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Plasma PlGF as a Potential Biomarker in Ramucirumab-Based Second-Line Therapy for Advanced Gastroesophageal
Jurek Hille1,2, Sylvie Lorenzen3, Claudia Pauligk4
1Department of Oncology, Hematology and Bone Marrow Transplantation With Section Pneumology, University Medical Center Hamburg-Eppendorf, Hamburg, 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 HRu = 1.75; p = 0.020; c2d1 HRu = 1.69; p = 0.054). After multivariate adjustment, the association remained directionally consistent; although statistical support was retained only for c2d1 (baseline HRm = 1.41, p = 0.198; c2d1 HRm = 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.
Insights
Elevated placental growth factor (PlGF) during ramucirumab treatment is linked to poorer survival in advanced gastric cancer. This finding suggests PlGF may be a dynamic prognostic marker requiring further validation.
Area of Science:
- Oncology
- Biomarker Research
- Gastrointestinal Cancer
Background:
- Ramucirumab (RAM) is a standard second-line antiangiogenic therapy for advanced gastric and gastroesophageal junction (GEJ) adenocarcinoma.
- Reliable biomarkers to predict treatment response or prognosis are currently lacking for RAM therapy.
Purpose of the Study:
- To explore placental growth factor (PlGF), carbonic anhydrase IX (CAIX), and tryptase as potential biomarkers in patients receiving RAM-based therapy.
- To investigate the association of these biomarkers with progression-free survival (PFS) and overall survival (OS).
Main Methods:
- Plasma samples from 99 patients in the RAMIRIS trial were analyzed at baseline and during treatment.
- PlGF, CAIX, and tryptase levels were quantified using ELISA.
- Associations with PFS and OS were assessed using Cox regression models.
Main Results:
- PlGF levels increased significantly during RAM treatment.
- Elevated baseline and early-treatment PlGF levels were associated with shorter overall survival (OS), particularly after multivariate adjustment for early-treatment levels.
- CAIX and tryptase levels did not show consistent associations with survival outcomes.
Conclusions:
- Elevated PlGF, especially its dynamic increase during therapy, may serve as a prognostic marker for unfavorable outcomes in advanced gastric/GEJ adenocarcinoma treated with ramucirumab.
- These exploratory findings require validation in independent studies to confirm PlGF's role as a predictive or prognostic biomarker.
