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Title | FAST: a randomised phase II study of zolbetuximab (IMAB362) plus EOX versus EOX alone for first-line treatment of advanced CLDN18.2-positive gastric and gastro-oesophageal adenocarcinoma |
Authors |
Sahin, U.
Türeci, Ö. Manikhas, G. Lordick, F. Rusyn, A. Vynnychenko, Ihor Oleksandrovych ![]() Dudov, A. Bazin, I. Bondarenko, I. Melichar, B. Dhaene, K. Wiechen, K. Huber, C. Maurus, D. Arozullah, A. Park, J. W. Schuler, M. Al-Batran, S.-E. |
ORCID |
http://orcid.org/0000-0002-2339-6509 |
Keywords |
advanced gastric cancer advanced gastroesophageal junction adenocarcinoma advanced oesophageal adenocarcinoma zolbetuximab claudin 18.2 epirubicin oxaliplatin capecitabine (EOX) |
Type | Article |
Date of Issue | 2021 |
URI | https://essuir.sumdu.edu.ua/handle/123456789/98486 |
Publisher | European Society For Medical Oncology |
License | Creative Commons Attribution 4.0 International License |
Citation | FAST: a randomised phase II study of zolbetuximab (IMAB362) plus EOX versus EOX alone for first-line treatment of advanced CLDN18.2-positive gastric and gastro-oesophageal adenocarcinoma / U. Sahin et al. // Annals of Oncology/ 2021. Vol. 32. Is. 5. P. 609-619. https://doi.org/10.1016/j.annonc.2021.02.005. |
Abstract |
Background: Claudin 18.2 (CLDN18.2) is contained within normal gastric mucosa epithelial tight junctions; upon
malignant transformation, CLDN18.2 epitopes become exposed. Zolbetuximab, a chimeric monoclonal antibody,
mediates specific killing of CLDN18.2-positive cells through immune effector mechanisms.
Patients and methods: The FAST study enrolled advanced gastric/gastro-oesophageal junction and oesophageal
adenocarcinoma patients (aged 18 years) with moderate-to-strong CLDN18.2 expression in 40% tumour cells.
Patients received first-line epirubicin þ oxaliplatin þ capecitabine (EOX, arm 1, n ¼ 84) every 3 weeks (Q3W), or
zolbetuximab þ EOX (loading dose, 800 mg/m2 then 600 mg/m2 Q3W) (arm 2, n ¼ 77). Arm 3 (exploratory) was
added after enrolment initiation (zolbetuximab þ EOX 1000 mg/m2 Q3W, n ¼ 85). The primary endpoint was
progression-free survival (PFS) and overall survival (OS) was a secondary endpoint.
Results: In the overall population, both PFS [hazard ratio (HR) ¼ 0.44; 95% confidence interval (CI), 0.29-0.67; P <
0.0005] and OS (HR ¼ 0.55; 95% CI, 0.39-0.77; P < 0.0005) were significantly improved with zolbetuximab þ EOX
(arm 2) compared with EOX alone (arm 1). This significant PFS benefit was retained in patients with moderate-tostrong CLDN18.2 expression in 70% of tumour cells (HR ¼ 0.38; 95% CI, 0.23-0.62; P < 0.0005). Significant
improvement in PFS was also reported in the overall population of arm 3 versus arm 1 (HR ¼ 0.58; 95% CI, 0.39-
0.85; P ¼ 0.0114) but not in high CLDN18.2-expressing patients; no significant improvement in OS was observed in
either population. Most adverse events (AEs) related to zolbetuximab þ EOX (nausea, vomiting, neutropenia,
anaemia) were grade 1-2. Grade 3 AEs showed no substantial increases overall (zolbetuximab þ EOX versus EOX
alone).
Conclusions: In advanced gastric/gastro-oesophageal junction and oesophageal adenocarcinoma patients expressing
CLDN18.2, adding zolbetuximab to first-line EOX provided longer PFS and OS versus EOX alone. Zolbetuximab þ EOX
was generally tolerated and AEs were manageable. Zolbetuximab 800/600 mg/m2 is being evaluated in phase III
studies based on clinical benefit observed in the overall population and in patients with moderate-to-strong
CLDN18.2 expression in 70% of tumour cells. |
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