@article{89ca466432d6495c8f5ad1a4116b56e1,
title = "Outcomes of patients with metastatic clear-cell renal cell carcinoma treated with second-line VEGFR-TKI after first-line immune checkpoint inhibitors",
abstract = "Background: Immune checkpoint inhibitors (ICIs)are being increasingly utilised in the front-line (1L)setting of metastatic clear-cell renal cell carcinoma (mccRCC). Limited data exist on responses and survival on second-line (2L)vascular endothelial growth factor–receptor tyrosine kinase inhibitor (VEGFR-TKI)therapy after 1L ICI therapy. Patients and methods: This is a retrospective study of mccRCC patients treated with 2L VEGFR-TKI after progressive disease (PD)with 1L ICI. Patients were treated at MD Anderson Cancer Center or Memorial Sloan Kettering Cancer Center between December 2015 and February 2018. Objective response was assessed by blinded radiologists' review using Response Evaluation Criteria in Solid Tumours v1.1. Descriptive statistics and Kaplan–Meier method were used. Results: Seventy patients were included in the analysis. Median age at mccRCC diagnosis was 59 years; 8 patients (11%)had international metastatic database consortium favourable-risk disease, 48 (69%)had intermediate-risk disease and 14 (20%)had poor-risk disease. As 1L therapy, 12 patients (17%)received anti–programmed death ligand-1 (PD-(L)1)monotherapy with nivolumab or atezolizumab, 33 (47%)received nivolumab plus ipilimumab and 25 (36%)received combination anti–PD-(L)1 plus bevacizumab. 2L TKI therapies included pazopanib, sunitinib, axitinib and cabozantinib. On 2L TKI therapy, one patient (1.5%)achieved a complete response, 27 patients (39.7%)a partial response and 36 patients (52.9%)stable disease. Median progression-free survival (mPFS)was 13.2 months (95% confidence interval: 10.1, NA). Forty-five percent of subjects required a dose reduction, and twenty-seven percent of patients discontinued treatment because of toxicity. Conclusions: In this retrospective study of patients with mccRCC receiving 2L TKI monotherapy after 1L ICI, we observed 2L antitumour activity and tolerance comparable to historical data for 1L TKI.",
keywords = "Clear cell renal cell carcinoma, Immune checkpoint inhibitor, Immunotherapy, Immunotherapy refractory, Metastatic kidney cancer, RCC, Renal cell carcinoma, Therapy sequence, VEGFR-TKI, ccRCC",
author = "Shah, {A. Y.} and Kotecha, {R. R.} and Lemke, {E. A.} and A. Chandramohan and Chaim, {J. L.} and P. Msaouel and L. Xiao and J. Gao and Campbell, {M. T.} and Zurita, {A. J.} and J. Wang and Corn, {P. G.} and E. Jonasch and Motzer, {R. J.} and P. Sharma and Voss, {M. H.} and Tannir, {N. M.}",
note = "Funding Information: A.Y.S. received research funding to employer for clinical trial support from BMS , Eisai and EMD Serono; honoraria from Eisai and Roche; reimbursement for travel expenses from BMS. P.M. is supported by a Young Investigator Award by the Kidney Cancer Association and by a Department of Defense Kidney Cancer Concept Award. J.G. was a part of consulting in Guidepoint Global and AstraZeneca and advisory committee member of Jounce. M.T.C. was a member of advisory boards of/ received honoraria from Eisai, EMD Serono, Pfizer, Genentech and AstraZeneca; was a part of consulting in Apricity; participated in non-branded educational programs of BMS, Roche and Merck. A.J.Z. conducted research in Infinity Pharmaceuticals. P.G.C. received reimbursement for travel expenses from Millennium Pharmaceuticals and was a preceptor in OhioHealth. E.J. conducted research in Exelixis, Novartis, Pfizer and Peloton and received honoraria from ARMO, Eisai, Exelixis, Genentech, Ipsen, Novartis, Pfizer and Roche. R.J.M. was a part of consulting in Pfizer, Exelixis, Eisai, Genentech/Roche, Incyte, Merck and Novartis and received research funding to employer (MSK) for clinical trial support from BMS, Genentech/Roche, Eisai and Pfizer. P.S. has stock/ownership in Jounce, Neon, Constellation, Oncolytics, BioAtla, Forty-Seven, Apricity, Polaris, Marker Therapeutics, Codiak and ImaginAB; received honoraria from Constellation, Jounce, Kite Pharma, Neon, BioAtla, Pieris, Oncolytics, Merck, Forty-Seven, Polaris, Apricity, Marker Therapeutics, Codiak, ImaginAB and patents/royalty from Jounce, Merck and BMS. M.H.V. received commercial research grants from BMS, Genentech/Roche; received honoraria from Novartis; received travel/accommodation grants from Eisai, Novartis, Takeda; was a consultant/advisory board member of Alexion Pharmaceuticals, Bayer, Calithera Biosciences, Corvus Pharmaceuticals, Exelixis, Eisai, GlaxoSmithKline, Natera, Novartis and Pfizer. N.M.T. received grant/research support from BMS, Novartis and Exelixis; was a paid consultant for Oncorena, Exelixis and Nektar; received honoraria: Pfizer, Novartis, BMS, Exelixis, Nektar, Calithera Biosciences, Eisai and Ono Pharmaceutical. The other authors have nothing to declare. Funding Information: A.Y.S. received research funding to employer for clinical trial support from BMS, Eisai and EMD Serono; honoraria from Eisai and Roche; reimbursement for travel expenses from BMS. P.M. is supported by a Young Investigator Award by the Kidney Cancer Association and by a Department of Defense Kidney Cancer Concept Award. J.G. was a part of consulting in Guidepoint Global and AstraZeneca and advisory committee member of Jounce. M.T.C. was a member of advisory boards of/ received honoraria from Eisai, EMD Serono, Pfizer, Genentech and AstraZeneca; was a part of consulting in Apricity; participated in non-branded educational programs of BMS, Roche and Merck. A.J.Z. conducted research in Infinity Pharmaceuticals. P.G.C. received reimbursement for travel expenses from Millennium Pharmaceuticals and was a preceptor in OhioHealth. E.J. conducted research in Exelixis, Novartis, Pfizer and Peloton and received honoraria from ARMO, Eisai, Exelixis, Genentech, Ipsen, Novartis, Pfizer and Roche. R.J.M. was a part of consulting in Pfizer, Exelixis, Eisai, Genentech/Roche, Incyte, Merck and Novartis and received research funding to employer (MSK)for clinical trial support from BMS, Genentech/Roche, Eisai and Pfizer. P.S. has stock/ownership in Jounce, Neon, Constellation, Oncolytics, BioAtla, Forty-Seven, Apricity, Polaris, Marker Therapeutics, Codiak and ImaginAB; received honoraria from Constellation, Jounce, Kite Pharma, Neon, BioAtla, Pieris, Oncolytics, Merck, Forty-Seven, Polaris, Apricity, Marker Therapeutics, Codiak, ImaginAB and patents/royalty from Jounce, Merck and BMS. M.H.V. received commercial research grants from BMS, Genentech/Roche; received honoraria from Novartis; received travel/accommodation grants from Eisai, Novartis, Takeda; was a consultant/advisory board member of Alexion Pharmaceuticals, Bayer, Calithera Biosciences, Corvus Pharmaceuticals, Exelixis, Eisai, GlaxoSmithKline, Natera, Novartis and Pfizer. N.M.T. received grant/research support from BMS, Novartis and Exelixis; was a paid consultant for Oncorena, Exelixis and Nektar; received honoraria: Pfizer, Novartis, BMS, Exelixis, Nektar, Calithera Biosciences, Eisai and Ono Pharmaceutical. The other authors have nothing to declare. Publisher Copyright: {\textcopyright} 2019 Elsevier Ltd",
year = "2019",
month = jun,
doi = "10.1016/j.ejca.2019.04.003",
language = "English (US)",
volume = "114",
pages = "67--75",
journal = "European Journal of Cancer",
issn = "0959-8049",
publisher = "Elsevier Limited",
}