Evidence map›Paper›PMID 22692704›Full record

Trial reportCancer2012

AMG 386 in combination with sorafenib in patients with metastatic clear cell carcinoma of the kidney: a randomized, double-blind, placebo-controlled, phase 2 study.

Brian Rini, Cezary Szczylik, Nizar M Tannir, Piotr Koralewski, Piotr Tomczak, Andrzej Deptala, Luc Y Dirix, Mayer Fishman, Rodryg Ramlau, Alain Ravaud and 6 more

Open access · bronzeAbstract readClinical Trial, Phase IIMulticenter StudyRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Cancer, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers, 7 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
48citing papers in PubMed, 7 pooled it
14.4field-weighted citation impact, top 1% 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

48 citing papers in PubMed, 7 syntheses or guidelines pooled it, 109 citations in OpenAlex.

  1. Pooled it
  2. Targeted therapy for metastatic renal cell carcinoma.The Cochrane database of systematic reviews · 2020
    Pooled it
  3. Immunotherapy for metastatic renal cell carcinoma.The Cochrane database of systematic reviews · 2017
    Pooled it
  4. Pooled it
  5. Pooled it
  6. Pooled it
  7. Pooled it
  8. Trial
  9. Tivozanib versus sorafenib as initial targeted therapy for patients with metastatic renal cell carcinoma: results from a phase III trial.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2013
    Trial
  10. Phase II trial of sequential subcutaneous interleukin-2 plus interferon alpha followed by sorafenib in renal cell carcinoma (RCC).Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2013
    Trial
  11. Trial
  12. Review
  13. Article
  14. Molecular mechanisms of resistance to tyrosine kinase inhibitor in clear cell renal cell carcinoma.International journal of urology : official journal of the Japanese Urological Association · 2022
    Review
  15. Novel Drugs with High Efficacy against Tumor Angiogenesis.International journal of molecular sciences · 2022
    Review
  16. Review
  17. Review
  18. Monitoring cancer cell surface receptor expression during anti-angiogenesis therapy in vivo.Proceedings of SPIE--the International Society for Optical Engineering · 2021
    Article
  19. Review
  20. 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

16 authors at 12 institutions in 4 countries.

Brian RiniThe Cleveland Clinic Taussig Cancer Center, Cleveland, Ohio 44195, USA. rinib2@ccf.org
Cezary Szczylik
Nizar M Tannir
Piotr Koralewski
Piotr Tomczak
Andrzej Deptala
Luc Y Dirix
Mayer Fishman
Rodryg Ramlau
Alain Ravaud
Wojciech Rogowski
Karolyn Kracht
Yu-Nien Sun
Michael B Bass
Markus Puhlmann
Bernard Escudier
Amgen (United States) · USCentre Hospitalier Universitaire de Bordeaux · FRCleveland Clinic · USGZA Ziekenhuizen Campus Sint-Augustinus · BEInstitut Gustave Roussy · FRMedical University of Warsaw · PLMiędzyleski Szpital Specjalistyczny w Warszawie · PLPoznan University of Medical Sciences · PLThe University of Texas MD Anderson Cancer Center · USUniversity Hospital of Lord’s Transfiguration · PLUniversity of South Florida · USWojskowy Instytut Medycyny Lotniczej · PL

Funding

TRANSLATIONAL RESEARCHP30CA076292 · NCI · UNIVERSITY OF SOUTH FLORIDA · PI KENNETH Lynn WRIGHT · 1998 to 2026
$93.5M
NCI NIH HHS P30 CA076292
6 · The paper itself

Abstract

backgroundThis study evaluated the tolerability and antitumor activity of AMG 386, a peptibody (a peptide Fc fusion) that neutralizes the interaction of angiopoietin-1 and angiopoietin-2 with Tie2 (tyrosine kinase with immunoglobulin-like and EGF-like domains 2), plus sorafenib in patients with clear cell metastatic renal cell carcinoma (mRCC) in a randomized controlled study.

methodsPreviously untreated patients with mRCC were randomized 1:1:1 to receive sorafenib 400 mg orally twice daily plus intravenous AMG 386 at 10 mg/kg (arm A) or 3 mg/kg (arm B) or placebo (arm C) once weekly (qw). Patients in arm C could receive open-label AMG 386 at 10 mg/kg qw plus sorafenib following disease progression. The primary endpoint was progression-free survival (PFS).

resultsA total of 152 patients were randomized. Median PFS was 9.0, 8.5, and 9.0 months in arms A, B, and C, respectively (hazard ratio for arms A and B vs arm C, 0.88; 95% confidence interval [CI], 0.60-1.30; P = .523). The objective response rate (95% CI) for arms A, B, and C, respectively, was 38% (25%-53%), 37% (24%-52%), and 25% (14%-40%). Among 30 patients in arm C who had disease progression and subsequently received open-label AMG 386 at 10 mg/kg qw, the objective response rate was 3% (95% CI, 0%-17%). Frequently occurring adverse events (AEs) included diarrhea (arms A/B/C, 70%/67%/56%), palmar-plantar erythrodysesthesia syndrome (52%/47%/54%), alopecia (50%/45%/50%), and hypertension (42%/49%/46%). Fifteen patients had grade 4 AEs (arms A/B/C, n = 3/7/5); 4 had fatal AEs (n = 2/1/1), with 1 (abdominal pain, arm B) considered possibly related to AMG 386.

conclusionsIn patients with mRCC, AMG 386 plus sorafenib was tolerable but did not significantly improve PFS compared with placebo plus sorafenib.

Indexed as

AdultAgedAged, 80 and overAntineoplastic AgentsAntineoplastic Combined Chemotherapy ProtocolsBenzenesulfonatesBiomarkers, TumorCarcinoma, Renal CellDouble-Blind MethodEnzyme-Linked Immunosorbent AssayFemaleFollow-Up StudiesHumansKidney NeoplasmsMaleMiddle AgedAntineoplastic AgentsBenzenesulfonatesBiomarkers, TumorNiacinamidePhenylurea CompoundsPyridinesRecombinant Fusion ProteinsSorafenibtrebananib

Identifiers

PMID22692704
PMCPMC4666535
OpenAlexW2095235698

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.