Oya Mototsugu, Yasuoka Shotaro, Tokudome Takuto, Minegishi Toshihiko, Hamada Masahiro, Ozaki Masahiko, Maekawa Shinichiroh, Ito Yuichiro
Department of Urology, Keio University School of Medicine, Tokyo, Japan.
Oncology Medical Affairs, MSD K.K., 1‑13‑12 Kudan‑kita, Chiyoda‑ku, Tokyo, 102‑8667, Japan.
Int J Clin Oncol. 2025 Apr 29. doi: 10.1007/s10147-025-02708-2.
Post-marketing surveillance focusing on hepatic function disorder was requested owing to its higher incidence in the pembrolizumab plus axitinib group than in the sunitinib group in KEYNOTE-426. We aimed to evaluate the prevalence and risk factors of adverse events (AEs) of hepatic function disorder in patients with unresectable/metastatic renal cell carcinoma (RCC) treated with pembrolizumab plus axitinib in real-world clinical practice in Japan.
Patients were observed for 9 months after starting treatment with pembrolizumab plus axitinib.
In total, 193 patients were included in the safety analysis set (median age, 70 years). Most patients did not have a history of hepatic function disorder before starting treatment (96.4%, 186/193). The median treatment period was 27.1 weeks. At the 9-month data cut-off, 62.2% (120/193) of patients discontinued treatment, the most common reason being any AE in 31.1% (60/193). The incidence of AEs of hepatic function disorder was 30.1% (58/193) for any grade and 15.0% (29/193) for grade ≥ 3. Most AEs of hepatic function disorder occurred within 3 months from starting treatment. AEs of hepatic function disorder were the reason for discontinuation of pembrolizumab in 9.3% (18/193) of patients; axitinib, 7.3% (14/193); and both pembrolizumab and axitinib, 5.2% (10/193). No background factors were identified as being associated with the occurrence of AEs of hepatic function disorder.
There were no new safety signals for AEs of hepatic function disorder, and the incidence was consistent with that reported in KEYNOTE-426, in Japanese patients with radically unresectable/metastatic RCC treated with pembrolizumab plus axitinib.
在KEYNOTE-426研究中,帕博利珠单抗联合阿昔替尼组肝功能障碍的发生率高于舒尼替尼组,因此要求开展针对肝功能障碍的上市后监测。我们旨在评估在日本真实世界临床实践中,接受帕博利珠单抗联合阿昔替尼治疗的不可切除/转移性肾细胞癌(RCC)患者肝功能障碍不良事件(AE)的发生率及危险因素。
患者在开始接受帕博利珠单抗联合阿昔替尼治疗后观察9个月。
安全性分析集共纳入193例患者(中位年龄70岁)。大多数患者在开始治疗前无肝功能障碍病史(96.4%,186/193)。中位治疗周期为27.1周。在9个月数据截止时,62.2%(120/193)的患者停止治疗,最常见的原因是任何不良事件,占31.1%(60/193)。任何级别肝功能障碍不良事件的发生率为30.1%(58/193),≥3级为15.0%(29/193)。大多数肝功能障碍不良事件发生在开始治疗后的3个月内。肝功能障碍不良事件是18例(9.3%,18/193)患者停用帕博利珠单抗的原因;14例(7.3%,14/193)患者停用阿昔替尼;10例(5.2%,10/193)患者同时停用帕博利珠单抗和阿昔替尼。未发现与肝功能障碍不良事件发生相关的背景因素。
在接受帕博利珠单抗联合阿昔替尼治疗的日本根治性不可切除/转移性RCC患者中,未发现肝功能障碍不良事件的新安全信号,其发生率与KEYNOTE-426研究报告一致。