Treatment Outcomes in Patients With Metastatic Renal Cell Carcinoma With Sarcomatoid and/or Rhabdoid Dedifferentiation After Progression on Immune Checkpoint Therapy

Authors

Andrew W Hahn
Devaki Shilpa Surasi
Paul V Viscuse
Tharakeswara K Bathala
Andrew J Wiele
Matthew T Campbell
Amado J Zurita
Amishi Y Shah
Eric Jonasch
Jianjun Gao
Sangeeta Goswami
Omar Alhalabi
Priya Rao
Kanishka Sircar
Nizar M Tannir
Pavlos Msaouel

Publication Date

5-3-2024

Journal

The Oncologist

Abstract

BACKGROUND: Metastatic RCC with sarcomatoid and/or rhabdoid (S/R) dedifferentiation is an aggressive disease associated with improved response to immune checkpoint therapy (ICT). The outcomes of patients treated with VEGFR-targeted therapies (TT) following ICT progression have not been investigated.

PATIENTS AND METHODS: Retrospective review of 57 patients with sarcomatoid (S), rhabdoid (R), or sarcomatoid plus rhabdoid (S + R) dedifferentiation who received any TT after progression on ICT at an academic cancer center. Clinical endpoints of interest included time on TT, overall survival (OS) from initiation of TT, and objective response rate (ORR) by RECIST version 1.1. Multivariable models adjusted for epithelial histology, IMDC risk, prior VEGFR TT, and inclusion of cabozantinib in the post-ICT TT regimen.

RESULTS: 29/57 patients had S dedifferentiation and 19 had R dedifferentiation. The most frequently used TT was cabozantinib (43.9%) followed by selective VEGFR TT (22.8%). The median time on TT was 6.4 months for all, 6.1 months for those with S dedifferentiation, 15.6 months for R dedifferentiation, and 6.1 months for S + R dedifferentiation. Median OS from initiation of TT was 24.9 months for the entire cohort, and the ORR was 20.0%. Patients with R dedifferentiation had significantly longer time on TT than those with S dedifferentiation (HR 0.44, 95% CI, 0.21-0.94). IMDC risk was associated with OS.

CONCLUSIONS: A subset of patients with S/R dedifferentiation derive clinical benefit from TT after they have progressive disease on ICT. Patients with R dedifferentiation appeared to derive more benefit from TT than those with S dedifferentiation.

Keywords

Humans, Carcinoma, Renal Cell, Female, Male, Middle Aged, Immune Checkpoint Inhibitors, Aged, Retrospective Studies, Kidney Neoplasms, Treatment Outcome, Adult, Cell Dedifferentiation, Disease Progression, Anilides

Comments

Supplementary Materials

PMID: 38035767