Maintenance durvalumab after first-line chemotherapy in patients with HER2-negative advanced oesophago-gastric adenocarcinoma: results from the randomised PLATFORM study

C. Fong, B. Patel, C. Peckitt, E. Bourmpaki, L. Satchwell, S. Cromarty, S. Kidd, K. von Loga, M. Uhlik, R. Begum, T. Rana, T. Waddell, S. Darby, A. Bradshaw, T. Roques, C. Morgan, C. Rees, R. Herbertson, P. Das, C. ThompsonM. Hewish, R. Petty, F. Thistlethwaite, S. Rao, N. Starling, I. Chau, D. Cunningham (Lead / Corresponding author)

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Abstract

Background 

PLAnning Treatment For Oesophago-gastric Cancer: a Randomised Maintenance Therapy Trial (PLATFORM) is an adaptive phase II study assessing the role of maintenance therapies in advanced oesophago-gastric (OG) adenocarcinoma. We evaluated the role of the anti-programmed death-ligand 1 (PD-L1) inhibitor durvalumab in these patients. 

Patients and methods 

Patients with human epidermal growth factor receptor 2-negative locally advanced or metastatic OG adenocarcinoma with disease control or response to 18 weeks of platinum-based first-line chemotherapy were randomised to active surveillance or maintenance durvalumab. The primary endpoint was progression-free survival (PFS). Safety was assessed in all patients who had commenced surveillance visits or received at least one dose of durvalumab. Exploratory survival analyses according to PD-L1 Combined Positive Score (CPS) and immune (biomarker-positive) or angiogenesis dominant (biomarker-negative) tumour microenvironment (TME) phenotypes were conducted. 


Results 

Between March 2015 and April 2020, 205 patients were randomised to surveillance (n = 100) and durvalumab (n = 105). No significant differences were seen in PFS [hazard ratio (HR) 0.84, P = 0.13] and overall survival (OS; HR 0.98, P = 0.45) between surveillance and durvalumab. Five patients randomised to durvalumab demonstrated incremental radiological responses compared with none with surveillance. Treatment-related adverse events occurred in 77 (76.2%) durvalumab-assigned patients. A favourable effect in OS with durvalumab over surveillance in CPS ≥5 and immune biomarker-positive patients was observed compared with CPS <5 and biomarker-negative subgroups, respectively: CPS ≥5 versus <5: HR 0.63, 95% confidence interval (CI) 0.32-1.22 versus HR 0.93, 95% CI 0.44-1.96; biomarker-positive versus negative: HR 0.60, 95% CI 0.29-1.23 versus HR 0.84, 95% CI 0.42-1.65. 

Conclusion 

Maintenance durvalumab does not improve PFS in patients with OG adenocarcinoma who respond to first-line chemotherapy but induced incremental radiological responses in a subset of patients. TME characterisation could refine patient selection for anti-PD-L1 therapy above PD-L1 CPS alone.

Original languageEnglish
Article number103622
Number of pages10
JournalESMO open
Volume9
Issue number7
Early online date13 Jul 2024
DOIs
Publication statusPublished - Jul 2024

Keywords

  • checkpoint inhibitor
  • durvalumab
  • gastric cancer
  • maintenance therapy
  • oesophageal adenocarcinoma

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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