Combination antiangiogenic tyrosine kinase inhibition and anti‐PD1 immunotherapy in metastatic renal cell carcinoma: A retrospective analysis of safety, tolerance, and clinical outcomes
Abstract Introduction Two separate antiangiogenic tyrosine kinase inhibitors (TKIs) and immunotherapy (IO) combinations are FDA‐approved as front‐line treatment for metastatic renal cell carcinoma (mRCC). Little is known about off‐protocol and post‐front‐line experience with combination TKI–IO appro...
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Wiley
2021-04-01
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Online Access: | https://doi.org/10.1002/cam4.3812 |
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Article |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Andrew L. Laccetti Benjamin Garmezy Lianchun Xiao Minas Economides Aradhana Venkatesan Jianjun Gao Eric Jonasch Paul Corn Amado Zurita‐Saavedra Landon C. Brown Chester Kao Emily N. Kinsey Rajan T. Gupta Michael R. Harrison Andrew J. Armstrong Daniel J. George Nizar Tannir Pavlos Msaouel Amishi Shah Tian Zhang Matthew T. Campbell |
spellingShingle |
Andrew L. Laccetti Benjamin Garmezy Lianchun Xiao Minas Economides Aradhana Venkatesan Jianjun Gao Eric Jonasch Paul Corn Amado Zurita‐Saavedra Landon C. Brown Chester Kao Emily N. Kinsey Rajan T. Gupta Michael R. Harrison Andrew J. Armstrong Daniel J. George Nizar Tannir Pavlos Msaouel Amishi Shah Tian Zhang Matthew T. Campbell Combination antiangiogenic tyrosine kinase inhibition and anti‐PD1 immunotherapy in metastatic renal cell carcinoma: A retrospective analysis of safety, tolerance, and clinical outcomes Cancer Medicine combination immunotherapy metastatic renal cell carcinoma salvage therapy tyrosine kinase inhibitor |
author_facet |
Andrew L. Laccetti Benjamin Garmezy Lianchun Xiao Minas Economides Aradhana Venkatesan Jianjun Gao Eric Jonasch Paul Corn Amado Zurita‐Saavedra Landon C. Brown Chester Kao Emily N. Kinsey Rajan T. Gupta Michael R. Harrison Andrew J. Armstrong Daniel J. George Nizar Tannir Pavlos Msaouel Amishi Shah Tian Zhang Matthew T. Campbell |
author_sort |
Andrew L. Laccetti |
title |
Combination antiangiogenic tyrosine kinase inhibition and anti‐PD1 immunotherapy in metastatic renal cell carcinoma: A retrospective analysis of safety, tolerance, and clinical outcomes |
title_short |
Combination antiangiogenic tyrosine kinase inhibition and anti‐PD1 immunotherapy in metastatic renal cell carcinoma: A retrospective analysis of safety, tolerance, and clinical outcomes |
title_full |
Combination antiangiogenic tyrosine kinase inhibition and anti‐PD1 immunotherapy in metastatic renal cell carcinoma: A retrospective analysis of safety, tolerance, and clinical outcomes |
title_fullStr |
Combination antiangiogenic tyrosine kinase inhibition and anti‐PD1 immunotherapy in metastatic renal cell carcinoma: A retrospective analysis of safety, tolerance, and clinical outcomes |
title_full_unstemmed |
Combination antiangiogenic tyrosine kinase inhibition and anti‐PD1 immunotherapy in metastatic renal cell carcinoma: A retrospective analysis of safety, tolerance, and clinical outcomes |
title_sort |
combination antiangiogenic tyrosine kinase inhibition and anti‐pd1 immunotherapy in metastatic renal cell carcinoma: a retrospective analysis of safety, tolerance, and clinical outcomes |
publisher |
Wiley |
series |
Cancer Medicine |
issn |
2045-7634 |
publishDate |
2021-04-01 |
description |
Abstract Introduction Two separate antiangiogenic tyrosine kinase inhibitors (TKIs) and immunotherapy (IO) combinations are FDA‐approved as front‐line treatment for metastatic renal cell carcinoma (mRCC). Little is known about off‐protocol and post‐front‐line experience with combination TKI–IO approaches. Methods We conducted a retrospective analysis of mRCC patients who received combination TKI–IO post‐first‐line therapy between November 2015 and January 2019 at MD Anderson Cancer Center and Duke Cancer Institute. Chart review detailed patient characteristics, treatments, toxicity, and survival. Independent radiologists, blinded to clinical data, assessed best radiographic response using RECIST v1.1. Results We identified 48 mRCC patients for inclusion: median age 65 years, 75.0% clear cell histology, 68.8% IMDC intermediate risk, and median two prior systemic therapies. TKI–IO combinations included nivolumab–cabozantinib (N +C; 24 patients), nivolumab–pazopanib (N+P; 13), nivolumab–axitinib (6), nivolumab–lenvatinib (2), and nivolumab–ipilimumab–cabozantinib (3). The median progression‐free survival was 11.6 months and the median overall survival was not reached. Response data were available in 45 patients: complete response (CR; n = 3, 6.7%), partial response (PR; 20, 44.4%), stable disease (SD; 19, 42.2%), and progressive disease (3, 6.7%). Overall response rate was 51% and disease control rate (CR+PR+SD) was 93%. Only one patient had a grade ≥3 adverse event. Conclusion To our knowledge, this is the first case series reporting off‐label use of combination TKI–IO for mRCC. TKI–IO combinations, particularly N+P and N+C, are well tolerated and efficacious. Although further prospective research is essential, slow disease progression on IO or TKI monotherapy may be safely controlled with addition of either TKI or IO. |
topic |
combination immunotherapy metastatic renal cell carcinoma salvage therapy tyrosine kinase inhibitor |
url |
https://doi.org/10.1002/cam4.3812 |
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doaj-93fb0ccf60b5470ca6cdd487ce1a82ce2021-03-22T05:18:36ZengWileyCancer Medicine2045-76342021-04-011072341234910.1002/cam4.3812Combination antiangiogenic tyrosine kinase inhibition and anti‐PD1 immunotherapy in metastatic renal cell carcinoma: A retrospective analysis of safety, tolerance, and clinical outcomesAndrew L. Laccetti0Benjamin Garmezy1Lianchun Xiao2Minas Economides3Aradhana Venkatesan4Jianjun Gao5Eric Jonasch6Paul Corn7Amado Zurita‐Saavedra8Landon C. Brown9Chester Kao10Emily N. Kinsey11Rajan T. Gupta12Michael R. Harrison13Andrew J. Armstrong14Daniel J. George15Nizar Tannir16Pavlos Msaouel17Amishi Shah18Tian Zhang19Matthew T. Campbell20Genitourinary Oncology Service Department of Medicine Memorial Sloan Kettering Cancer Center New York NY USADepartment of Cancer Medicine University of Texas M.D. Anderson Cancer Center Houston TX USADepartment of Genitourinary Medical Oncology University of Texas M.D. Anderson Cancer Center Houston TX USADepartment of Internal Medicine McGovern Medical School at UTHealth Houston TX USADepartment of Radiology University of Texas M.D. Anderson Cancer Center Houston TX USADepartment of Genitourinary Medical Oncology University of Texas M.D. Anderson Cancer Center Houston TX USADepartment of Genitourinary Medical Oncology University of Texas M.D. Anderson Cancer Center Houston TX USADepartment of Cancer Medicine University of Texas M.D. Anderson Cancer Center Houston TX USADepartment of Cancer Medicine University of Texas M.D. Anderson Cancer Center Houston TX USADivision of Medical Oncology Department of Medicine Duke University Durham NC USADivision of Medical Oncology Department of Medicine Duke University Durham NC USADivision of Medical Oncology Department of Medicine Duke University Durham NC USADuke Cancer Institute Center for Prostate and Urologic Cancers Durham NC USADivision of Medical Oncology Department of Medicine Duke University Durham NC USADivision of Medical Oncology Department of Medicine Duke University Durham NC USADivision of Medical Oncology Department of Medicine Duke University Durham NC USADepartment of Genitourinary Medical Oncology University of Texas M.D. Anderson Cancer Center Houston TX USADepartment of Genitourinary Medical Oncology University of Texas M.D. Anderson Cancer Center Houston TX USADepartment of Genitourinary Medical Oncology University of Texas M.D. Anderson Cancer Center Houston TX USADivision of Medical Oncology Department of Medicine Duke University Durham NC USADepartment of Genitourinary Medical Oncology University of Texas M.D. Anderson Cancer Center Houston TX USAAbstract Introduction Two separate antiangiogenic tyrosine kinase inhibitors (TKIs) and immunotherapy (IO) combinations are FDA‐approved as front‐line treatment for metastatic renal cell carcinoma (mRCC). Little is known about off‐protocol and post‐front‐line experience with combination TKI–IO approaches. Methods We conducted a retrospective analysis of mRCC patients who received combination TKI–IO post‐first‐line therapy between November 2015 and January 2019 at MD Anderson Cancer Center and Duke Cancer Institute. Chart review detailed patient characteristics, treatments, toxicity, and survival. Independent radiologists, blinded to clinical data, assessed best radiographic response using RECIST v1.1. Results We identified 48 mRCC patients for inclusion: median age 65 years, 75.0% clear cell histology, 68.8% IMDC intermediate risk, and median two prior systemic therapies. TKI–IO combinations included nivolumab–cabozantinib (N +C; 24 patients), nivolumab–pazopanib (N+P; 13), nivolumab–axitinib (6), nivolumab–lenvatinib (2), and nivolumab–ipilimumab–cabozantinib (3). The median progression‐free survival was 11.6 months and the median overall survival was not reached. Response data were available in 45 patients: complete response (CR; n = 3, 6.7%), partial response (PR; 20, 44.4%), stable disease (SD; 19, 42.2%), and progressive disease (3, 6.7%). Overall response rate was 51% and disease control rate (CR+PR+SD) was 93%. Only one patient had a grade ≥3 adverse event. Conclusion To our knowledge, this is the first case series reporting off‐label use of combination TKI–IO for mRCC. TKI–IO combinations, particularly N+P and N+C, are well tolerated and efficacious. Although further prospective research is essential, slow disease progression on IO or TKI monotherapy may be safely controlled with addition of either TKI or IO.https://doi.org/10.1002/cam4.3812combinationimmunotherapymetastatic renal cell carcinomasalvage therapytyrosine kinase inhibitor |