Ged Yasser, Touma Amina, Meza Contreras Luis, Elias Roy, Van Galen Joseph, Cupo Olivia, Baraban Ezra, Singla Nirmish, Lee Chung-Han, Pal Sumanta, Zibelman Matthew, Kotecha Ritesh R
Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD.
Department of Medical Oncology, City of Hope Comprehensive Cancer Center, Duarte, CA.
J Immunother. 2025 Apr 1;48(3):113-117. doi: 10.1097/CJI.0000000000000549. Epub 2025 Feb 4.
Metastatic translocation renal cell carcinomas (mtRCCs) are rare and aggressive tumors with limited treatment options. Recent studies demonstrated promising activity of immune-oncology (IO) combinations in mtRCC. However, the effectiveness of dual IO combinations versus IO plus VEGF-TKI combinations remains unclear. We conducted a retrospective analysis of IO combinations in mtRCC patients at 4 institutions. Eligible patients had confirmed mtRCC by genitourinary pathologist and received IO combination therapy (IO+IO or IO+VEGF-TKI). Clinical data and treatment outcomes were recorded from the start of systemic therapy. Objective response rate (ORR) was retrospectively evaluated, and time to treatment failure (TTF), and overall survival (OS) were compared for IO+IO and IO+VEGF-TKI groups. We identified 22 mtRCC patients who received IO combinations, all confirmed to have TFE3 rearrangement by FISH. Most patients were female (68%) with a median age of 41 years (16-79). Treatment breakdown included: IO+IO (n=8, 36%) and IO+VEGF-TKI (n=14, 64%). In the evaluable patients for the efficacy analysis, ORR was 14% (1/7) for the IO+IO group and 54% (6/11) for the IO+VEGF-TKI group. With a median follow-up of 32.4 months, the median TTF was 1.2 months and 6.2 months in the IO+IO and IO+VEGF-TKI groups, respectively ( P =0.12). There was no statistically significant difference in median OS between both groups, 36.7 months in the IO+IO group and 15.6 months in IO+VEGF-TKI ( P =0.9). Our findings demonstrate that IO+VEGF-TKI resulted in higher ORR and TTF point estimates without statistically detectable differences, compared with IO+IO therapy. Larger studies are needed to validate these findings and optimize treatment selection.
转移性易位性肾细胞癌（mtRCC）是罕见的侵袭性肿瘤，治疗选择有限。最近的研究表明，免疫肿瘤学（IO）联合疗法在mtRCC中显示出有前景的活性。然而，双IO联合疗法与IO加VEGF-TKI联合疗法的有效性仍不明确。我们对4家机构的mtRCC患者的IO联合疗法进行了回顾性分析。符合条件的患者经泌尿生殖病理学家确诊为mtRCC，并接受了IO联合疗法（IO+IO或IO+VEGF-TKI）。从全身治疗开始记录临床数据和治疗结果。回顾性评估客观缓解率（ORR），并比较IO+IO组和IO+VEGF-TKI组的治疗失败时间（TTF）和总生存期（OS）。我们确定了22例接受IO联合疗法的mtRCC患者，所有患者均通过荧光原位杂交（FISH）确诊为TFE3重排。大多数患者为女性（68%），中位年龄为41岁（16-79岁）。治疗分类包括：IO+IO（n=8，36%）和IO+VEGF-TKI（n=14，64%）。在可评估疗效分析的患者中，IO+IO组的ORR为14%（1/7），IO+VEGF-TKI组为54%（6/11）。中位随访32.4个月，IO+IO组和IO+VEGF-TKI组的中位TTF分别为1.2个月和6.2个月（P=0.12）。两组的中位OS无统计学显著差异，IO+IO组为36.7个月，IO+VEGF-TKI组为15.6个月（P=0.9）。我们的研究结果表明，与IO+IO疗法相比，IO+VEGF-TKI导致更高的ORR和TTF点估计值，但无统计学可检测差异。需要更大规模的研究来验证这些发现并优化治疗选择。
