Evidence map›Paper›PMID 30514390›Full record

ArticleJournal for immunotherapy of cancer2018

Activity of durvalumab plus olaparib in metastatic castration-resistant prostate cancer in men with and without DNA damage repair mutations.

Fatima Karzai, David VanderWeele, Ravi A Madan, Helen Owens, Lisa M Cordes, Amy Hankin, Anna Couvillon, Erin Nichols, Marijo Bilusic, Michael L Beshiri and 17 more

Registry-linked trialOpen access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal for immunotherapy of cancer, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02484404 (Phase I/II Study of the Anti-Programmed Death Ligand-1 Antibody Durvalumab), which is not on this map. Cited by 182 papers, 16 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
182citing papers in PubMed, 16 pooled it
13.4field-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.

NCT02484404 phase1 / phase2active not recruitingnot on this map

Phase I/II Study of the Anti-Programmed Death Ligand-1 Antibody Durvalumab (MEDI4736) in Combination With Olaparib and/or Cediranib for Advanced Solid Tumors and Advanced or Recurrent Ovarian, Triple Negative Breast, Lung, Prostate and Colorectal Cancers

TypeinterventionalSponsorNational Cancer Institute (NCI)Ran2015 to 2027Enrolled268ConditionsColorectal Neoplasms, Breast NeoplasmsArmsOlaparib, Cediranib, Durvalumab
3 · Its place in the literature

Who cites it

182 citing papers in PubMed, 16 syntheses or guidelines pooled it, 309 citations in OpenAlex.

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  6. Immune checkpoint inhibitor-related hearing loss: a systematic review and analysis of individual patient data.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2023
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122 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

27 authors at 6 institutions in 2 countries.

Fatima KarzaiGenitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
David VanderWeeleLaboratory of Genitourinary Cancer Pathogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Ravi A MadanGenitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Helen OwensGenitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Lisa M CordesGenitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Amy HankinGenitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Anna CouvillonGenitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Erin NicholsClinical Research Directorate/Clinical Monitoring Research Program, Leidos Biomedical Research, Inc., NCI Campus at Frederick, Frederick, MD, USA.
Marijo BilusicGenitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Michael L BeshiriLaboratory of Genitourinary Cancer Pathogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Kathleen KellyLaboratory of Genitourinary Cancer Pathogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Venkatesh KrishnasamyDepartment of Radiology and Imaging Sciences, Center for Cancer Research, National Institutes of Health, Bethesda, MD, USA.
Sunmin LeeDevelopmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Min-Jung LeeDevelopmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Akira YunoDevelopmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Jane B TrepelDevelopmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Maria J MerinoLaboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Ryan DittamoreEpic Sciences Inc., San Diego, CA, USA.
Jennifer MartéGenitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Renee N DonahueLaboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Jeffrey SchlomLaboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Keith J KillianGenetics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Paul S MeltzerGenetics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Seth M SteinbergBiostatistics and Data Management Section, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
James L GulleyGenitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Jung-Min LeeWomen's Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
William L DahutGenitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. dahutw@mail.nih.gov.
National Institutes of Health · USNational Cancer Institute · USCenter for Cancer Research · USCancer Institute (WIA) · INEpic Sciences (United States) · USLeidos Biomedical Research Inc. (United States)

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
NCI NIH HHS HHSN261200800001E
6 · The paper itself

Abstract

backgroundCheckpoint inhibitors have not been effective for prostate cancer as single agents. Durvalumab is a human IgG1-K monoclonal antibody that targets programmed death ligand 1 and is approved by the U.S. Food and Drug Administration for locally advanced or metastatic urothelial cancer and locally advanced, unresectable stage 3 non-small cell lung cancer. Olaparib, a poly (ADP-ribose) polymerase inhibitor, has demonstrated an improvement in median progression-free survival (PFS) in select patients with metastatic castration-resistant prostate cancer (mCRPC). Data from other trials suggest there may be improved activity in men with DNA damage repair (DDR) mutations treated with checkpoint inhibitors. This trial evaluated durvalumab and olaparib in patients with mCRPC with and without somatic or germline DDR mutations.

methodsEligible patients had received prior enzalutamide and/or abiraterone. Patients received durvalumab 1500 mg i.v. every 28 days and olaparib 300 mg tablets p.o. every 12 h until disease progression or unacceptable toxicity. All patients had biopsies of metastatic lesions with an evaluation for both germline and somatic mutations.

resultsSeventeen patients received durvalumab and olaparib. Nausea was the only nonhematologic grade 3 or 4 toxicity occurring in > 1 patient (2/17). No patients were taken off trial for toxicity. Median radiographic progression-free survival (rPFS) for all patients is 16.1 months (95% CI: 4.5-16.1 months) with a 12-month rPFS of 51.5% (95% CI: 25.7-72.3%). Activity is seen in patients with alterations in DDR genes, with a median rPFS of 16.1 months (95% CI: 7.8-18.1 months). Nine of 17 (53%) patients had a radiographic and/or PSA response. Patients with fewer peripheral myeloid-derived suppressor cells and with alterations in DDR genes were more likely to respond. Early changes in circulating tumor cell counts and in both innate and adaptive immune characteristics were associated with response.

conclusionsDurvalumab plus olaparib has acceptable toxicity, and the combination demonstrates efficacy, particularly in men with DDR abnormalities.

trial registrationClinicalTrials.gov identifier: NCT02484404 .

Indexed as

DNA DamageDNA RepairMutationAntibodies, MonoclonalAntineoplastic Combined Chemotherapy ProtocolsCombined Modality TherapyHumansKaplan-Meier EstimateMaleNeoplasm GradingNeoplasm MetastasisNeoplasm StagingPhthalazinesPiperazinesProstatic Neoplasms, Castration-ResistantRetreatmentAntibodies, MonoclonaldurvalumabolaparibPhthalazinesPiperazinesAbirateroneAnti-PD-L1DurvalumabEnzalutamideImmunotherapymCRPCOlaparibPARP inhibitor

Identifiers

PMID30514390
PMCPMC6280368
OpenAlexW2902703786

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.