Faculty, Staff and Student Publications

Publication Date

2-12-2025

Journal

The Journal for ImmunoTherapy of Cancer

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: TP53 (42%), PTEN (23%), and TERT (23%) alterations were most frequently found, with TERT and TP53 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.

Keywords

Humans, Nivolumab, Ipilimumab, Male, Carcinoma, Renal Cell, Female, Middle Aged, Aged, Kidney Neoplasms, Antineoplastic Combined Chemotherapy Protocols, Adult, Aged, 80 and over, Retrospective Studies, Immunotherapy, Immune Checkpoint Inhibitor, Genitourinary Cancer, Kidney Cancer, Solid tumor

DOI

10.1136/jitc-2024-010958

PMID

39939142

PMCID

PMC11822430

PubMedCentral® Posted Date

2-12-2025

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

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