Department of Urology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Department of Urology, Nagoya University, Nagoya, Japan.
Int J Urol. 2022 Jul;29(7):647-655. doi: 10.1111/iju.14861. Epub 2022 Mar 18.
Pembrolizumab, an anti-PD-1 monoclonal antibody, revolutionized the treatment for advanced urothelial carcinoma. However, the standard treatment for patients after disease progression with pembrolizumab had not been established until the recent approval of enfortumab vedotin. We analyzed the treatment of these patients in the real world, and the patient background and outcomes.
We extracted data from 543 patients who experienced progressive disease after pembrolizumab initiation from a Japanese nation-wide cohort of platinum-refractory, metastatic urothelial carcinoma.
The median overall survival of the 543 patients was 3.5 months (95% confidence interval 3.0-4.1). Of these, only 20.6% (n = 112) received chemotherapy as a subsequent systemic treatment after progressive disease. The regimen of chemotherapy was very diverse. The median overall survival was 11.9 months (95% confidence interval 9.2-14.7) for patients who received chemotherapy, compared to 2.4 months for those who did not receive chemotherapy (95% confidence interval 2.1-2.9; P < 0.0001). Patients who received subsequent chemotherapy were more likely to have better performance status, neutrophil-to-lymphocyte ratio <3, hemoglobin >11 mg/dL, and history of a single chemotherapeutic regimen at pembrolizumab initiation.
This report highlights the real-world practice of the management after pembrolizumab treatment failure in the pre-enfortumab vedotin era, characterized by infrequent use of subsequent anticancer therapy comprising various regimens, reflecting the lack of a standard treatment. Clinical introduction of enfortumab vedotin is expected to improve treatment outcomes in this setting. The present study will provide important baseline data for evaluating the influence of enfortumab vedotin on clinical practices and outcomes.
抗 PD-1 单克隆抗体 pembrolizumab 彻底改变了晚期尿路上皮癌的治疗方法。然而，在 enfortumab vedotin 最近获得批准之前，对于 pembrolizumab 治疗后疾病进展的患者，尚未确立标准治疗方法。我们分析了这些患者在真实世界中的治疗方法、患者背景和结局。
我们从日本铂类难治性转移性尿路上皮癌全国性队列中提取了 543 例 pembrolizumab 治疗后疾病进展患者的数据。
543 例患者的中位总生存期为 3.5 个月（95%置信区间为 3.0-4.1）。其中，仅有 20.6%（n=112）的患者在疾病进展后接受化疗作为后续系统性治疗。化疗方案非常多样化。接受化疗的患者中位总生存期为 11.9 个月（95%置信区间为 9.2-14.7），而未接受化疗的患者中位总生存期为 2.4 个月（95%置信区间为 2.1-2.9；P<0.0001）。接受后续化疗的患者的表现状态更好、中性粒细胞与淋巴细胞比值<3、血红蛋白>11mg/dL 和 pembrolizumab 起始时接受单一化疗方案的可能性更高。
本报告强调了在 enfortumab vedotin 时代之前，pembrolizumab 治疗失败后的管理的真实世界实践，其特点是后续抗癌治疗的使用频率较低，包括各种方案，反映出缺乏标准治疗方法。enfortumab vedotin 的临床应用有望改善该环境下的治疗结局。本研究将为评估 enfortumab vedotin 对临床实践和结局的影响提供重要的基线数据。
