Department of Urology, Tokyo Medical and Dental University, Tokyo, Japan.
Department of Breast and Medical Oncology, National Cancer Center Hospital East, Kashiwa, Japan.
Cancer Med. 2020 Nov;9(22):8355-8363. doi: 10.1002/cam4.3445. Epub 2020 Sep 4.
Radiotherapy plus immune checkpoint inhibitors can potentially induce synergistic antitumor immune responses. However, little clinical evidence is established regarding their combination therapy. Here, we aimed to assess whether radiotherapy to the primary tumor impacts on the efficacy of pembrolizumab in advanced urothelial cancer. We retrospectively reviewed 98 advanced urothelial cancer patients receiving pembrolizumab in a second- or later-line setting using our multicenter cohort. Patients were categorized according to a history of radiotherapy to the primary tumor: patients previously exposed to radiotherapy to the primary tumor (Radiotherapy group, 17 patients [17%]) and those not (Nonradiotherapy group, 81 patients [83%]). The associations of radiotherapy to the primary tumor with objective response and survival were evaluated. The Radiotherapy group showed a significantly higher objective response ratio than did the Non-radiotherapy group (65% vs 19%; P < .001). The Radiotherapy group had a higher progression-free survival rate compared with the Nonradiotherapy group (52% vs 28% at 12 months; P = .078), but statistical significance was not reached. The Radiotherapy group had a significantly higher overall survival rate compared with the Non-radiotherapy group (77% vs 50% at 12 months; P = .025). From multivariate analysis, radiotherapy to the primary tumor was an independent predictor for longer overall survival (hazard ratio, 0.31; P = .032) along with Eastern Cooperative Oncology Group performance status ≤1 and the absence of visceral metastasis. Therefore, radiotherapy to the primary tumor may enhance the efficacy of pembrolizumab for patients with advanced urothelial cancer.
放疗联合免疫检查点抑制剂可能会诱发协同的抗肿瘤免疫反应。然而，关于其联合治疗的临床证据还很少。在这里，我们旨在评估原发肿瘤的放疗是否会影响帕博利珠单抗在晚期尿路上皮癌中的疗效。我们回顾性地分析了 98 例在二线或更后线接受帕博利珠单抗治疗的晚期尿路上皮癌患者的多中心队列研究。根据既往是否接受过原发灶放疗将患者分为两组：既往接受过原发灶放疗的患者（放疗组，17 例[17%]）和未接受过放疗的患者（非放疗组，81 例[83%]）。评估了原发灶放疗与客观缓解率和生存的相关性。放疗组的客观缓解率明显高于非放疗组（65%比 19%；P<0.001）。放疗组的无进展生存率高于非放疗组（12 个月时为 52%比 28%；P=0.078），但未达到统计学意义。放疗组的总生存率明显高于非放疗组（12 个月时为 77%比 50%；P=0.025）。多变量分析显示，原发灶放疗是总生存时间延长的独立预测因素（风险比，0.31；P=0.032），同时还与东部肿瘤协作组表现状态≤1 和无内脏转移有关。因此，原发灶放疗可能会增强帕博利珠单抗治疗晚期尿路上皮癌患者的疗效。
