Evidence map›Paper›PMID 42636061›Full record

Trial reportCancer research communications2026

A Phase II Study of Berzosertib in Combination with Carboplatin Compared with Docetaxel with Carboplatin in Metastatic Castration-Resistant Prostate Cancer.

Atish D Choudhury, Caiwei Zhong, Wanling Xie, Bose S Kochupurakkal, Peter I-Fan Wu, Irbaz Bin Riaz, Ruolin Liu, David D Yang, Edmund Folefac, Daniel Lee and 16 more

Abstract readClinical Trial, Phase IIRandomized Controlled TrialComparative Study
In one paragraph

Trial report in Cancer research communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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

1 citing paper in PubMed.

  1. Review
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

26 authors.

Atish D ChoudhuryDana-Farber Cancer Institute , Boston, Massachusetts.ORCID 0000-0001-9344-6631
Caiwei ZhongDana-Farber Cancer Institute , Boston, Massachusetts.ORCID 0009-0002-9561-1439
Wanling XieDana-Farber Cancer Institute , Boston, Massachusetts.ORCID 0000-0001-5995-8000
Bose S KochupurakkalDana-Farber Cancer Institute , Boston, Massachusetts.ORCID 0000-0001-8929-3070
Peter I-Fan WuMolecular Characterization Laboratory, Frederick National Laboratory for Cancer Research, Frederick, Maryland.ORCID 0000-0001-5570-4871
Irbaz Bin RiazMayo Clinic, Phoenix, Arizona.ORCID 0000-0003-4249-0311
Ruolin LiuBroad Institute of MIT and Harvard , Cambridge, Massachusetts.ORCID 0000-0001-9059-6335
David D YangDana-Farber Cancer Institute , Boston, Massachusetts.ORCID 0000-0002-5146-218X
Edmund FolefacThe Ohio State University Comprehensive Cancer Center, Columbus, Ohio.ORCID 0000-0001-5510-7073
Daniel LeeUniversity of Pittsburgh , Pittsburgh, Pennsylvania.ORCID 0000-0003-4411-3595
Mamta ParikhUC Davis Comprehensive Cancer Center, Sacramento, California.ORCID 0000-0002-7300-7452
David J EinsteinBeth Israel Deaconess Medical Center , Boston, Massachusetts.ORCID 0000-0001-9163-3281
Elizabeth R KesslerUniversity of Colorado Hospital Cancer Center, Aurora, Colorado.ORCID 0000-0001-7285-867X
Tina MayerRutgers Cancer Institute of New Jersey , New Brunswick, New Jersey.ORCID 0000-0003-0078-3773
Rana R McKayUniversity of California San Diego Moores Cancer Center , La Jolla, California.ORCID 0000-0002-0581-7963
Amanda PaceDana-Farber Cancer Institute , Boston, Massachusetts.ORCID 0000-0001-5360-4105
Kent W MouwDana-Farber Cancer Institute , Boston, Massachusetts.ORCID 0000-0001-7939-7343
Li ChenMolecular Characterization Laboratory, Frederick National Laboratory for Cancer Research, Frederick, Maryland.ORCID 0000-0001-7973-5912
Viktor A AdalsteinssonBroad Institute of MIT and Harvard , Cambridge, Massachusetts.ORCID 0000-0003-4555-2485
Eliezer M Van AllenDana-Farber Cancer Institute , Boston, Massachusetts.ORCID 0000-0002-0201-4444
Charles A KunosMarkey Cancer Center , University of Kentucky, Lexington, Kentucky.ORCID 0009-0004-4056-9004
Steven D GoreCancer Therapy Evaluation Program, National Cancer Institute, Rockville, Maryland.ORCID 0009-0007-2139-5653
Biswajit DasMolecular Characterization Laboratory, Frederick National Laboratory for Cancer Research, Frederick, Maryland.ORCID 0000-0001-7225-2926
Alan D'AndreaDana-Farber Cancer Institute , Boston, Massachusetts.ORCID 0000-0001-6168-6294
Mary-Ellen TaplinDana-Farber Cancer Institute , Boston, Massachusetts.ORCID 0000-0002-3384-0300
Geoffrey I ShapiroDana-Farber Cancer Institute , Boston, Massachusetts.ORCID 0000-0002-3331-4095

Funding

XPO1 inhibitors Selinexor and Eltanexor in Combination with Venetoclax and Decitabine (ASTX727) in AMLUM1CA186709 · NCI · DANA-FARBER CANCER INST · PI KEITH T FLAHERTY, DONALD W. KUFE · 2014 to 2026
$25.9M
Merck KGaA (Merck) Supplied berzosertib via the NCI Pharmaceutical Management BranchNational Cancer Institute (NCI) Biomarker supplement to UM1 CA186709National Cancer Institute (NCI) CTEP protocol 10191National Cancer Institute (NCI) UM1 CA186709NCI NIH HHS UM1 CA186709U.S. Department of War (DOW) CDMRP PCRP Translational Science Award PC190196 -U.S. Department of War (DOW) Grant 12907103
6 · The paper itself

Abstract

purposeInhibitors of the ataxia-telangiectasia and Rad3-related (ATR) protein kinase, a critical component of the DNA damage repair response, have synergistic anticancer activity with platinum compounds in preclinical models. We therefore conducted a phase II study of the ATR inhibitor berzosertib + carboplatin versus docetaxel + carboplatin in metastatic castration-resistant prostate cancer (mCRPC). PATIENTS AND

methodsPatients previously treated with at least one androgen receptor pathway inhibitor and taxane underwent mandatory biopsy and were randomized 1:1 to receive arm A (docetaxel 60 mg/m2 + carboplatin AUC4 day 1 or carboplatin AUC5 if not a docetaxel candidate) or arm B (berzosertib 90 mg/m2 days 2 and 9 + carboplatin AUC5 day 1) every 21 days. The primary endpoint was overall response rate (ORR; ≥50% PSA decline or radiographic response).

resultsOf 73 randomized patients, 65 received protocol treatment: 34 on arm A (26 docetaxel + carboplatin and 8 carboplatin alone) and 31 on arm B. Thirteen patients (38%) in arm A and 20 (65%) in arm B had ≥ grade 3 treatment-related adverse events (TrAE). ORR was 15% in arm A [5/34; 5/26 (19%) with docetaxel + carboplatin] and 0% in arm B (0/31). At interim analysis, after 65 of the planned 130 patients were treated, enrollment was halted due to futility. Homologous recombination repair (HRR) deficiency status from tissue and blood did not correlate with clinical outcomes, but ATM deficiency or high levels of phospho-Krüppel-associated box (KRAB) domain-associated protein 1 (pKAP1) detected in tissue were associated with clinical benefit across both arms of the trial.

conclusionsBerzosertib + carboplatin demonstrated lower ORR and more frequent ≥ grade 3 TrAEs compared with docetaxel + carboplatin in this heavily pretreated, biomarker-unselected population. SIGNIFICANCE: The combination of the ATR inhibitor berzosertib with carboplatin demonstrated a lower ORR compared with docetaxel with carboplatin in a heavily pretreated biomarker-unselected mCRPC population. Assays for HRR deficiency showed limited predictive capability, but a combined tissue biomarker of ATM deficiency and elevated pKAP1 (indicating elevated replication stress) was associated with benefit in both study arms and warrants investigation for benefit from carboplatin-based therapy.

Indexed as

Antineoplastic Combined Chemotherapy ProtocolsCarboplatinDocetaxelProstatic Neoplasms, Castration-ResistantAgedAged, 80 and overAtaxia Telangiectasia Mutated ProteinsHumansIsoxazolesMaleMiddle AgedPyrazinesAtaxia Telangiectasia Mutated ProteinsberzosertibCarboplatinDocetaxelIsoxazolesPyrazines

Identifiers

PMID42636061
PMCPMC13586805

What OpenQuestion holds

Textmetadata
Read underepoch 390

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.