Evidence map›Paper›PMID 32436621›Full record

ArticleCancer medicine2020

Sorafenib and everolimus in patients with advanced solid tumors and KRAS-mutated NSCLC: A phase I trial with early pharmacodynamic FDG-PET assessment.

Lucia Nogova, Christian Mattonet, Matthias Scheffler, Max Taubert, Masyar Gardizi, Martin L Sos, Sebastian Michels, Rieke N Fischer, Meike Limburg, Diana S Y Abdulla and 21 more

Abstract readClinical Trial, Phase I
PubMed Full text at PMC Publisher
In one paragraph

Article in Cancer medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
–field-weighted citation impact
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

13 citing papers in PubMed.

  1. Review
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  7. c-MYC-mediated TRIB3/P62Acta pharmaceutica Sinica. B · 2022
    Article
  8. Review
  9. Programmed cell death, redox imbalance, and cancer therapeutics.Apoptosis : an international journal on programmed cell death · 2021
    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

31 authors.

Lucia NogovaDepartment I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, Lung Cancer Group, University of Cologne, Cologne, Germany.ORCID 0000-0002-4502-1812
Christian MattonetDepartment I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, Lung Cancer Group, University of Cologne, Cologne, Germany.
Matthias SchefflerDepartment I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, Lung Cancer Group, University of Cologne, Cologne, Germany.ORCID 0000-0002-9031-1368
Max TaubertFaculty of Medicine and University Hospital Cologne, Center for Pharmacology, Department I of Pharmacology, University of Cologne, Cologne, Germany.
Masyar GardiziDepartment I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, Lung Cancer Group, University of Cologne, Cologne, Germany.
Martin L SosDepartment I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, Lung Cancer Group, University of Cologne, Cologne, Germany.ORCID 0000-0002-2868-100X
Sebastian MichelsDepartment I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, Lung Cancer Group, University of Cologne, Cologne, Germany.
Rieke N FischerDepartment I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, Lung Cancer Group, University of Cologne, Cologne, Germany.
Meike LimburgDepartment I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, Lung Cancer Group, University of Cologne, Cologne, Germany.
Diana S Y AbdullaDepartment I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, Lung Cancer Group, University of Cologne, Cologne, Germany.
Thorsten PersigehlFaculty of Medicine and University Hospital Cologne, Institute for Diagnostics und Intervention Radiology, University of Cologne, Cologne, Germany.
Carsten KobeFaculty of Medicine and University Hospital Cologne, Department for Nuclear Medicine, University of Cologne, Cologne, Germany.
Sabine Merkelbach-BruseFaculty of Medicine and University Hospital Cologne, Institute for Pathology, University of Cologne, Cologne, Germany.
Jeremy FranklinFaculty of Medicine, Institute for Medical Statistics and Bioinformatics, University of Cologne, Cologne, Germany.
Heiko BackesMax Planck Institute for Metabolism Research, Cologne, Germany.
Roland SchnellPraxis for Medical Oncology and Haematology (PIOH), Frechen, Germany.
Dirk BehringerHeamatology and Oncology, Augusta Hospital, Bochum, Germany.
Britta KaminskyBethanien Hospital, Solingen, Germany.
Martina EichstaedtMedical Oncology and Haematology, St. Marien Hospital, Düren, Germany.
Christoph StelzerInstitute for Biomedical and Pharmaceutical Research (IBMP), Nürnberg, Germany.
Martina KinzigInstitute for Biomedical and Pharmaceutical Research (IBMP), Nürnberg, Germany.
Fritz SörgelInstitute for Biomedical and Pharmaceutical Research (IBMP), Nürnberg, Germany.
Yingying TianFaculty of Medicine and University Hospital Cologne, Center for Pharmacology, Department I of Pharmacology, University of Cologne, Cologne, Germany.
Lisa JungeFaculty of Medicine and University Hospital Cologne, Center for Pharmacology, Department I of Pharmacology, University of Cologne, Cologne, Germany.
Ahmed A SuleimanFaculty of Medicine and University Hospital Cologne, Center for Pharmacology, Department I of Pharmacology, University of Cologne, Cologne, Germany.
Sebastian FrechenFaculty of Medicine and University Hospital Cologne, Center for Pharmacology, Department I of Pharmacology, University of Cologne, Cologne, Germany.
Dennis RokittaFaculty of Medicine and University Hospital Cologne, Center for Pharmacology, Department I of Pharmacology, University of Cologne, Cologne, Germany.
Dongsheng OuyangDepartment of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, China.
Uwe FuhrFaculty of Medicine and University Hospital Cologne, Center for Pharmacology, Department I of Pharmacology, University of Cologne, Cologne, Germany.
Reinhard BuettnerFaculty of Medicine and University Hospital Cologne, Institute for Pathology, University of Cologne, Cologne, Germany.
Jürgen WolfDepartment I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, Lung Cancer Group, University of Cologne, Cologne, Germany.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundTreatment of patients with solid tumors and KRAS mutations remains disappointing. One option is the combined inhibition of pathways involved in RAF-MEK-ERK and PI3K-AKT-mTOR.

methodsPatients with relapsed solid tumors were treated with escalating doses of everolimus (E) 2.5-10.0 mg/d in a 14-day run-in phase followed by combination therapy with sorafenib (S) 800 mg/d from day 15. KRAS mutational status was assessed retrospectively in the escalation phase. Extension phase included KRAS-mutated non-small-cell lung cancer (NSCLC) only. Pharmacokinetic analyses were accompanied by pharmacodynamics assessment of E by FDG-PET. Efficacy was assessed by CT scans every 6 weeks of combination.

resultsOf 31 evaluable patients, 15 had KRAS mutation, 4 patients were negative for KRAS mutation, and the KRAS status remained unknown in 12 patients. Dose-limiting toxicity (DLT) was not reached. The maximum tolerated dose (MTD) was defined as 7.5 mg/d E + 800 mg/d S due to toxicities at previous dose level (10 mg/d E + 800 mg/d S) including leucopenia/thrombopenia III° and pneumonia III° occurring after the DLT interval. The metabolic response rate in FDG-PET was 17% on day 5 and 20% on day 14. No patient reached partial response in CT scan. Median progression free survival (PFS) and overall survival (OS) were 3.25 and 5.85 months, respectively.

conclusionsTreatment of patients with relapsed solid tumors with 7.5 mg/d E and 800 mg/d S is safe and feasible. Early metabolic response in FDG-PET was not confirmed in CT scan several weeks later. The combination of S and E is obviously not sufficient to induce durable responses in patients with KRAS-mutant solid tumors.

Indexed as

AdultAgedAntineoplastic Combined Chemotherapy ProtocolsCarcinoma, Non-Small-Cell LungEverolimusFemaleFluorodeoxyglucose F18HumansLung NeoplasmsMaleMiddle AgedPositron-Emission TomographyProto-Oncogene Proteins p21(ras)SorafenibEverolimusFluorodeoxyglucose F18Proto-Oncogene Proteins p21(ras)SorafenibFDG-PETKRAS mutationnon-small-cell lung cancerpharmacodynamicspharmacokineticsPhase-I trialsolid tumors

Identifiers

PMID32436621
PMCPMC7367645

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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.