Department of Medical Oncology, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan.
Department of Medical Oncology, Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-8470, Japan.
Int J Clin Oncol. 2024 Oct;29(10):1516-1527. doi: 10.1007/s10147-024-02583-3. Epub 2024 Jul 17.
In the THOR trial (NCT03390504) Cohort 1, erdafitinib demonstrated significantly prolonged overall survival (OS) (median 12.1 versus 7.8 months) and reduced risk of death by 36% (hazard ratio 0.64, P = 0.005) compared with chemotherapy in metastatic urothelial carcinoma (mUC) patients with FGFR alterations who progressed after ≥ 1 prior treatments, including anti-PD-(L)1. There have been no reports of the Japanese subgroup results yet.
THOR Cohort 1 randomized patients to erdafitinib once daily or docetaxel/vinflunine once every 3 weeks. Primary endpoint was OS. Secondary endpoints included progression-free survival (PFS) and objective response rate (ORR). No specific statistical power was set for this Japanese subgroup analysis.
Of 266 patients randomized, 27 (14 erdafitinib; 13 chemotherapy) were Japanese. Baseline characteristics were generally similar between treatments and to the overall population, except for more males, lower body weight, and more upper tract primary tumors among Japanese patients. Compared with chemotherapy, erdafitinib showed improved OS (median 25.4 versus 12.4 months), PFS (median 8.4 versus 2.9 months) and ORR (57.1% versus 15.4%). Any grade treatment-related adverse events (AEs) occurred in all patients from both arms but Grade 3/4 AEs and AEs leading to discontinuation were lower in the erdafitinib arm. No new safety signals were observed in the Japanese subgroup.
In the Japanese subgroup, erdafitinib showed improved survival and response compared to chemotherapy, with no new safety concerns. These results support erdafitinib as a treatment option for Japanese mUC patients with FGFR alterations, and early FGFR testing after diagnosis of mUC should be considered.
在 THOR 试验（NCT03390504）队列 1 中，与化疗相比，厄达替尼显著延长了转移性尿路上皮癌（mUC）患者的总生存期（OS）（中位 12.1 个月 vs 7.8 个月），降低了 36%的死亡风险（风险比 0.64，P=0.005），这些患者在接受包括抗 PD-（L）1 在内的至少 1 种治疗后进展，并且存在 FGFR 改变。目前尚未有关于日本亚组结果的报道。
THOR 队列 1 随机分配患者接受厄达替尼每日一次或多西他赛/vinflunine 每 3 周一次。主要终点为 OS。次要终点包括无进展生存期（PFS）和客观缓解率（ORR）。未为本次日本亚组分析设定特定的统计效力。
在 266 名随机患者中，27 名（14 名接受厄达替尼治疗；13 名接受化疗）为日本人。治疗组和总体人群的基线特征基本相似，但日本患者中男性较多，体重较低，且上尿路原发肿瘤较多。与化疗相比，厄达替尼改善了 OS（中位 25.4 个月 vs 12.4 个月）、PFS（中位 8.4 个月 vs 2.9 个月）和 ORR（57.1% vs 15.4%）。两种治疗方案的所有患者均出现了任何级别治疗相关不良事件（AE），但厄达替尼组的 3/4 级 AE 和导致停药的 AE 发生率较低。在日本亚组中未观察到新的安全性信号。
在日本亚组中，与化疗相比，厄达替尼改善了生存和缓解情况，且无新的安全性问题。这些结果支持厄达替尼作为 FGFR 改变的日本 mUC 患者的治疗选择，并且应考虑在诊断 mUC 后早期进行 FGFR 检测。
