Outcomes of patients with metastatic clear-cell renal cell carcinoma treated with second-line VEGFR-TKI after first-line immune checkpoint inhibitors Journal Article

Authors: Shah, A. Y.; Kotecha, R. R.; Lemke, E. A.; Chandramohan, A.; Chaim, J. L.; Msaouel, P.; Xiao, L.; Gao, J.; Campbell, M. T.; Zurita, A. J.; Wang, J.; Corn, P. G.; Jonasch, E.; Motzer, R. J.; Sharma, P.; Voss, M. H.; Tannir, N. M.
Article 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. © 2019 Elsevier Ltd
Keywords: adult; cancer survival; treatment response; aged; survival rate; major clinical study; overall survival; fatigue; bevacizumab; sunitinib; drug dose reduction; drug safety; drug withdrawal; gastrointestinal hemorrhage; monotherapy; treatment duration; cancer patient; follow up; anorexia; ipilimumab; metastasis; progression free survival; retrospective study; renal cell carcinoma; protein tyrosine kinase inhibitor; rash; immunotherapy; pazopanib; axitinib; clear cell renal cell carcinoma; rcc; hypertransaminasemia; body weight loss; immune checkpoint inhibitor; vegfr-tki; cabozantinib; body weight disorder; nivolumab; human; male; female; priority journal; article; ccrcc; atezolizumab; antineoplastic monoclonal antibody; immunotherapy refractory; metastatic kidney cancer; therapy sequence; aortic dissection
Journal Title: European Journal of Cancer
Volume: 114
ISSN: 0959-8049
Publisher: Elsevier Inc.  
Date Published: 2019-06-01
Start Page: 67
End Page: 75
Language: English
DOI: 10.1016/j.ejca.2019.04.003
PUBMED: 31075726
PROVIDER: scopus
PMCID: PMC7537491
Notes: Source: Scopus
Citation Impact
MSK Authors
  1. Joshua Chaim
    31 Chaim
  2. Robert Motzer
    1033 Motzer
  3. Martin Henner Voss
    212 Voss
  4. Ritesh Rajesh Kotecha
    26 Kotecha