Evidence map›Paper›PMID 27198170›Full record

ArticleCancer2016

A phase 1 study of buparlisib and bevacizumab in patients with metastatic renal cell carcinoma progressing on vascular endothelial growth factor-targeted therapies.

Rana R McKay, Guillermo De Velasco, Lillian Werner, Joaquim Bellmunt, Lauren Harshman, Christopher Sweeney, Jonathan E Rosenberg, Michelle Hirsch, Sabina Signoretti, Eliezer M Van Allen and 4 more

Abstract readClinical Trial, Phase IMulticenter Study
In one paragraph

Article in Cancer, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
2.0field-weighted citation impact, top 13% 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

12 citing papers in PubMed, 18 citations in OpenAlex.

  1. A randomized phase 2 study of MK-2206 versus everolimus in refractory renal cell carcinoma.Annals of oncology : official journal of the European Society for Medical Oncology · 2017
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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

14 authors at 5 institutions in 1 country.

Rana R McKayDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
Guillermo De VelascoDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
Lillian WernerDepartment of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, Massachusetts.
Joaquim BellmuntDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
Lauren HarshmanDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
Christopher SweeneyDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
Jonathan E RosenbergDeparment of Medical Oncology, Memorial Sloan Kettering Cancer Center, New York, New York.
Michelle HirschDepartment of Pathology, Brigham and Women's Hospital, Boston, Massachusetts.
Sabina SignorettiDepartment of Pathology, Brigham and Women's Hospital, Boston, Massachusetts.
Eliezer M Van AllenDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
Meghara WalshDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
Ulka VaishampayanDepartment of Hematology/Oncology, Karmanos Cancer Institute, Wayne State University, Detroit, Michigan.
David F McDermottDepartment of Medical Oncology, Beth Israel Deaconess Medical Center, Boston, Massachusetts.
Toni K ChoueiriDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
Dana-Farber Cancer Institute · USBrigham and Women's Hospital · USBeth Israel Deaconess Medical Center · USMemorial Sloan Kettering Cancer Center · USWayne State University · US

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Nicholas D Socci · 1985 to 2026
$347.4M
Treating the P13-Kinase/AKTP50CA101942 · NCI · BETH ISRAEL DEACONESS MEDICAL CENTER · PI Wanling Xie · 2003 to 2026
$53.4M
NCI NIH HHS P30 CA008748NCI NIH HHS P50 CA101942
6 · The paper itself

Abstract

backgroundThe phosphatidylinositol-3 kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway is dysregulated in patients with metastatic renal cell carcinoma (mRCC). Buparlisib is a pan-PI3K inhibitor with activity in advanced solid tumors. The primary objective of the current study was to determine the maximum tolerated dose (MTD) and dose-limiting toxicities of buparlisib and bevacizumab in patients with mRCC. Secondary objectives included efficacy, biomarker discovery, and additional toxicity.

methodsThis was a standard 3 + 3 dose escalation study of buparlisib (at a dose of 60-100 mg/day) and bevacizumab (at a dose of 10 mg/kg every 2 weeks). After the MTD was defined, 15 patients were accrued to the expansion cohort.

resultsThirty-two patients were accrued (3 were treated at 60 mg/day, 21 were treated at 80 mg/day, 6 were treated at 100 mg/day, and 2 patients never received therapy). The majority of patients had clear cell histology (87%) and 50% had received ≥2 prior lines of therapy. The MTD of buparlisib was 80 mg/day and that of bevacizumab was 10 mg/kg every 2 weeks. A total of 28 patients discontinued therapy: 17 because of disease progression, 7 because of toxicity, and 4 for other reasons. Dose-limiting toxicities included rash/pruritis, elevated lipase/amylase, anorexia, and psychiatric disorders (suicidal ideation, depression, and cognitive disturbances). Of the 30 patients who received at least 1 dose, 13% achieved a partial response (95% confidence interval, 4%-31%). Two patients harboring activating PI3KA mutations achieved 42% and 16% maximal tumor shrinkage, respectively.

conclusionsBuparlisib at a dose of 80 mg/day with bevacizumab was found to be a tolerable regimen with preliminary activity in vascular endothelial growth factor-refractory mRCC. The benefit of this combination may be of interest for future mRCC trials, possibly in a selected patient population. Cancer 2016;122:2389-2398. © 2016 American Cancer Society.

Indexed as

AminopyridinesAntineoplastic Combined Chemotherapy ProtocolsBevacizumabBiomarkersCarcinoma, Renal CellFemaleHumansKidney NeoplasmsMaleMolecular Targeted TherapyMorpholinesNeoplasm MetastasisTreatment OutcomeVascular Endothelial Growth Factor AAminopyridinesBevacizumabBiomarkersMorpholinesNVP-BKM120Vascular Endothelial Growth Factor Abevacizumabbuparlisibphase 1phosphatidylinositol-3 kinase (PI3K) inhibitorrenal cell carcinoma

Identifiers

PMID27198170
PMCPMC5567751
OpenAlexW2398348186

What OpenQuestion holds

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Registered trials

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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.