Department of Medical Oncology, Vall d'Hebron Institute of Oncology, Vall d' Hebron University Hospital, Universitat Autònoma de Barcelona, Passeig Vall d'Hebron 119-129, 08035, Barcelona, Catalonia, Spain.
Oncology Data Science (OdysSey) Group, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain.
Clin Transl Oncol. 2023 Dec;25(12):3556-3564. doi: 10.1007/s12094-023-03213-6. Epub 2023 May 22.
We evaluated the prevalence of immune-related adverse events and anti-tumor efficacy in advanced/metastatic urothelial carcinoma following immune-checkpoint inhibitors (ICIs) treatment.
We conducted a multicenter retrospective study of patients with advanced/metastatic urothelial carcinoma treated with ICIs in four Spanish institutions. irAEs were classified using Common Terminology Criteria for Adverse Event (CTCAE) v.5.0 guidelines. The primary endpoint was overall survival (OS). Other endpoints were overall response rate (ORR) and progression-free survival (PFS). irAEs were evaluated as a time-dependent covariate to avoid immortal time bias.
A total of 114 patients were treated with ICIs between May 2013 and May 2019, 105 (92%) of whom received ICIs as monotherapy. irAEs of any grade were experienced in 56 (49%) patients and 21 (18%) patients had grade ≥ 3 toxicity. The most frequent irAEs were gastrointestinal and dermatological toxicities, reported in 25 (22%) and 20 (17%) patients, respectively. Patients with grade 1-2 irAEs had significantly longer OS compared to those without grade 1-2 irAEs (median 18.2 vs. 8.7 months, HR = 0.61 [95% CI 0.39-0.95], p = 0.03). No association with efficacy was observed for patients with grade ≥ 3 irAEs. No difference in PFS was observed after adjusting for the immortal time bias. ORR was higher in patients who developed irAEs (48% vs 17%, p < 0.001).
Our findings suggest that development of irAEs was associated with higher ORR, and patients who developed grade 1-2 irAEs had longer OS. Prospective studies are necessary to confirm our findings.
我们评估了免疫检查点抑制剂（ICI）治疗后晚期/转移性尿路上皮癌患者的免疫相关不良事件（irAE）发生率和抗肿瘤疗效。
我们对四家西班牙机构的 114 名接受 ICI 治疗的晚期/转移性尿路上皮癌患者进行了多中心回顾性研究。irAE 使用不良事件通用术语标准（CTCAE）v.5.0 指南进行分类。主要终点是总生存期（OS）。其他终点包括总缓解率（ORR）和无进展生存期（PFS）。irAE 被评估为一个时间依赖性协变量，以避免 Immortal Time Bias。
共 114 例患者于 2013 年 5 月至 2019 年 5 月期间接受 ICI 治疗，其中 105 例（92%）接受 ICI 单药治疗。56 例（49%）患者出现任何级别的 irAE，21 例（18%）患者出现≥3 级毒性。最常见的 irAE 是胃肠道和皮肤毒性，分别有 25 例（22%）和 20 例（17%）患者出现。有 1-2 级 irAE 的患者的 OS 明显长于无 1-2 级 irAE 的患者（中位 OS 18.2 个月与 8.7 个月，HR=0.61[95%CI 0.39-0.95]，p=0.03）。有≥3 级 irAE 的患者与疗效无相关性。在调整 Immortal Time Bias 后，PFS 无差异。发生 irAE 的患者 ORR 更高（48%比 17%，p<0.001）。
我们的研究结果表明，irAE 的发生与更高的 ORR 相关，发生 1-2 级 irAE 的患者 OS 更长。需要前瞻性研究来证实我们的发现。
