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A Multi-institutional, Retrospective Analysis of Patients with Metastatic Renal Cell Carcinoma to Bone Treated with Combination Ipilimumab and Nivolumab

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Abstract

Background

Bone metastases (BM) in renal cell carcinoma (RCC) patients are associated with poor outcomes. There are limited published data on outcomes in these patients with immunotherapy agents. We present a multi-institutional, retrospective analysis of metastatic RCC patients with BM treated with ipilimumab and nivolumab (I + N).

Objective

Patient, tumor, and treatment-related variables were retrospectively collected from electronic medical records of patients with a histologically confirmed diagnosis of RCC and at least one radiographically confirmed BM prior to initiation of I + N. Best objective response was assessed by clinical chart review, imaging reports, and treating physician evaluation; progression-free survival (PFS) and overall survival (OS) were recorded as of 31 December 2020. Descriptive statistics were used to summarize patient characteristics and BM-related variables. Kaplan-Meier method and Mantel-Haenszel log-rank test were used to compare survival among groups. Cox regression univariable and multivariable models were used to correlate patient- and treatment-related variables to outcomes.

Results

Eighty patients with RCC and BM treated with I + N were identified. Patients were predominantly male and Caucasian presenting primarily with IMDC intermediate or poor-risk clear-cell RCC. Best response to I + N was progressive disease (46%), stable disease (28%), partial response (21%), and not evaluable (5%). Median PFS was 6.1 months (95% CI 3.8–8.9 months) with the majority of patients (65%) discontinuing I + N due to disease progression. Median OS was 25.6 months (95% CI 14.9–NA) with median follow-up of 25.2 months. A multivariable regression model for PFS showed several variables to be significantly associated with worse PFS including female gender [p = 0.02; hazard ratio (HR) 2.16; 95% CI 1.14–4.12], metastases to other sites (p = 0.006; HR 2.12; 95% CI 1.24–3.62) and presence of BM to ribs (p = 0.0007; HR 2.61; 95% CI 1.50–4.52). A multivariable Cox model of OS showed no prior radiation therapy to BM (p = 0.02; HR 2.17; 95% CI 1.13–4.17) and presence of liver metastases (p = 0.0006; HR 3.19; 95% CI 1.65–6.19) to be significantly associated with worse OS.

Conclusion

RCC patients with ≥ 1 BM who received I + N therapy had a relatively low response rate, PFS, and OS. Strategies to improve outcomes in this subset of patients are needed.

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Authors and Affiliations

  1. Department of Internal Medicine, Cleveland Clinic, 9500 Euclid Avenue, NA10, Cleveland, OH, 44195, USA

    Kunal Desai

  2. Duke Cancer Institute Center for Prostate and Urologic Cancers, Durham, NC, USA

    Landon Brown, Chester Kao, Emily Kinsey & Tian Zhang

  3. Division of Medical Oncology, Department of Medicine, Duke University, DUMC Box 103861, Durham, NC, 27710, USA

    Landon Brown, Chester Kao, Emily Kinsey & Tian Zhang

  4. Department of Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic, 9620 Carnegie Ave., Cleveland, OH, 44195, USA

    Wei Wei

  5. Department of Medicine, Division of Hematology and Oncology, Vanderbilt University Medical Center, Vanderbilt-Ingram Cancer Center, Nashville, TN, USA

    Matthew Tucker & Kathryn Beckermann

  6. Genitourinary Oncology, Department of Hematology and Medical Oncology, Taussig Cancer Center, Cleveland Clinic, 9500 Euclid Ave, CA-60, Cleveland, OH, 44195, USA

    Moshe C. Ornstein

  7. Division of Hematology and Oncology, Department of Internal Medicine, Vanderbilt University, 777 PRB, 2220 Pierce Avenue, Nashville, TN, 37232, USA

    Matthew Tucker, Brian Rini & Kathryn Beckermann

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  1. Kunal Desai
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Correspondence to Moshe C. Ornstein.

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Funding

No external funding was used in the preparation of this article.

Conflict of Interest

Dr. Kunal Desai declares the following relationship: Consulting with Tyra BioSciences and CinRx. Dr. Landon Brown declares the following relationships: Consulting with Seattle Genetics. Wei Wei declares that he has no conflicts of interest that might be relevant to the contents of this article. Dr. Matthew Tucker declares that he has no conflicts of interest that might be relevant to the contents of this article. Dr. Chester Kao declares that he has no conflicts of interest that might be relevant to the contents of this article. Dr. Emily Kinsey declares that she has no conflicts of interest that might be relevant to the contents of this article. Dr Brian Rini declares the following relationships: Research funding (to Vanderbilt University) from Pfizer, Hoffman-LaRoche, Incyte, AstraZeneca, Taris, Seattle Genetics, Arrowhead Pharmaceuticals, Immunomedics, BMS, Mirati Therapeutics, Merck, Surface Oncology, Dragonfly Therapeutics, Aravive and Exelixis; Consulting with Bristol Myer Squibb, Pfizer, Roche/Genentech, Aveo, Synthorx, Compugen, Merck, Corvus, Surface Oncology, 3DMedicines, Aravive, Alkermes, Arrowhead, GSK, Shionogi, and Eisai. Stock ownership in PTC Therapeutics. Dr. Kathryn Beckermann declares the following relationships: Research funding (to Vanderbilt) from BMS-IASLC-LCFA for a young investigator award. Consulting with Exelexis. Dr. Tian Zhang declares the following relationships: Research funding (to Duke University) from Pfizer, Janssen, Acerta, Abbvie, Novartis, Merrimack, OmniSeq, PGDx, Merck, Mirati, Astellas, and Genentech; Speaking with Genomic Health and Sanofi Aventis; Consulting with AstraZeneca, Bayer, Pfizer, Foundation Medicine, Janssen, Merck, Amgen, MJH Associates, and BMS. Stock ownership/employment (spouse) from Capio Biosciences, Archimmune Therapeutics and Nanorobotics. Dr. Moshe Ornstein declares the following relationships: Consulting with BMS, Merck, Pfizer, Aveo, Exelixis, and Eisai.

Ethics approval

Collection and analysis of patient-level data for this article was approved by the participating institutions (Cleveland Clinic IRB-approved protocol 19-609, Duke University IRB-approved protocol Pro00101984, and Vanderbilt University IRB-approved protocol 160979).

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The need for written consent from patients was waived per above approval protocols.

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Not applicable.

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Authors’ Contribution

Dr. Desai wrote the majority of the content of the manuscript and collected patient data for Cleveland Clinic. Drs. Brown and Tucker edited the manuscript and collected patient data at Duke University and Vanderbilt University, respectively. Mr. Wei Wei conducted the statistical analysis for this article and wrote the statistics-related content. Drs. Kao and Kinsey collected patient data for Duke University. Drs. Rini, Beckermann, Zhang, and Ornstein provided editorial input for the article.

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Desai, K., Brown, L., Wei, W. et al. A Multi-institutional, Retrospective Analysis of Patients with Metastatic Renal Cell Carcinoma to Bone Treated with Combination Ipilimumab and Nivolumab. Targ Oncol 16, 633–642 (2021). https://doi.org/10.1007/s11523-021-00832-3

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