Elucidating predictors of treatment response in oesophago-gastric cancers
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Embargo End Date
2026-03-01
ICR Authors
Authors
Fong, C
Document Type
Thesis or Dissertation
Date
2025-09-01
Date Accepted
Abstract
Cytotoxic chemotherapy has underpinned the treatment landscape of advanced oesophago-gastric adenocarcinoma (OGA) for decades. However, the median overall survival following first-line platinum-fluoropyrimidine chemotherapy in human epidermal growth factor (HER2)-negative disease remains limited at less than 12 months. This highlights a need for innovative therapeutic approaches, using both novel drugs and unexploited treatment settings.
The PLATFORM study is a multi-centre, randomised, adaptive phase II study assessing the efficacy of maintenance therapies in advanced OGA patients with radiologically proven disease control or response following 18 weeks of first-line platinum-fluoropyrimidine chemotherapy. To evaluate the impact of maintenance therapies on progression-free survival (PFS), the study design allows simultaneous recruitment into multiple interventional arms which are independently compared against active surveillance. Results from the PLATFORM study showed that maintenance durvalumab did not prolong PFS compared to active surveillance (median PFS: 3.0 versus 3.2 months respectively, hazard ratio 0.84; 95% confidence interval 0.62 – 1.14; one-sided p value 0.13).
To investigate the effect of predictive biomarkers on identifying patients who may benefit from maintenance durvalumab, exploratory analyses of programmed death ligand-1 Combined Positive Score (CPS) expression were conducted. Maintenance durvalumab did not improve median PFS or overall survival (OS) in patient with CPS ≥5 when compared to those with CPS <5 tumours. Further evaluation using a novel tumour microenvironment (TME) RNA-based panel which classifies the TME along immune and angiogenic axes showed that patient treated with durvalumab with a high immune score (biomarker-positive) had higher 12-month PGS and 24- month OS rates compared to those with a low immune score (biomarker-negative), Within the CPS ≥5 population assigned to durvalumab, a numerical improvement in 12- and 24-months OS rates were also seen in biomarker-positive patients when compared to those who were biomarker-negative.
Signed
Citation
2025
DOI
Source Title
Publisher
Institute of Cancer Research (University Of London)
ISSN
eISSN
Collections
Research Team
Transl Oncogenomics