Bemarituzumab as first-line treatment for locally advanced or metastatic gastric/gastroesophageal junction adenocarcinoma: final analysis of the randomized phase 2 FIGHT trial.

Autor: Wainberg ZA; Division of Hematology-Oncology, Department of Medicine, University of California Los Angeles Medical Center, David Geffen School of Medicine, 2825 Santa Monica Blvd., Suite 200, Santa Monica, Los Angeles, CA, 90404-2429, USA. ZWainberg@mednet.ucla.edu., Kang YK; Asan Medical Centre, University of Ulsan College of Medicine, Seoul, South Korea., Lee KW; Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea., Qin S; Nanjing Tianyinshan Hospital, The 1st Affiliated Hospital of China Pharmaceutical University, Nanjing, China., Yamaguchi K; Gastroenterological Chemotherapy Department, The Cancer Institute Hospital of JFCR, Tokyo, Japan., Kim IH; Department of Oncology, The Catholic University of Korea, Seoul St Mary's Hospital, Seoul, South Korea., Saeed A; UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA, USA., Oh SC; Department of Internal Medicine, Korea University Guro Hospital, Seoul, South Korea., Li J; Department of Oncology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China., Turk HM; Department of Medical Oncology, Bezmialem Vakif University, Istanbul, Turkey., Teixeira A; Gastroenterology Division, Hospital da Senhora da Oliveira, Guimarães, Portugal., Hitre E; Department of Medical Oncology and Clinical Pharmacology 'B', National Institute of Oncology, Budapest, Hungary., Udrea AA; Medical Oncology, Medisprof Cancer Center, Cluj-Napoca, Romania., Cardellino GG; Department of Oncology, Azienda Sanitaria Universitaria Friuli Centrale, Udine, Italy., Sanchez RG; Department of Medical Oncology, Catalan Institute of Oncology, Girona, Spain., Zahlten-Kümeli A; Amgen Inc, Thousand Oaks, CA, USA., Taylor K; Amgen Inc, Uxbridge, UK., Enzinger PC; Department of Medicine, Dana-Farber Cancer Institute, Boston, MA, USA.
Jazyk: angličtina
Zdroj: Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association [Gastric Cancer] 2024 May; Vol. 27 (3), pp. 558-570. Date of Electronic Publication: 2024 Feb 03.
DOI: 10.1007/s10120-024-01466-w
Abstrakt: Background: We report the final results of the randomized phase 2 FIGHT trial that evaluated bemarituzumab, a humanized monoclonal antibody selective for fibroblast growth factor receptor 2b (FGFR2b), plus mFOLFOX6 in patients with FGFR2b-positive (2 + /3 + membranous staining by immunohistochemistry), HER-2-negative gastric or gastroesophageal junction cancer (GC).
Methods: Patients received bemarituzumab (15 mg/kg) or placebo once every 2 weeks with an additional bemarituzumab (7.5 mg/kg) or placebo dose on cycle 1 day 8. All patients received mFOLFOX6. The primary endpoint was investigator-assessed progression-free survival (PFS). Secondary endpoints included overall survival (OS), objective response rate, and safety. Efficacy was evaluated after a minimum follow-up of 24 months.
Results: In the bemarituzumab-mFOLFOX6 (N = 77) and placebo-mFOLFOX6 (N = 78) arms, respectively, 59.7% and 66.7% of patients were FGFR2b-positive in ≥ 10% of tumor cells. The median PFS (95% confidence interval [CI]) was 9.5 months (7.3-13.7) with bemarituzumab-mFOLFOX6 and 7.4 months (5.7-8.4) with placebo-mFOLFOX6 (hazard ratio [HR], 0.72; 95% CI 0.49-1.08); median OS (95% CI) was 19.2 (13.6-24.2) and 13.5 (9.3-15.9) months, respectively (HR 0.77; 95% CI 0.52-1.14). Observed efficacy in FGFR2b-positive GC in ≥ 10% of tumor cells was: PFS: HR 0.43 (95% CI 0.26-0.73); OS: HR 0.52 (95% CI 0.31-0.85). No new safety findings were reported.
Conclusions: In FGFR2b-positive advanced GC, the combination of bemarituzumab-mFOLFOX6 led to numerically longer median PFS and OS compared with mFOLFOX6 alone. Efficacy was more pronounced with FGFR2b overexpression in ≥ 10% of tumor cells. Confirmatory phase 3 trials are ongoing (NCT05052801, NCT05111626).
Clinical Trial Registration: NCT03694522.
(© 2024. The Author(s).)
Databáze: MEDLINE
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