# Bevacizumab and Tocotrienol in Recurrent Platinum-Resistant Ovarian Cancer, and the Role of HOXA9 as a Prognostic Biomarker

**Authors:** Elisabeth Emanuel Graae, Louise Faaborg, Rikke Fredslund Andersen, Lars Ulrik Fokdal, Caroline Brenner Thomsen

PMC · DOI: 10.3390/diseases14030104 · 2026-03-12

## TL;DR

This study explores the use of bevacizumab and tocotrienol in treating platinum-resistant ovarian cancer and investigates meth-HOXA9 as a potential biomarker for prognosis.

## Contribution

The study evaluates meth-HOXA9 as a prognostic biomarker in platinum-resistant ovarian cancer treated with bevacizumab and tocotrienol.

## Key findings

- The overall survival in the cohort was 7.5 months with a progression-free survival of 4 months.
- Baseline meth-HOXA9 levels did not show a statistically significant difference in overall survival.
- A few patients showed an extraordinary response in terms of progression-free survival.

## Abstract

Background/Objectives: Platinum resistant ovarian cancer represents a treatment challenge due to lack of efficient treatments and the absence of prognostic biomarkers. The circulating tumor DNA (ctDNA), methylated homebox A9 (meth-HOXA9), has been suggested as a biomarker for ovarian cancer, and might have a clinical impact in terms of predicting progression and supporting clinical decision making. Hence, this study investigated the prognostic value of meth-HOXA9 in platinum resistant recurrent ovarian cancer (PR-ROC) treated with bevacizumab and tocotrienol. Methods: Twenty patients with platin-resistant recurrent ovarian cancer were prospectively enrolled in this non-randomized phase II study. The treatment consisted of bevacizumab (Avastin) 10 mg/kg intravenously every three weeks and tocotrienol (Traptol) capsules 300 mg orally three times daily as a continuous treatment. The Level of meth-HOXA9 was measured at baseline and every three weeks. Results: The overall survival (OS) in the cohort was 7.5 months (95% CI 3.0–10.0), and the progression free survival was 4 months (95% CI 1.4–6.6). Comparing meth-HOXA9 ctDNA levels at baseline, there was no statistic significant difference in OS (p = 0.23). Conclusions: Treatment was well tolerated in this heavily pretreated cohort of PR-ROC patients with expected poor prognostic outcomes, with a few individuals showing extraordinary response in terms of progression free survival. The study was not powered to reproduce evidence of potential of meth-HOXA9 as a prognostic biomarker in PR-ROC.

## Linked entities

- **Genes:** HOXA9 (homeobox A9) [NCBI Gene 3205]
- **Chemicals:** tocotrienol (PubChem CID 92161)
- **Diseases:** ovarian cancer (MONDO:0005140)

## Full-text entities

- **Genes:** HOXA9 (homeobox A9) [NCBI Gene 3205] {aka ABD-B, HOX1, HOX1.7, HOX1G}, PGR (progesterone receptor) [NCBI Gene 5241] {aka NR3C3, PR}, MUC16 (mucin 16, cell surface associated) [NCBI Gene 94025] {aka CA125}, ALB (albumin) [NCBI Gene 213] {aka FDAHT, HSA, PRO0883, PRO0903, PRO1341}, VEGFA (vascular endothelial growth factor A) [NCBI Gene 7422] {aka L-VEGF, MVCD1, VEGF, VPF}, HOXA@ (homeobox A cluster) [NCBI Gene 3197] {aka HOX1@}
- **Diseases:** bleeding (MESH:D006470), serous carcinoma (MESH:D018297), injury to (MESH:D014947), epistaxis (MESH:D004844), PR (MESH:D008151), proteinuria (MESH:D011507), anemia (MESH:D000740), thromboembolism (MESH:D013923), hypertension (MESH:D006973), Toxicity (MESH:D064420), cardiovascular disease (MESH:D002318), thrombosis (MESH:D013927), basal cell carcinoma (MESH:D002280), hyperkalemia (MESH:D006947), epithelial ovarian cancer (MESH:D000077216), Solid Tumours (MESH:D009369), allergies (MESH:D004342), death (MESH:D003643), cardiac disease (MESH:D006331), OC (MESH:D010051), squamous cell carcinoma of the skin (MESH:D002294), diabetes (MESH:D003920), cerebral vascular attack (MESH:D002532), gastrointestinal perforation (MESH:D005767)
- **Chemicals:** Meth (-), Tocotrienol (MESH:D024508), E-vitamin (MESH:D014810), Platinum (MESH:D010984), PLD (MESH:C506643), topotecan (MESH:D019772), EDTA (MESH:D004492), Avastin (MESH:D000068258), paclitaxel (MESH:D017239), water (MESH:D014867)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Figures

2 figures with captions in the complete paper: https://tomesphere.com/paper/PMC13024877/full.md

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Source: https://tomesphere.com/paper/PMC13024877