TY - JOUR
T1 - Combination antiangiogenic tyrosine kinase inhibition and anti-PD1 immunotherapy in metastatic renal cell carcinoma
T2 - A retrospective analysis of safety, tolerance, and clinical outcomes
AU - Laccetti, Andrew L.
AU - Garmezy, Benjamin
AU - Xiao, Lianchun
AU - Economides, Minas
AU - Venkatesan, Aradhana
AU - Gao, Jianjun
AU - Jonasch, Eric
AU - Corn, Paul
AU - Zurita-Saavedra, Amado
AU - Brown, Landon C.
AU - Kao, Chester
AU - Kinsey, Emily N.
AU - Gupta, Rajan T.
AU - Harrison, Michael R.
AU - Armstrong, Andrew J.
AU - George, Daniel J.
AU - Tannir, Nizar
AU - Msaouel, Pavlos
AU - Shah, Amishi
AU - Zhang, Tian
AU - Campbell, Matthew T.
N1 - Publisher Copyright:
© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.
PY - 2021/4
Y1 - 2021/4
N2 - 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.
AB - 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.
KW - combination
KW - immunotherapy
KW - metastatic renal cell carcinoma
KW - salvage therapy
KW - tyrosine kinase inhibitor
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U2 - 10.1002/cam4.3812
DO - 10.1002/cam4.3812
M3 - Article
C2 - 33650321
AN - SCOPUS:85101944617
SN - 2045-7634
VL - 10
SP - 2341
EP - 2349
JO - Cancer Medicine
JF - Cancer Medicine
IS - 7
ER -