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Publications

Journal Article Ahead of print

PubMed: 42266015 DOI: 10.1002/ijc.70567

Plasma PlGF as a Potential Biomarker in Ramucirumab-Based Second-Line Therapy for Advanced Gastroesophageal Adenocarcinoma: Exploratory Biomarker Analysis from the Phase II Part of the RAMIRIS Trial.

Int J Cancer

Authors: Jurek Hille, Sylvie Lorenzen, Claudia Pauligk, Victoria Gensch, Peter Thuss-Patience, Eray Goekkurt, Thomas Ettrich, Florian Lordick, Carsten Bokemeyer, Christian Müller, Peter Reichardt, Martin Sökler, Daniel Pink, Stefan Probst, Thorsten O Goetze, Salah E Al-Batran, Sonja Loges, Melanie Janning

Affiliations

  • Department of Oncology, Hematology and Bone Marrow Transplantation With Section Pneumology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. University Cancer Center Hamburg (UCCH), University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
  • Department of Medicine III, TUM University Hospital, Technical University of Munich, Munich, Germany.
  • The Frankfurt Institute for Clinical Cancer Research IKF GmbH, Frankfurt/Main, Germany.
  • DKFZ-Hector Cancer Institute at the University Medical Center Mannheim, Mannheim, Germany.
  • Division of Personalized Medical Oncology (A420), German Cancer Research Center (DKFZ), & Deutsches Zentrum für Lungenforschung (DZL), Heidelberg, Germany.
  • Department of Personalized Oncology, University Hospital Mannheim, Medical Faculty Mannheim University of Heidelberg, Mannheim, Germany.
  • Department of Hematology, Oncology and Cancer Immunology, Charité-University Medicine Berlin, Berlin, Germany.
  • University Cancer Center Hamburg (UCCH), University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
  • Hematology-Oncology Practice Eppendorf (HOPE), Hamburg, Germany.
  • Department of Internal Medicine I, Ulm University Medical Center, Ulm, Germany.
  • Department of Oncology, Gastroenterology, Hepatology, and Pulmonology, University Cancer Center Leipzig (UCCL), Leipzig University Medical Center, Leipzig, Germany.
  • Department of Oncology, Hematology and Bone Marrow Transplantation With Section Pneumology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
  • Department of Medical Oncology, Evang. Kliniken Essen-Mitte, Essen, Germany.
  • Sarcoma Center Berlin-Brandenburg, Helios Klinikum Berlin-Buch, Berlin, Germany.
  • Oncology Spital Thun, Thun, Switzerland.
  • Second Department of Internal Medicine, University Hospital Tübingen, Tübingen, Germany.
  • Department of Oncology and Palliative Care, Helios Klinikum Bad Saarow, Bad Saarow, Germany.
  • Department of Internal Medicine C, University Hospital Greifswald, Greifswald, Germany.
  • Department of Hematology, Oncology and Palliative Medicine, Community Hospital Bielefeld, Bielefeld, Germany.
  • Krankenhaus Nordwest, University Cancer Center Frankfurt, Frankfurt, Germany.
  • Liquid Biopsy and Single Cell Analysis Group, Division of Personalized Medical Oncology (A420), German Cancer Research Center (DKFZ) & Deutsches Zentrum für Lungenforschung (DZL), Heidelberg, Germany.

Abstract

Antiangiogenic treatment with ramucirumab (RAM) is a standard second-line option in advanced gastric and gastroesophageal junction (GEJ) adenocarcinoma. However, reliable biomarkers are lacking. The phase II RAMIRIS trial compared RAM plus paclitaxel with RAM plus FOLFIRI (5-fluororuracil, leucovorin and irinotecan) in this setting. We present the exploratory biomarker analysis evaluating placental growth factor (PlGF), carbonic anhydrase IX (CAIX), and tryptase. Plasma samples from 99 patients enrolled in RAMIRIS were collected at predefined timepoints (baseline, Cycle 2 Day 1, and Cycle 4 Day 1). PlGF, CAIX, and tryptase were quantified by ELISA. Associations with progression-free survival (PFS) and overall survival (OS) were analyzed using dichotomized biomarker levels and Cox regression models. PlGF levels increased substantially under treatment, whereas CAIX showed a transient rise, followed by a slight decline, and tryptase remained stable. Elevated PlGF levels at baseline and early-treatment (c2d1) were associated with shorter OS in univariate analysis (baseline HR u = 1.75; p = 0.020; c2d1 HR u = 1.69; p = 0.054). After multivariate adjustment, the association remained directionally consistent; although statistical support was retained only for c2d1 (baseline HR m = 1.41, p = 0.198; c2d1 HR m = 1.85, p = 0.030). CAIX and tryptase showed no consistent associations with survival. Elevated PlGF-particularly its early increase during RAM-based therapy-was associated with shortened survival and may represent a dynamic marker of unfavorable prognosis in advanced gastric/GEJ adenocarcinoma. Given the exploratory nature of this analysis, these findings should be considered hypothesis-generating and require validation in independent biomarker-driven studies.

MeSH

Neoplasms, Adenocarcinoma, Biomarkers, Tryptases, Therapeutics, Stomach Neoplasms, Plasma