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

被引：22

作者：

Wainberg, Zev A. ^{[1
]}

Kang, Yoon-Koo ^{[2
]}

Lee, Keun-Wook ^{[3
]}

Qin, Shukui ^{[4
]}

Yamaguchi, Kensei ^{[5
]}

Kim, In-Ho ^{[6
]}

Saeed, Anwaar ^{[7
]}

Oh, Sang Cheul ^{[8
]}

Li, Jin ^{[9
]}

Turk, Haci Mehmet ^{[10
]}

Teixeira, Alexandra ^{[11
]}

Hitre, Erika ^{[12
]}

Udrea, Adrian A. ^{[13
]}

Cardellino, Giovanni Gerardo ^{[14
]}

Sanchez, Raquel Guardeno ^{[15
]}

Zahlten-Kuemeli, Anita ^{[16
]}

Taylor, Kate ^{[17
]}

Enzinger, Peter C. ^{[18
]}

机构：

[1] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Hematol Oncol,Med Ctr, 2825 Santa Monica Blvd,Suite 200, Los Angeles, CA 90404 USA

[2] Univ Ulsan, Asan Med Ctr, Coll Med, Seoul, South Korea

[3] Seoul Natl Univ, Bundang Hosp, Dept Pathol, Coll Med, Seongnam, South Korea

[4] China Pharmaceut Univ, Nanjing Tianyinshan Hosp, Affiliated Hosp 1, Nanjing, Peoples R China

[5] Canc Inst Hosp JFCR, Gastroenterol Chemotherapy Dept, Tokyo, Japan

[6] Catholic Univ Korea, Seoul St Marys Hosp, Dept Oncol, Seoul, South Korea

[7] Univ Pittsburgh, UPMC Hillman Canc Ctr, Pittsburgh, PA USA

[8] Korea Univ, Guro Hosp, Dept Internal Med, Seoul, South Korea

[9] Tongji Univ, Sch Med, Shanghai East Hosp, Dept Oncol, Shanghai, Peoples R China

[10] Bezmialem Vakif Univ, Dept Med Oncol, Istanbul, Turkiye

[11] Hosp Senhora Oliveira, Gastroenterol Div, Guimaraes, Portugal

[12] Natl Inst Oncol, Dept Med Oncol & Clin Pharmacol B, Budapest, Hungary

[13] Medisprof Canc Ctr, Med Oncol, Cluj Napoca, Romania

[14] Azienda Sanit Univ Friuli Cent, Dept Cardiol, Udine, Italy

[15] Catalan Inst Oncol, Dept Med Oncol, Girona, Spain

[16] Amgen Inc, Thousand Oaks, CA USA

[17] Amgen Inc, Uxbridge, England

[18] Dana Farber Canc Inst, Dept Med, Boston, MA USA

来源：

GASTRIC CANCER | 2024年 / 27卷 / 03期

关键词：

Bemarituzumab; FGFR2b; Gastric cancer; mFOLFOX6; Targeted therapy;

D O I：

10.1007/s10120-024-01466-w

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

BackgroundWe 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).MethodsPatients 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.ResultsIn 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.ConclusionsIn 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 registrationNCT03694522.

引用

页码：558 / 570

页数：13

共 25 条

[1] FGFR2 in gastric cancer: protein overexpression predicts gene amplification and high H-index predicts poor survival [J].