Evidence map›Paper›PMID 24842883›Full record

ArticleJournal of the National Cancer Institute2014

Phase I/Ib study of olaparib and carboplatin in BRCA1 or BRCA2 mutation-associated breast or ovarian cancer with biomarker analyses.

Jung-Min Lee, John L Hays, Christina M Annunziata, Anne M Noonan, Lori Minasian, Jo Anne Zujewski, Minshu Yu, Nicolas Gordon, Jiuping Ji, Tristan M Sissung and 5 more

Registry-linked trialOpen access · bronzeAbstract readClinical Trial, Phase I
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of the National Cancer Institute, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02326844 (A Phase 2 Pilot Study of BMN 673), which is not on this map. Cited by 104 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
104citing papers in PubMed, 1 pooled it
12.4field-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.

NCT02326844 phase2terminatednot on this mapstarted 2015, after this paper: background citation

A Phase 2 Pilot Study of BMN 673 (Talazoparib), an Oral PARP Inhibitor, in Patients With Deleterious BRCA1/2 Mutation-Associated Ovarian Cancer Who Have Had Prior PARP Inhibitor Treatment

TypeinterventionalSponsorNational Cancer Institute (NCI)Ran2015 to 2016Enrolled3ConditionsOvarian CancerArmsBMN 673 (talazoparib)
3 · Its place in the literature

Who cites it

104 citing papers in PubMed, 1 synthesis or guideline pooled it, 183 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Efficacy of the PARP Inhibitor Veliparib with Carboplatin or as a Single Agent in Patients with GermlineClinical cancer research : an official journal of the American Association for Cancer Research · 2017
    Trial
  4. Sequence-Specific Pharmacokinetic and Pharmacodynamic Phase I/Ib Study of Olaparib Tablets and Carboplatin in Women's Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2017
    Trial
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44 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors at 1 institution in 1 country.

Jung-Min LeeAffiliations of authors: Medical Oncology Branch, Center for Cancer Research (J-ML, JLH, CMA, AMN, LM, JAZ, MY, NG, TMS, WDF, NA, ECK), National Clinical Target Validation Laboratory, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research (JJ), Center for Interventional Oncology, Radiology, and Imaging Sciences, Clinical Center and National Cancer Institute (BJW), and Division of Cancer Treatment and Diagnosis, National Cancer Institute (JD), National Institutes of Health, Bethesda, MD. leej6@mail.nih.gov.
John L HaysAffiliations of authors: Medical Oncology Branch, Center for Cancer Research (J-ML, JLH, CMA, AMN, LM, JAZ, MY, NG, TMS, WDF, NA, ECK), National Clinical Target Validation Laboratory, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research (JJ), Center for Interventional Oncology, Radiology, and Imaging Sciences, Clinical Center and National Cancer Institute (BJW), and Division of Cancer Treatment and Diagnosis, National Cancer Institute (JD), National Institutes of Health, Bethesda, MD.
Christina M AnnunziataAffiliations of authors: Medical Oncology Branch, Center for Cancer Research (J-ML, JLH, CMA, AMN, LM, JAZ, MY, NG, TMS, WDF, NA, ECK), National Clinical Target Validation Laboratory, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research (JJ), Center for Interventional Oncology, Radiology, and Imaging Sciences, Clinical Center and National Cancer Institute (BJW), and Division of Cancer Treatment and Diagnosis, National Cancer Institute (JD), National Institutes of Health, Bethesda, MD.
Anne M NoonanAffiliations of authors: Medical Oncology Branch, Center for Cancer Research (J-ML, JLH, CMA, AMN, LM, JAZ, MY, NG, TMS, WDF, NA, ECK), National Clinical Target Validation Laboratory, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research (JJ), Center for Interventional Oncology, Radiology, and Imaging Sciences, Clinical Center and National Cancer Institute (BJW), and Division of Cancer Treatment and Diagnosis, National Cancer Institute (JD), National Institutes of Health, Bethesda, MD.
Lori MinasianAffiliations of authors: Medical Oncology Branch, Center for Cancer Research (J-ML, JLH, CMA, AMN, LM, JAZ, MY, NG, TMS, WDF, NA, ECK), National Clinical Target Validation Laboratory, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research (JJ), Center for Interventional Oncology, Radiology, and Imaging Sciences, Clinical Center and National Cancer Institute (BJW), and Division of Cancer Treatment and Diagnosis, National Cancer Institute (JD), National Institutes of Health, Bethesda, MD.
Jo Anne ZujewskiAffiliations of authors: Medical Oncology Branch, Center for Cancer Research (J-ML, JLH, CMA, AMN, LM, JAZ, MY, NG, TMS, WDF, NA, ECK), National Clinical Target Validation Laboratory, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research (JJ), Center for Interventional Oncology, Radiology, and Imaging Sciences, Clinical Center and National Cancer Institute (BJW), and Division of Cancer Treatment and Diagnosis, National Cancer Institute (JD), National Institutes of Health, Bethesda, MD.
Minshu YuAffiliations of authors: Medical Oncology Branch, Center for Cancer Research (J-ML, JLH, CMA, AMN, LM, JAZ, MY, NG, TMS, WDF, NA, ECK), National Clinical Target Validation Laboratory, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research (JJ), Center for Interventional Oncology, Radiology, and Imaging Sciences, Clinical Center and National Cancer Institute (BJW), and Division of Cancer Treatment and Diagnosis, National Cancer Institute (JD), National Institutes of Health, Bethesda, MD.
Nicolas GordonAffiliations of authors: Medical Oncology Branch, Center for Cancer Research (J-ML, JLH, CMA, AMN, LM, JAZ, MY, NG, TMS, WDF, NA, ECK), National Clinical Target Validation Laboratory, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research (JJ), Center for Interventional Oncology, Radiology, and Imaging Sciences, Clinical Center and National Cancer Institute (BJW), and Division of Cancer Treatment and Diagnosis, National Cancer Institute (JD), National Institutes of Health, Bethesda, MD.
Jiuping JiAffiliations of authors: Medical Oncology Branch, Center for Cancer Research (J-ML, JLH, CMA, AMN, LM, JAZ, MY, NG, TMS, WDF, NA, ECK), National Clinical Target Validation Laboratory, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research (JJ), Center for Interventional Oncology, Radiology, and Imaging Sciences, Clinical Center and National Cancer Institute (BJW), and Division of Cancer Treatment and Diagnosis, National Cancer Institute (JD), National Institutes of Health, Bethesda, MD.
Tristan M SissungAffiliations of authors: Medical Oncology Branch, Center for Cancer Research (J-ML, JLH, CMA, AMN, LM, JAZ, MY, NG, TMS, WDF, NA, ECK), National Clinical Target Validation Laboratory, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research (JJ), Center for Interventional Oncology, Radiology, and Imaging Sciences, Clinical Center and National Cancer Institute (BJW), and Division of Cancer Treatment and Diagnosis, National Cancer Institute (JD), National Institutes of Health, Bethesda, MD.
William D FiggAffiliations of authors: Medical Oncology Branch, Center for Cancer Research (J-ML, JLH, CMA, AMN, LM, JAZ, MY, NG, TMS, WDF, NA, ECK), National Clinical Target Validation Laboratory, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research (JJ), Center for Interventional Oncology, Radiology, and Imaging Sciences, Clinical Center and National Cancer Institute (BJW), and Division of Cancer Treatment and Diagnosis, National Cancer Institute (JD), National Institutes of Health, Bethesda, MD.
Nilofer AzadAffiliations of authors: Medical Oncology Branch, Center for Cancer Research (J-ML, JLH, CMA, AMN, LM, JAZ, MY, NG, TMS, WDF, NA, ECK), National Clinical Target Validation Laboratory, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research (JJ), Center for Interventional Oncology, Radiology, and Imaging Sciences, Clinical Center and National Cancer Institute (BJW), and Division of Cancer Treatment and Diagnosis, National Cancer Institute (JD), National Institutes of Health, Bethesda, MD.
Bradford J WoodAffiliations of authors: Medical Oncology Branch, Center for Cancer Research (J-ML, JLH, CMA, AMN, LM, JAZ, MY, NG, TMS, WDF, NA, ECK), National Clinical Target Validation Laboratory, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research (JJ), Center for Interventional Oncology, Radiology, and Imaging Sciences, Clinical Center and National Cancer Institute (BJW), and Division of Cancer Treatment and Diagnosis, National Cancer Institute (JD), National Institutes of Health, Bethesda, MD.
James DoroshowAffiliations of authors: Medical Oncology Branch, Center for Cancer Research (J-ML, JLH, CMA, AMN, LM, JAZ, MY, NG, TMS, WDF, NA, ECK), National Clinical Target Validation Laboratory, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research (JJ), Center for Interventional Oncology, Radiology, and Imaging Sciences, Clinical Center and National Cancer Institute (BJW), and Division of Cancer Treatment and Diagnosis, National Cancer Institute (JD), National Institutes of Health, Bethesda, MD.
Elise C KohnAffiliations of authors: Medical Oncology Branch, Center for Cancer Research (J-ML, JLH, CMA, AMN, LM, JAZ, MY, NG, TMS, WDF, NA, ECK), National Clinical Target Validation Laboratory, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research (JJ), Center for Interventional Oncology, Radiology, and Imaging Sciences, Clinical Center and National Cancer Institute (BJW), and Division of Cancer Treatment and Diagnosis, National Cancer Institute (JD), National Institutes of Health, Bethesda, MD.
National Institutes of Health · US

Funding

Institute for Clinical and Translational ResearchUL1TR001079 · NCATS · JOHNS HOPKINS UNIVERSITY · PI FORD, DANIEL ERNEST · 2013 to 2017
$60.1M
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
Interventional OncologyZIACL040015 · CLC · CLINICAL CENTER · PI WOOD, BRADFORD · 2009 to 2025
$0k
Intramural NIH HHSNCATS NIH HHS UL1 TR001079NCI NIH HHS HHSN261200800001E
6 · The paper itself

Abstract

backgroundOlaparib has single-agent activity against breast/ovarian cancer (BrCa/OvCa) in germline BRCA1 or BRCA2 mutation carriers (gBRCAm). We hypothesized addition of olaparib to carboplatin can be administered safely and yield preliminary clinical activity.

methodsEligible patients had measurable or evaluable disease, gBRCAm, and good end-organ function. A 3 + 3 dose escalation tested daily oral capsule olaparib (100 or 200mg every 12 hours; dose level1 or 2) with carboplatin area under the curve (AUC) on day 8 (AUC3 day 8), then every 21 days. For dose levels 3 to 6, patients were given olaparib days 1 to 7 at 200 and 400 mg every 12 hours, with carboplatin AUC3 to 5 on day 1 or 2 every 21 days; a maximum of eight combination cycles were permitted, after which daily maintenance of olaparib 400mg every12 hours continued until progression. Dose-limiting toxicity was defined in the first two cycles. Peripheral blood mononuclear cells were collected for polymorphism analysis and polyADP-ribose incorporation. Paired tumor biopsies (before/after cycle 1) were obtained for biomarker proteomics and apoptosis endpoints.

resultsForty-five women (37 OvCa/8 BrCa) were treated. Dose-limiting toxicity was not reached on the intermittent schedule. Expansion proceeded with olaparib 400mg every 12 hours on days 1 to 7/carboplatin AUC5. Grade 3/4 adverse events included neutropenia (42.2%), thrombocytopenia (20.0%), and anemia (15.6%). Responses included 1 complete response (1 BrCa; 23 months) and 21 partial responses (50.0%; 15 OvCa; 6 BrCa; median = 16 [4 to >45] in OvCa and 10 [6 to >40] months in BrCa). Proteomic analysis suggests high pretreatment pS209-eIF4E and FOXO3a correlated with duration of response (two-sided P < .001; Pearson's R (2) = 0.94).

conclusionsOlaparib capsules 400mg every 12 hours on days 1 to 7/carboplatin AUC5 is safe and has activity in gBRCAm BrCa/OvCa patients. Exploratory translational studies indicate pretreatment tissue FOXO3a expression may be predictive for response to therapy, requiring prospective validation.

Indexed as

MutationAdministration, OralAdultAgedAntineoplastic Combined Chemotherapy ProtocolsBRCA1 ProteinBRCA2 ProteinBreast NeoplasmsCarboplatinDrug Administration ScheduleFemaleForkhead Box Protein O3Forkhead Transcription FactorsGene Expression Regulation, NeoplasticGenetic Predisposition to DiseaseHumansBRCA1 ProteinBRCA1 protein, humanBRCA2 ProteinBRCA2 protein, humanCarboplatinForkhead Box Protein O3Forkhead Transcription FactorsFOXO3 protein, humanolaparibPhthalazinesPiperazinesPoly Adenosine Diphosphate Ribose

Identifiers

PMID24842883
PMCPMC4049120
OpenAlexW2117639046

What OpenQuestion holds

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Registered trials

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.