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

Author:

Hahn Andrew W1ORCID,Surasi Devaki Shilpa2,Viscuse Paul V3,Bathala Tharakeswara K2,Wiele Andrew J4,Campbell Matthew T1,Zurita Amado J1,Shah Amishi Y1,Jonasch Eric1ORCID,Gao Jianjun1ORCID,Goswami Sangeeta1,Alhalabi Omar1ORCID,Rao Priya5,Sircar Kanishka5ORCID,Tannir Nizar M1ORCID,Msaouel Pavlos167ORCID

Affiliation:

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

2. Department of Nuclear Medicine, Division of Diagnostic Imaging, The University of Texas MD Anderson Cancer Center , Houston, TX , USA

3. Division of Hematology/Oncology, Department of Internal Medicine, University of Virginia Cancer Center, University of Virginia , Charlottesville, VA , USA

4. Department of Hematology/Oncology, Edward-Elmhurst Medical Group , Elmhurst, IL , USA

5. Department of Pathology, Division of Pathology/Lab Medicine, The University of Texas MD Anderson Cancer Center , Houston, TX , USA

6. Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center , Houston, TX , USA

7. David H. Koch Center for Applied Research of Genitourinary Cancers, The University of Texas, MD Anderson Cancer Center , Houston , USA

Abstract

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.

Funder

Cancer Center Support Grant to MD Anderson Cancer Center

Rob Heyvaert and Paul Heynen Prostate Cancer Foundation Young Investigator Award

Andrew Sabin Family Foundation Fellowship, Gateway for Cancer Research, a Translational Research Partnership Award

United States Department of Defense, an Advanced Discovery Award by the Kidney Cancer Association, a Translational Research Award

Publisher

Oxford University Press (OUP)

Subject

Cancer Research,Oncology

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