Evidence map›Paper›PMID 29882250›Full record

ArticleThe Prostate2018

A dose finding clinical trial of cabozantinib (XL184) administered in combination with abiraterone acetate in metastatic castration-resistant prostate cancer.

Atish D Choudhury, Kathryn P Gray, Jeffrey G Supko, Lauren C Harshman, Mary-Ellen Taplin, Amanda F Pace, Matthew Farina, Katherine A Zukotynski, Brandon Bernard, Philip W Kantoff and 2 more

Open access · greenAbstract read
In one paragraph

Article in The Prostate, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.5field-weighted citation impact, top 30% 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

4 citing papers in PubMed, 4 citations in OpenAlex.

  1. Review
  2. Review
  3. Review
  4. 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

12 authors at 6 institutions in 2 countries.

Atish D ChoudhuryDana-Farber Cancer Institute, Boston, Massachusetts.ORCID http://orcid.org/0000-0001-9344-6631
Kathryn P GrayDana-Farber Cancer Institute, Boston, Massachusetts.
Jeffrey G SupkoMassachusetts General Hospital, Boston, Massachusetts.
Lauren C HarshmanDana-Farber Cancer Institute, Boston, Massachusetts.ORCID http://orcid.org/0000-0002-7636-1588
Mary-Ellen TaplinDana-Farber Cancer Institute, Boston, Massachusetts.
Amanda F PaceDana-Farber Cancer Institute, Boston, Massachusetts.
Matthew FarinaDana-Farber Cancer Institute, Boston, Massachusetts.
Katherine A ZukotynskiMcMaster University, Hamilton, Ontario, Canada.
Brandon BernardUniversity of Colorado Denver, Denver, Colorado.
Philip W KantoffMemorial Sloan-Kettering Cancer Center, New York, New York.
Mark PomerantzDana-Farber Cancer Institute, Boston, Massachusetts.
Christopher SweeneyDana-Farber Cancer Institute, Boston, Massachusetts.
Harvard University · USDana-Farber Cancer Institute · USMassachusetts General Hospital · USMcMaster University · CAMemorial Sloan Kettering Cancer Center · USUniversity of Colorado Denver · US

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Hongbiao Carl Lekaye · 1985 to 2026
$347.4M
VectorP30CA006516 · NCI · DANA-FARBER CANCER INSTITUTE · PI JENNIFER W MACK · 1985 to 2026
$330.6M
Tumor and Circulating Markers as Links Between Obesity and Lethal Prostate CanceP50CA090381 · NCI · DANA-FARBER CANCER INSTITUTE · PI KANTOFF, PHILIP W · 2002 to 2017
$36.2M
NCI NIH HHS P30 CA006516NCI NIH HHS P30 CA008748NCI NIH HHS P50 CA090381
6 · The paper itself

Abstract

backgroundCabozantinib can enhance the effect of abiraterone in preclinical prostate cancer models. This study aimed to define the recommended phase 2 dose (RP2D) and preliminary efficacy of abiraterone + cabozantinib in mCRPC.

methodsPatients with progressive mCRPC with 0-2 prior chemotherapy regimens but no prior CYP17A1 or MET inhibitor received abiraterone acetate at 1000 mg daily with prednisone 5 mg BID in combination with cabozantinib at 20, 40, or 60 mg daily in a dose-escalation 3 + 3 open-label phase 1 design (Part A). After tolerable doses were defined, cohorts were expanded to better define toxicity and efficacy (Part B).

resultsThere were no dose-limiting toxicities (DLTs) in the first 4 weeks at any of the three dose levels in Part A. Two of the three patients at the 60 mg dose level required dose reductions beyond cycle 2 due to fatigue. In Part B, nine more patients were accrued to each of the 20 and 40 mg doses. Of the 12 patients treated at the 40 mg dose, only one DLT (grade 3 Lipase elevation) was observed in cycle 1. The median time to radiographic progression was 12.88 months (95% CI:5.42- not estimated [NE]) in the 20 mg cohort and 22.01 months (95% CI:15.44-NE) in the 40 mg cohort. Median overall survival was 23.29 months (95% CI:19.06-NE) in the 20 mg cohort and 39.08 months (95% CI:17.38-NE) in the 40 mg cohort.

conclusionsBased on tolerability and preliminary efficacy, 40 mg cabozantinib plus 1000 mg abiraterone daily is the RP2D.

Indexed as

abirateronecabozantinibcastration-resistantprostate cancerXL184

Identifiers

PMID29882250
PMCPMC6286224
OpenAlexW2807386738

What OpenQuestion holds

Textmetadata
LicenceTDM
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.