Evidence map›Paper›PMID 38672538›Full record

ArticleCancers2024

A Phase Ib Expansion Cohort Evaluating Aurora A Kinase Inhibitor Alisertib and Dual TORC1/2 Inhibitor Sapanisertib in Patients with Advanced Solid Tumors.

S Lindsey Davis, Wells A Messersmith, W Thomas Purcell, Elaine T Lam, Bradley R Corr, Alexis D Leal, Christopher H Lieu, Cindy L O'Bryant, Stephen G Smoots, Evan D Dus and 4 more

Open access · goldAbstract read
In one paragraph

Article in Cancers, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.7field-weighted citation impact, top 35% 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

3 citing papers in PubMed, 2 citations in OpenAlex.

  1. Review
  2. Article
  3. Role of c-Myc in lung cancer: Progress, challenges, and prospects.Chinese medical journal pulmonary and critical care medicine · 2023
    Article
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

14 authors at 3 institutions in 1 country.

S Lindsey DavisDivision of Medical Oncology, Department of Medicine, University of Colorado School of Medicine, Aurora, CO 80045, USA.
Wells A MessersmithDivision of Medical Oncology, Department of Medicine, University of Colorado School of Medicine, Aurora, CO 80045, USA.
W Thomas PurcellDivision of Hematology and Oncology, Department of Medicine, University of Washington School of Medicine, Seattle, WA 98195, USA.
Elaine T LamDivision of Medical Oncology, Department of Medicine, University of Colorado School of Medicine, Aurora, CO 80045, USA.ORCID 0000-0001-5629-3402
Bradley R CorrDivision of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Colorado School of Medicine, Aurora, CO 80045, USA.
Alexis D LealDivision of Medical Oncology, Department of Medicine, University of Colorado School of Medicine, Aurora, CO 80045, USA.
Christopher H LieuDivision of Medical Oncology, Department of Medicine, University of Colorado School of Medicine, Aurora, CO 80045, USA.
Cindy L O'BryantSkaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, CO 80045, USA.ORCID 0000-0001-6337-2221
Stephen G SmootsDivision of Medical Oncology, Department of Medicine, University of Colorado School of Medicine, Aurora, CO 80045, USA.
Evan D DusDivision of Medical Oncology, Department of Medicine, University of Colorado School of Medicine, Aurora, CO 80045, USA.
Kimberly R JordanDepartment of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, CO 80045, USA.
Natalie J SerkovaDepartment of Radiology, University of Colorado School of Medicine, Aurora, CO 80045, USA.
Todd M PittsDivision of Medical Oncology, Department of Medicine, University of Colorado School of Medicine, Aurora, CO 80045, USA.ORCID 0000-0002-8123-9894
Jennifer R DiamondDivision of Medical Oncology, Department of Medicine, University of Colorado School of Medicine, Aurora, CO 80045, USA.
University of Colorado Denver · USUniversity of Montana · USUniversity of Washington · US

Funding

University of Colorado Cancer Center Support Grant - Lung Cancer Patient-Derived Xenografts with Autologous Human Immune SystemsP30CA046934 · NCI · UNIVERSITY OF COLORADO DENVER · PI James V Degregori · 1988 to 2026
$117.0M
Paul Calabresis Award in Clinical Oncology ResearchK12CA086913 · NCI · UNIVERSITY OF COLORADO DENVER · PI VIRGINIA F. BORGES, Jill E Slansky · 2000 to 2026
$17.8M
NCI NIH HHS K12 CA086913NCI NIH HHS P30 CA046934Takeda Pharmaceuticals, to Jennifer R. Diamond No grant number
6 · The paper itself

Abstract

backgroundThis study further evaluated the safety and efficacy of the combination of alisertib and sapanisertib in an expansion cohort of patients, including a subset of patients with refractory pancreatic adenocarcinoma, with further evaluation of the pharmacodynamic characteristics of combination therapy.

methodsTwenty patients with refractory solid tumors and 11 patients with pancreatic adenocarcinoma were treated at the recommended phase 2 dose of alisertib and sapanisertib. Adverse events and disease response were assessed. Patients in the expansion cohort were treated with a 7-day lead-in of either alisertib or sapanisertib prior to combination therapy, with tumor tissue biopsy and serial functional imaging performed for correlative analysis.

resultsToxicity across treatment groups was overall similar to prior studies. One partial response to treatment was observed in a patient with ER positive breast cancer, and a patient with pancreatic cancer experienced prolonged stable disease. In an additional cohort of pancreatic cancer patients, treatment response was modest. Correlative analysis revealed variability in markers of apoptosis and immune cell infiltrate according to lead-in therapy and response.

conclusionsDual targeting of Aurora A kinase and mTOR resulted in marginal clinical benefit in a population of patients with refractory solid tumors, including pancreatic adenocarcinoma, though individual patients experienced significant response to therapy. Correlatives indicate apoptotic response and tumor immune cell infiltrate may affect clinical outcomes.

Indexed as

alisertibAurora A kinaseexpansion cohortmTORpancreatic adenocarcinomasapanisertibsolid tumors

Identifiers

PMID38672538
PMCPMC11048245
OpenAlexW4394693662

What OpenQuestion holds

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LicenceCC BY
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.