Talukder Rafee, Bakaloudi Dimitra Rafailia, Makrakis Dimitrios, Diamantopoulos Leonidas N, Enright Thomas, Leary Jacob B, Raychaudhuri Ruben, Tripathi Nishita, Agarwal Neeraj, Jindal Tanya, Brown Jason R, Zakharia Yousef, Rey-Cárdenas Macarena, Castellano Daniel, Nguyen Charles B, Alva Ajjai, Zakopoulou Roubini, Bamias Aristotelis, Barrera Rafael Morales, Marmolejo David, Drakaki Alexandra, Pinato David J, Korolewicz James, Buznego Lucia Alonso, Duran Ignacio, Carballeira Clara Castro, McKay Rana R, Stewart Tyler F, Gupta Shilpa, Barata Pedro, Yu Evan Y, Koshkin Vadim S, Khaki Ali Raza, Grivas Petros
Department of Medicine, University of Washington, Seattle, WA; Department of Medicine, Section of Hematology and Oncology, Baylor College of Medicine, Houston, TX.
Department of Medicine, University of Washington, Seattle, WA.
Clin Genitourin Cancer. 2025 Feb;23(1):102284. doi: 10.1016/j.clgc.2024.102284. Epub 2024 Dec 2.
FGFR2/3, MTAP and ERBB2 genomic alterations have treatment targets in advanced urothelial carcinoma (aUC). These alterations may affect tumor microenvironment and outcomes with immune checkpoint inhibitors (ICIs) in aUC.
We identified patients with available genomic data in our multi-institution cohort of patients with aUC treated with ICI. Outcomes (observed response rate [ORR], progression-free and overall survival [PFS, OS]) with ICI were compared between patients with and without FGFR 2/3, MTAP, ERBB2 alterations. We compared ORR using logistic regression and PFS/OS using Cox proportional hazards.
Out of 1,514 patients, 276 (18%), 174 (11%) and 208 (14%) patients had known FGFR2/3, MTAP and ERBB2 alteration status, respectively. and were treated with ICI in 1L or 2 + L. In patients with (vs. without) FGFR2/3 alteration, ORR with ICI was 21% vs. 32% (OR 0.54; [95%CI 0.32-0.91]), PFS was significantly shorter in patients with FGFR2/3 alterations (HR = 1.36 [95%CI 1.03-1.80]; P=0.03); OS was not significantly different (HR = 1.22 [95%CI 0.86-1.47]). In patients with (vs. without) MTAP alteration, ORR with ICI was 25% versus 40% (OR 0.52 [95%CI 0.20-1.38]); PFS and OS were nonsignificantly different. In patients with (vs. without) ERBB2 alteration, ORR with ICI was similar (37% vs. 35%; OR 1.06; 95%CI 0.57-1.97); PFS and OS were significantly longer in patients with ERBB2 alteration [HR 0.63 (95%CI 0.41-0.95); P=0.03; HR 0.66, [95% CI 0.44-0.97]), respectively.
Our results support further evaluation of FGFR2/3, MTAP and ERBB2 alterations as putative biomarkers in patients with aUC treated with ICI.
FGFR2/3、MTAP和ERBB2基因改变在晚期尿路上皮癌（aUC）中有治疗靶点。这些改变可能会影响aUC患者使用免疫检查点抑制剂（ICI）的肿瘤微环境和治疗结果。
我们在接受ICI治疗的多机构aUC患者队列中识别出有可用基因数据的患者。比较了有和没有FGFR 2/3、MTAP、ERBB2改变的患者使用ICI的治疗结果（观察到的缓解率[ORR]、无进展生存期和总生存期[PFS、OS]）。我们使用逻辑回归比较ORR，使用Cox比例风险模型比较PFS/OS。
在1514例患者中，分别有276例（18%）、174例（11%）和208例（14%）患者已知FGFR2/3、MTAP和ERBB2改变状态，并接受了一线或二线及以上ICI治疗。在有（vs.无）FGFR2/3改变的患者中，ICI治疗的ORR分别为21%和32%（OR 0.54；[95%CI 0.32 - 0.91]），FGFR2/3改变的患者PFS显著缩短（HR = 1.36 [95%CI 1.03 - 1.80]；P = 0.03）；OS无显著差异（HR = 1.22 [95%CI 0.86 - 1.47]）。在有（vs.无）MTAP改变的患者中，ICI治疗的ORR分别为25%和40%（OR 0.52 [95%CI 0.20 - 1.38]）；PFS和OS无显著差异。在有（vs.无）ERBB2改变的患者中，ICI治疗的ORR相似（37% vs. 35%；OR 1.06；95%CI 0.57 - 1.97）；有ERBB2改变的患者PFS和OS显著更长[HR 0.63（95%CI 0.41 - 0.95）；P = 0.03；HR 0.66，[95%CI 0.44 - 0.97]）。
我们的结果支持进一步评估FGFR2/3、MTAP和ERBB2改变作为接受ICI治疗的aUC患者的潜在生物标志物。
