纳武单抗联合伊匹单抗治疗转移性组织学变异型（非透明细胞）肾细胞癌患者的疗效与安全性。

Efficacy and safety of nivolumab plus ipilimumab in patients with metastatic variant histology (non-clear cell) renal cell carcinoma.

作者信息

Moussa Mohammad Jad, Khandelwal Jaanki, Wilson Nathaniel R, Malikayil Kiran L, Surasi Devaki Shilpa, Bathala Tharakeswara K, Lin Yiyun, Rao Priya, Tamboli Pheroze, Sircar Kanishka, Ajufo Helen, Elsayes Khaled M, Shah Amishi, Johns Andrew C, Goswami Sangeeta, Hasanov Elshad, Jonasch Eric, Msaouel Pavlos, Campbell Matthew T, Alhalabi Omar, Tannir Nizar M

机构信息

Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.

Hematology and Medical Oncology Department, Baylor University Medical Center at Dallas, Dallas, Texas, USA.

出版信息

J Immunother Cancer. 2025 Feb 12;13(2):e010958. doi: 10.1136/jitc-2024-010958.

DOI:10.1136/jitc-2024-010958

PMID:39939142

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11822430/

Abstract

BACKGROUND

Nivolumab plus ipilimumab (nivo/ipi) is a standard of care first-line (1 L) therapy for patients with metastatic clear-cell renal cell carcinoma (ccRCC), but its role in patients with metastatic, non-ccRCC has not been fully defined. We report a single-institution experience with nivo/ipi in non-ccRCC.

METHODS

Between November 2017 and February 2024, 55 patients with metastatic non-ccRCC received nivo/ipi at MD Anderson Cancer Center. The tumor response was assessed by blinded radiologists using RECIST v1.1. The overall response rate (ORR), progression-free survival (PFS), PFS milestone, duration of response (DoR), and overall survival (OS) were determined. Next-generation sequencing (NGS) was performed on available tumor specimens.

RESULTS

Twenty-five (45.5%) patients had papillary histology (pRCC), 12 (21.8%) patients had chromophobe (chRCC), and 18 (32.7%) patients had unclassified RCC (uRCC). Fifty-two (94.5%) patients received nivo/ipi in 1 L. Sarcomatoid features (SF) were found in 20 (36.4%) cases. ORR was 48% (12/25) in pRCC, 25% (3/12) in chRCC (all 3 cases had SF), 27.8% (5/18) in uRCC, and 55% (11/20) across histologies with SF.The median PFS was 10.6 months (95% CI: 2.8 to 22.8) in pRCC, 3.6 months (95% CI: 0.9 - NE) in chRCC, and 3 months (95% CI: 2.1 to 7) in uRCC; 6-month milestone PFS was 56% (95% CI: 36.3 to 75.7), 41.7% (95% CI: 22 to 61.3), and 38.9% (95% CI: 21.7 to 56.1) in pRCC, chRCC, and uRCC, respectively. The median DoR for the entire cohort was 8.5 months (95% CI: 8 - NE). The median OS was 36.7 months (95% CI: 11.5 to 54.8) in pRCC, 25.7 months (95% CI: 0.9 - NE) in chRCC, and 11.1 months (95% CI: 6.5 - NE) in uRCC.Ten (18.2%) patients discontinued treatment due to treatment-related adverse events (AEs). Grade 3/4 immune-mediated AEs were noted in 17 (30.9%) patients. We performed NGS on 26 cases: (42%), (23%), and (23%) alterations were most frequently found, with and mutations enriched in pRCC and chRCC, respectively.

CONCLUSION

Nivo/ipi produced favorable outcomes in patients with pRCC supporting its use as 1 L therapy. Responses in patients with chRCC were noted exclusively with SF. Despite achieving an ORR of 27.8% with nivo/ipi, patients with uRCC had short PFS and inferior OS.

摘要

背景

纳武利尤单抗联合伊匹木单抗（nivo/ipi）是转移性透明细胞肾细胞癌（ccRCC）患者的一线（1L）标准治疗方案，但其在转移性非ccRCC患者中的作用尚未完全明确。我们报告了在非ccRCC患者中使用nivo/ipi的单机构经验。

方法

2017年11月至2024年2月期间，55例转移性非ccRCC患者在MD安德森癌症中心接受了nivo/ipi治疗。由盲法放射科医生使用RECIST v1.1评估肿瘤反应。确定总缓解率（ORR）、无进展生存期（PFS）、PFS里程碑、缓解持续时间（DoR）和总生存期（OS）。对可用的肿瘤标本进行二代测序（NGS）。

结果

25例（45.5%）患者为乳头状组织学（pRCC），12例（21.8%）患者为嫌色细胞癌（chRCC），18例（32.7%）患者为未分类肾细胞癌（uRCC）。52例（94.5%）患者在一线接受nivo/ipi治疗。20例（36.4%）病例发现有肉瘤样特征（SF）。pRCC的ORR为48%（12/25），chRCC为25%（3/12）（所有3例均有SF），uRCC为27.8%（5/18），有SF的所有组织学类型的ORR为55%（11/20）。pRCC的中位PFS为10.6个月（95%CI：2.8至22.8），chRCC为3.6个月（95%CI：0.9 - 未达到），uRCC为3个月（95%CI：2.1至7）；pRCC、chRCC和uRCC的6个月PFS里程碑分别为56%（95%CI：36.3至75.7）、41.7%（95%CI：22至61.3）和38.9%（95%CI：21.7至56.1）。整个队列的中位DoR为8.5个月（95%CI：8 - 未达到）。pRCC的中位OS为36.7个月（95%CI：11.5至54.8），chRCC为25.7个月（95%CI：0.9 - 未达到），uRCC为11.1个月（95%CI：6.5 - 未达到）。10例（18.2%）患者因治疗相关不良事件（AE）停药。17例（30.9%）患者出现3/4级免疫介导的AE。我们对26例病例进行了NGS：（42%）、（23%）和（23%）改变最常被发现，和突变分别在pRCC和chRCC中富集。