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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 adenocarcinomaстатья
Статья опубликована в высокорейтинговом журнале
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Статья опубликована в журнале из списка Web of Science и/или Scopus
Дата последнего поиска статьи во внешних источниках: 4 марта 2022 г.
- Авторы: Sahin1 U., 2, 3, Türeci3, 4, Manikhas5 G., Lordick6 F., Rusyn7 A., Vynnychenko8 I., Dudov9 A., Bazin I., Bondarenko11 I., Melichar12 B., Dhaene13 K., Wiechen14 K., Huber1 C., 3, 4, Maurus15 D., Arozullah16 A., Park16 J.W., Schuler17y M., Al-Batran18* S.E.
- Журнал: Annals of Oncology
- Том: 32
- Номер: 5
- Год издания: 2021
- Издательство: Oxford University Press
- Местоположение издательства: United Kingdom
- Первая страница: 609
- Последняя страница: 619
- DOI: 10.1016/j.annonc.2021.02.005
- Аннотация: Background: Claudin 18.2 (CLDN18.2) is contained within normal gastric mucosa epithelial tight junctions; uponmalignant 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 oesophagealadenocarcinoma patients (aged 18 years) with moderate-to-strong CLDN18.2 expression in 40% tumour cells.Patients received first-line epirubicin oxaliplatin capecitabine (EOX, arm 1, n 84) every 3 weeks (Q3W), orzolbetuximab EOX (loading dose, 800 mg/m2 then 600 mg/m2 Q3W) (arm 2, n 77). Arm 3 (exploratory) wasadded after enrolment initiation (zolbetuximab EOX 1000 mg/m2 Q3W, n 85). The primary endpoint wasprogression-free survival (PFS) and overall survival (OS) was a secondary endpoint.Results: In the overall population, both PFS [hazard ratio (HR) 0.44; 95% confidence interval (CI), 0.29-0.67; P <0.0005] and OS (HR 0.55; 95% CI, 0.39-0.77; P < 0.0005) were significantly improved with zolbetuximab EOX(arm 2) compared with EOX alone (arm 1). This significant PFS benefit was retained in patients with moderate-tostrongCLDN18.2 expression in 70% of tumour cells (HR 0.38; 95% CI, 0.23-0.62; P < 0.0005). Significantimprovement in PFS was also reported in the overall population of arm 3 versus arm 1 (HR 0.58; 95% CI, 0.39-0.85; P 0.0114) but not in high CLDN18.2-expressing patients; no significant improvement in OS was observed ineither population. Most adverse events (AEs) related to zolbetuximab EOX (nausea, vomiting, neutropenia,anaemia) were grade 1-2. Grade 3 AEs showed no substantial increases overall (zolbetuximab EOX versus EOXalone).Conclusions: In advanced gastric/gastro-oesophageal junction and oesophageal adenocarcinoma patients expressingCLDN18.2, adding zolbetuximab to first-line EOX provided longer PFS and OS versus EOX alone. Zolbetuximab EOXwas generally tolerated and AEs were manageable. Zolbetuximab 800/600 mg/m2 is being evaluated in phase IIIstudies based on clinical benefit observed in the overall population and in patients with moderate-to-strongCLDN18.2 expression in 70% of tumour cells.Key words: advanced gastric cancer, advanced gastroesophageal junction adenocarcinoma, advanced oesophagealadenocarcinoma, zolbetuximab, claudin 18.2, epirubicin, oxaliplatin, capecitabine (EOX)
- Добавил в систему: Базин Игорь Сергеевич