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

TY - JOUR

T1 - Maintenance durvalumab after first-line chemotherapy in patients with HER2-negative advanced oesophago-gastric adenocarcinoma

T2 - results from the randomised PLATFORM study

AU - Fong, C.

AU - Patel, B.

AU - Peckitt, C.

AU - Bourmpaki, E.

AU - Satchwell, L.

AU - Cromarty, S.

AU - Kidd, S.

AU - von Loga, K.

AU - Uhlik, M.

AU - Begum, R.

AU - Rana, T.

AU - Waddell, T.

AU - Darby, S.

AU - Bradshaw, A.

AU - Roques, T.

AU - Morgan, C.

AU - Rees, C.

AU - Herbertson, R.

AU - Das, P.

AU - Thompson, C.

AU - Hewish, M.

AU - Petty, R.

AU - Thistlethwaite, F.

AU - Rao, S.

AU - Starling, N.

AU - Chau, I.

AU - Cunningham, D.

N1 - Publisher Copyright: © 2024 The Author(s)

PY - 2024/7

Y1 - 2024/7

N2 - 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.

AB - 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.

KW - checkpoint inhibitor

KW - durvalumab

KW - gastric cancer

KW - maintenance therapy

KW - oesophageal adenocarcinoma

UR - https://www.scopus.com/pages/publications/85198049601

U2 - 10.1016/j.esmoop.2024.103622

DO - 10.1016/j.esmoop.2024.103622

M3 - Article

C2 - 39002179

AN - SCOPUS:85198049601

SN - 2059-7029

VL - 9

JO - ESMO open

JF - ESMO open

IS - 7

M1 - 103622

ER -