From the Department of Cancer Medicine, INSERM Unité 981, Gustave Roussy, Université Paris-Saclay, Villejuif (Y.L.), the Department of Medical Oncology, Institut de Cancérologie du Gard, Centre Hospitalier Universitaire Caremeau, Nîmes (N.H.), and Montpellier University, Montpellier (N.H.) - all in France; the Department of Medical Oncology, National Cancer Center Hospital East, Chiba, Japan (N.M.); the Division of Hematology and Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine (S.H.P.), and Seoul National University Hospital (J.H.K.) - both in Seoul, South Korea; the Section of Radiotherapy and Imaging, Institute of Cancer Research and Royal Marsden NHS Foundation Trust, Sutton, United Kingdom (R.A.H.); Medical Oncology, Levine Cancer Institute, Atrium Health, Charlotte, NC (E.F.B.); the Department of Urology, University Hospital Frankfurt, Goethe University Frankfurt, Frankfurt am Main, Germany (S.B.); the Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan (V.G.); the Department of Medical Oncology, Hospital Universitario Virgen del Rocío, Seville, Spain (B.P.V.); the Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia (B.T.); Janssen Research and Development, Spring House, PA (S.T., Y.K., S.A., N.L.S.); Janssen Research and Development, Beerse, Belgium (K.D.); Janssen Research and Development, Raritan, NJ (S.M.); and the Department of Genitourinary Medical Oncology, University of Texas M.D. Anderson Cancer Center, Houston (A.O.S.-R.).
N Engl J Med. 2023 Nov 23;389(21):1961-1971. doi: 10.1056/NEJMoa2308849. Epub 2023 Oct 21.
Erdafitinib is a pan-fibroblast growth factor receptor (FGFR) inhibitor approved for the treatment of locally advanced or metastatic urothelial carcinoma in adults with susceptible alterations who have progression after platinum-containing chemotherapy. The effects of erdafitinib in patients with -altered metastatic urothelial carcinoma who have progression during or after treatment with checkpoint inhibitors (anti-programmed cell death protein 1 [PD-1] or anti-programmed death ligand 1 [PD-L1] agents) are unclear.
We conducted a global phase 3 trial of erdafitinib as compared with chemotherapy in patients with metastatic urothelial carcinoma with susceptible alterations who had progression after one or two previous treatments that included an anti-PD-1 or anti-PD-L1. Patients were randomly assigned in a 1:1 ratio to receive erdafitinib or the investigator's choice of chemotherapy (docetaxel or vinflunine). The primary end point was overall survival.
A total of 266 patients underwent randomization: 136 to the erdafitinib group and 130 to the chemotherapy group. The median follow-up was 15.9 months. The median overall survival was significantly longer with erdafitinib than with chemotherapy (12.1 months vs. 7.8 months; hazard ratio for death, 0.64; 95% confidence interval [CI], 0.47 to 0.88; P = 0.005). The median progression-free survival was also longer with erdafitinib than with chemotherapy (5.6 months vs. 2.7 months; hazard ratio for progression or death, 0.58; 95% CI, 0.44 to 0.78; P<0.001). The incidence of grade 3 or 4 treatment-related adverse events was similar in the two groups (45.9% in the erdafitinib group and 46.4% in the chemotherapy group). Treatment-related adverse events that led to death were less common with erdafitinib than with chemotherapy (in 0.7% vs. 5.4% of patients).
Erdafitinib therapy resulted in significantly longer overall survival than chemotherapy among patients with metastatic urothelial carcinoma and alterations after previous anti-PD-1 or anti-PD-L1 treatment. (Funded by Janssen Research and Development; THOR ClinicalTrials.gov number, NCT03390504.).
厄达替尼是一种泛成纤维细胞生长因子受体（FGFR）抑制剂，已获批用于治疗铂类化疗后进展的局部晚期或转移性尿路上皮癌成人患者，这些患者存在敏感改变。厄达替尼在接受检查点抑制剂（抗程序性细胞死亡蛋白 1 [PD-1] 或抗程序性死亡配体 1 [PD-L1] 药物）治疗期间或之后进展的转移性尿路上皮癌伴 改变的患者中的疗效尚不清楚。
我们开展了一项全球 3 期临床试验，在铂类化疗后进展的存在敏感改变的转移性尿路上皮癌患者中比较了厄达替尼与化疗的疗效，这些患者在之前的治疗中接受过一种抗 PD-1 或抗 PD-L1 药物治疗。患者按 1:1 的比例随机分组，分别接受厄达替尼或研究者选择的化疗（多西他赛或长春氟宁）治疗。主要终点是总生存期。
共有 266 例患者接受了随机分组：136 例接受厄达替尼治疗，130 例接受化疗。中位随访时间为 15.9 个月。与化疗相比，厄达替尼显著延长了总生存期（12.1 个月 vs. 7.8 个月；死亡风险比，0.64；95%置信区间[CI]，0.47 至 0.88；P=0.005）。与化疗相比，厄达替尼也显著延长了无进展生存期（5.6 个月 vs. 2.7 个月；进展或死亡风险比，0.58；95%CI，0.44 至 0.78；P<0.001）。两组治疗相关不良事件的发生率相似（厄达替尼组为 45.9%，化疗组为 46.4%）。与化疗相比，厄达替尼治疗导致死亡的治疗相关不良事件更少（分别为 0.7%和 5.4%的患者）。
在先前接受过抗 PD-1 或抗 PD-L1 治疗后进展的转移性尿路上皮癌伴 改变的患者中，厄达替尼治疗的总生存期显著长于化疗。（由 Janssen Research and Development 资助；THOR ClinicalTrials.gov 编号，NCT03390504。）
