological, renal, hepatic, and bone-marrow function. Patients received intravenous prexasertib 105 mg/m

findingsBetween Jan 20, 2015, and Nov 2, 2016, we enrolled 28 women with a median age of 64 years (IQR 58·0-69·5) who had previously received a median of 5·0 (IQR 2·5-5·0) systemic therapies. Most patients (22 [79%]) had platinum-resistant or platinum-refractory disease. All women received at least one dose of prexasertib, but four (14%) of 28 patients were not assessable for RECIST response. Eight (33%, 95% CI 16-55) of 24 patients assessable per protocol had partial responses. In the intention-to-treat population, eight (29%, 95% CI 13-49) of 28 had a partial responses. The most common (in >10% patients) grade 3 or 4 treatment-emergent adverse events were neutropenia in 26 (93%) of 28 patients, reduced white blood cell count in 23 (82%), thrombocytopenia in seven (25%), and anaemia in three (11%). Grade 4 neutropenia was reported in 22 (79%) patients after the first dose of prexasertib and was transient (median duration 6 days [IQR 4-8]) and recovered without growth-factor support in all cases. The treatment-related serious adverse event of grade 3 febrile neutropenia was reported in two (7%) patients. One patient died during the study due to tumour progression.

interpretationPrexasertib showed clinical activity and was tolerable in patients with BRCA wild-type high-grade serous ovarian carcinoma. This drug warrants further development in this setting, especially for patients with platinum-resistant or platinum-refractory disease.

fundingIntramural Research Program of the National Institutes of Health and National Cancer Institute.

Indexed as

AdultAgedBRCA1 ProteinBRCA2 ProteinCheckpoint Kinase 1Cystadenocarcinoma, SerousDisease-Free SurvivalFemaleHumansMiddle AgedNeoplasm InvasivenessNeoplasm Recurrence, LocalNeoplasm StagingOvarian NeoplasmsPrognosisPyrazinesBRCA1 ProteinBRCA2 ProteinCheckpoint Kinase 1prexasertibPyrazinesPyrazoles

Identifiers

PMID29361470
PMCPMC7366122
OpenAlexW2783907570

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.