Lorlatinib Induces Durable Disease Stabilization in a Pancreatic Cancer Patient with a ROS1 p.L1950F Mutation: Case Report.


Journal

Oncology research and treatment
ISSN: 2296-5262
Titre abrégé: Oncol Res Treat
Pays: Switzerland
ID NLM: 101627692

Informations de publication

Date de publication:
2021
Historique:
received: 10 03 2021
accepted: 04 06 2021
pubmed: 29 7 2021
medline: 16 10 2021
entrez: 28 7 2021
Statut: ppublish

Résumé

The prognosis of pancreatic cancer has improved only modestly in recent years. This is partly due to the lack of development in precision oncology including immune oncology in this entity. Rearrangements of the proto-oncogene tyrosine protein kinase ROS1 gene represent driver alterations found especially in lung cancer. Tyrosine kinase inhibitors (TKI) with activity against ROS1 including lorlatinib substantially improved the outcome of this patient population. Anecdotal evidence reports treatment of pancreatic cancer harboring ROS1 fusions with ROS1 TKI, but data concerning treatment of patients with ROS1 point mutations are lacking. This case describes a pancreatic cancer patient harboring a ROS1 point mutation that occurred without an underlying ROS1 rearrangement and thus not in the resistance situation. The heavily pretreated patient showed a strong decrease of the tumor biomarkers (CA19-9 and CEA) and radiologically a durable stable disease to the targeted treatment with lorlatinib, thereby achieving a progression-free survival of 12 months. Our data are the first to show a clinical benefit from targeted treatment with ROS1 TKI in a cancer patient with a thus far undescribed ROS1 point mutation without a concomitant ROS1 rearrangement. Furthermore, they indicate that ROS1 could be an oncogenic driver in pancreatic cancer. This subgroup could be eligible for targeted treatments, which may contribute to the urgently needed improvement in patient outcome.

Identifiants

pubmed: 34320493
pii: 000517616
doi: 10.1159/000517616
doi:

Substances chimiques

Aminopyridines 0
Lactams 0
MAS1 protein, human 0
Protein Kinase Inhibitors 0
Proto-Oncogene Mas 0
Proto-Oncogene Proteins 0
Pyrazoles 0
Protein-Tyrosine Kinases EC 2.7.10.1
ROS1 protein, human EC 2.7.10.1
lorlatinib OSP71S83EU

Types de publication

Case Reports

Langues

eng

Sous-ensembles de citation

IM

Pagination

495-502

Informations de copyright

© 2021 S. Karger AG, Basel.

Auteurs

Janna-Lisa Velthaus (JL)

Department of Hematology, Oncology and Bone Marrow Transplantation with Section Pneumology, Hubertus Wald Tumorzentrum, University Comprehensive Cancer Center Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany, j.velthaus@uke.de.

Peter Iglauer (P)

Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Ronald Simon (R)

Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Carsten Bokemeyer (C)

Department of Hematology, Oncology and Bone Marrow Transplantation with Section Pneumology, Hubertus Wald Tumorzentrum, University Comprehensive Cancer Center Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Peter Bannas (P)

Department of Diagnostic and Interventional Radiology and Nuclear Medicine, University Medical Center Hamburg Eppendorf, Hamburg, Germany.

Niklas Beumer (N)

Division of Personalized Medical Oncology (A420), German Cancer Research Center (DKFZ), Heidelberg, Germany.
Division of Applied Bioinformatics (B330), German Cancer Research Center (DKFZ), Heidelberg, Germany.
Faculty of Biosciences, Heidelberg University, Heidelberg, Germany.

Charles D Imbusch (CD)

Division of Applied Bioinformatics (B330), German Cancer Research Center (DKFZ), Heidelberg, Germany.

Eray Goekkurt (E)

Department of Hematology, Oncology and Bone Marrow Transplantation with Section Pneumology, Hubertus Wald Tumorzentrum, University Comprehensive Cancer Center Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Hematology-Oncology Practice Hamburg (HOPE), Hamburg, Germany.

Sonja Loges (S)

Department of Hematology, Oncology and Bone Marrow Transplantation with Section Pneumology, Hubertus Wald Tumorzentrum, University Comprehensive Cancer Center Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Division of Personalized Medical Oncology (A420), German Cancer Research Center (DKFZ), Heidelberg, Germany.
Department of Personalized Oncology, University Hospital Mannheim, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.

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Classifications MeSH