Evidence map›Paper›PMID 35171658›Full record

Trial reportJCO precision oncology2022

Biomarker-Based Phase II Study of Sapanisertib (TAK-228): An mTORC1/2 Inhibitor in Patients With Refractory Metastatic Renal Cell Carcinoma.

Bradley A McGregor, Wanling Xie, Elio Adib, Walter M Stadler, Yousef Zakharia, Aijai Alva, M Dror Michaelson, Shilpa Gupta, Elaine T Lam, Subrina Farah and 9 more

Registry-linked trialOpen access · greenAbstract readClinical Trial, Phase IIMulticenter Study
In one paragraph

Trial report in JCO precision oncology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03097328 (A Phase II Study of TAK-228 In Patients With Previously Treated Metastatic Renal Cell Carcinoma), which is not on this map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
1.4field-weighted citation impact, top 19% 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.

NCT03097328 phase2completednot on this map

A Phase II Study of TAK-228 In Patients With Previously Treated Metastatic Renal Cell Carcinoma

TypeinterventionalSponsorBradley A. McGregor, MDRan2017 to 2024Enrolled39ConditionsRenal Cell CarcinomaArmsTAK-228
3 · Its place in the literature

Who cites it

9 citing papers in PubMed, 10 citations in OpenAlex.

  1. Article
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  4. Review
  5. Review
  6. Article
  7. Review
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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

19 authors at 9 institutions in 1 country.

Bradley A McGregorDana-Farber Cancer Institute, Boston, MA.ORCID 0000-0002-8298-0289
Wanling XieDana-Farber Cancer Institute, Boston, MA.ORCID 0000-0001-5995-8000
Elio AdibDana-Farber Cancer Institute, Boston, MA.
Walter M StadlerUniversity of Chicago, Chicago, IL.ORCID 0000-0002-0435-2527
Yousef ZakhariaUniversity of Iowa, Iowa City, IA.
Aijai AlvaUniversity of Michigan, Ann Arbor, MI.
M Dror MichaelsonMassachusetts General Hospital, Boston, MA.ORCID 0000-0001-9249-6338
Shilpa GuptaCleveland Clinic, Cleveland, OH.ORCID 0000-0002-8775-503X
Elaine T LamUniversity of Colorado Cancer Center, Aurora, CO.
Subrina FarahDana-Farber Cancer Institute, Boston, MA.
Amin H NassarDana-Farber Cancer Institute, Boston, MA.ORCID 0000-0002-8084-9105
Xiao X WeiDana-Farber Cancer Institute, Boston, MA.
Kerry L KilbridgeDana-Farber Cancer Institute, Boston, MA.
Lauren HarshmanDana-Farber Cancer Institute, Boston, MA.ORCID 0000-0002-7636-1588
Sabina SignorettiBrigham and Women's Hospital, Boston, MA.ORCID 0000-0002-5000-9105
Lynette ShollBrigham and Women's Hospital, Boston, MA.ORCID 0000-0002-9532-9735
David J KwiatkowskiDana-Farber Cancer Institute, Boston, MA.ORCID 0000-0002-5668-5219
Rana R McKayUniversity of California San Diego, San Diego, CA.ORCID 0000-0002-0581-7963
Toni K ChoueiriDana-Farber Cancer Institute, Boston, MA.ORCID 0000-0002-9201-3217
Dana-Farber Cancer Institute · USBrigham and Women's Hospital · USCleveland Clinic · USMassachusetts General Hospital · USUniversity of California San Diego · USUniversity of Chicago · USUniversity of Colorado Cancer Center · USUniversity of Iowa · USUniversity of Michigan · US

Funding

Treating the P13-Kinase/AKTP50CA101942 · NCI · BETH ISRAEL DEACONESS MEDICAL CENTER · PI Wanling Xie · 2003 to 2026
$53.4M
Developing a Translation Pipeline for VHL Mutant MalignanciesU01CA236489 · NCI · BETH ISRAEL DEACONESS MEDICAL CENTER · PI David McDermott · 2019 to 2026
$3.8M
NCI NIH HHS P50 CA101942NCI NIH HHS U01 CA236489
6 · The paper itself

Abstract

purposeSapanisertib is a kinase inhibitor that inhibits both mammalian target of rapamycin complex 1 (mTORC1) and mTORC2. In this multicenter, single-arm phase II trial, we evaluated the efficacy of sapanisertib in patients with treatment-refractory metastatic renal cell carcinoma (mRCC; NCT03097328).

methodsPatients with mRCC of any histology progressing through standard therapy (including prior mTOR inhibitors) had baseline biopsy and received sapanisertib 30 mg by mouth once weekly until unacceptable toxicity or disease progression. The primary end point was objective response rate by RECIST 1.1. Tissue biomarkers of mTOR pathway activation were explored.

resultsWe enrolled 38 patients with mRCC (clear cell = 28; variant histology = 10) between August 2017 and November 2019. Twenty-four (63%) had received ≥ 3 prior lines of therapy; 17 (45%) had received prior rapalog therapy. The median follow-up was 10.4 (range 1-27.4) months. Objective response rate was two of 38 (5.3%; 90% CI, 1 to 15.6); the median progression-free survival (PFS) was 2.5 months (95% CI, 1.8 to 3.7). Twelve patients (32%) developed treatment-related grade 3 adverse events, with no grade 4 or 5 toxicities. Alterations in the mTOR pathway genes were seen in 5 of 29 evaluable patients (

conclusionSapanisertib had minimal activity in treatment-refractory mRCC independent of mTOR pathway alterations. Additional therapeutic strategies are needed for patients with refractory mRCC.

Indexed as

Carcinoma, Renal CellKidney NeoplasmsAdenineBenzoxazolesBiomarkersHumansMechanistic Target of Rapamycin Complex 1PyrazolesPyrimidinesAdenineBenzoxazolesBiomarkersMechanistic Target of Rapamycin Complex 1PyrazolesPyrimidinessapanisertib

Identifiers

PMID35171658
PMCPMC8865529
OpenAlexW4213321838

What OpenQuestion holds

Textmetadata
Read underepoch 390

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.