Impact of C-reactive protein flare-response on oncological outcomes in patients with metastatic renal cell carcinoma treated with nivolumab

Background The dynamic change in C-reactive protein (CRP) levels, CRP kinetics, is a prognostic factor for metastatic renal cell carcinoma (mRCC) in the tyrosine kinase inhibitor era. We investigated the impact of early CRP kinetics on the efficacy of nivolumab in patients with mRCC.Methods We perfo...

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Autores principales:	Toshiki Kijima, Shohei Fukuda, Kazutaka Saito, Yosuke Yasuda, Soichiro Yoshida, Minato Yokoyama, Junichiro Ishioka, Yoh Matsuoka, Yukio Kageyama, Yasuhisa Fujii
Formato:	article
Lenguaje:	EN
Publicado:	BMJ Publishing Group 2021
Materias:	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/f825a204d6ee4a078c4f34cf42d92aee
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spelling	oai:doaj.org-article:f825a204d6ee4a078c4f34cf42d92aee2021-11-16T04:00:05ZImpact of C-reactive protein flare-response on oncological outcomes in patients with metastatic renal cell carcinoma treated with nivolumab10.1136/jitc-2020-0015642051-1426https://doaj.org/article/f825a204d6ee4a078c4f34cf42d92aee2021-02-01T00:00:00Zhttps://jitc.bmj.com/content/9/2/e001564.fullhttps://doaj.org/toc/2051-1426Background The dynamic change in C-reactive protein (CRP) levels, CRP kinetics, is a prognostic factor for metastatic renal cell carcinoma (mRCC) in the tyrosine kinase inhibitor era. We investigated the impact of early CRP kinetics on the efficacy of nivolumab in patients with mRCC.Methods We performed a retrospective analysis of 42 mRCC patients who were treated with nivolumab as a second-line or later therapy between 2016 and 2019. All patients had received previous TKI therapy. Patients were divided into three groups based on their early CRP kinetics: CRP levels increased to more than double compared with baseline within 1 month after initiation of nivolumab (flare) and then decreased to a lower value than baseline within 3 months (CRP flare-responders); CRP levels decreased by ≥30% within 3 months without “flare” (CRP responders); and the remaining patients (non-CRP responders). The maximum tumor shrinkage, objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) were evaluated. The association of the early CRP kinetics and oncological outcomes was assessed.Results The median follow-up period was 8 months. The median baseline CRP level was 23 mg/L. CRP flare-responders, CRP responders, and non-CRP responders included 11 (26%), 15 (36%), and 16 (38%) patients, respectively. Thirteen patients (31%) died of mRCC. The maximum changes in target lesions from baseline of CRP flare-responder, CRP-responder, and non-CRP responder groups were −38%, −13%, and 16%, on average, respectively (p<0.001). ORRs of these three groups were 73%, 27%, and 6%, respectively (p<0.001). The median PFS values of each group were not reached, 12 months, and 2.4 months (p=0.005), and the median OS values were not reached, not reached, and 12 months (p=0.048). In a multivariate analysis, early CRP kinetics was a significant independent factor for objective response, PFS, and OS (p<0.001, p=0.004, and p=0.006, respectively).Conclusions CRP flare-response was associated with significant tumor shrinkage and improved survival outcomes in patients with mRCC who were treated with nivolumab. Early CRP kinetics could be useful for evaluating nivolumab treatment efficacy.Toshiki KijimaShohei FukudaKazutaka SaitoYosuke YasudaSoichiro YoshidaMinato YokoyamaJunichiro IshiokaYoh MatsuokaYukio KageyamaYasuhisa FujiiBMJ Publishing GrouparticleNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENJournal for ImmunoTherapy of Cancer, Vol 9, Iss 2 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Toshiki Kijima Shohei Fukuda Kazutaka Saito Yosuke Yasuda Soichiro Yoshida Minato Yokoyama Junichiro Ishioka Yoh Matsuoka Yukio Kageyama Yasuhisa Fujii Impact of C-reactive protein flare-response on oncological outcomes in patients with metastatic renal cell carcinoma treated with nivolumab
description	Background The dynamic change in C-reactive protein (CRP) levels, CRP kinetics, is a prognostic factor for metastatic renal cell carcinoma (mRCC) in the tyrosine kinase inhibitor era. We investigated the impact of early CRP kinetics on the efficacy of nivolumab in patients with mRCC.Methods We performed a retrospective analysis of 42 mRCC patients who were treated with nivolumab as a second-line or later therapy between 2016 and 2019. All patients had received previous TKI therapy. Patients were divided into three groups based on their early CRP kinetics: CRP levels increased to more than double compared with baseline within 1 month after initiation of nivolumab (flare) and then decreased to a lower value than baseline within 3 months (CRP flare-responders); CRP levels decreased by ≥30% within 3 months without “flare” (CRP responders); and the remaining patients (non-CRP responders). The maximum tumor shrinkage, objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) were evaluated. The association of the early CRP kinetics and oncological outcomes was assessed.Results The median follow-up period was 8 months. The median baseline CRP level was 23 mg/L. CRP flare-responders, CRP responders, and non-CRP responders included 11 (26%), 15 (36%), and 16 (38%) patients, respectively. Thirteen patients (31%) died of mRCC. The maximum changes in target lesions from baseline of CRP flare-responder, CRP-responder, and non-CRP responder groups were −38%, −13%, and 16%, on average, respectively (p<0.001). ORRs of these three groups were 73%, 27%, and 6%, respectively (p<0.001). The median PFS values of each group were not reached, 12 months, and 2.4 months (p=0.005), and the median OS values were not reached, not reached, and 12 months (p=0.048). In a multivariate analysis, early CRP kinetics was a significant independent factor for objective response, PFS, and OS (p<0.001, p=0.004, and p=0.006, respectively).Conclusions CRP flare-response was associated with significant tumor shrinkage and improved survival outcomes in patients with mRCC who were treated with nivolumab. Early CRP kinetics could be useful for evaluating nivolumab treatment efficacy.
format	article
author	Toshiki Kijima Shohei Fukuda Kazutaka Saito Yosuke Yasuda Soichiro Yoshida Minato Yokoyama Junichiro Ishioka Yoh Matsuoka Yukio Kageyama Yasuhisa Fujii
author_facet	Toshiki Kijima Shohei Fukuda Kazutaka Saito Yosuke Yasuda Soichiro Yoshida Minato Yokoyama Junichiro Ishioka Yoh Matsuoka Yukio Kageyama Yasuhisa Fujii
author_sort	Toshiki Kijima
title	Impact of C-reactive protein flare-response on oncological outcomes in patients with metastatic renal cell carcinoma treated with nivolumab
title_short	Impact of C-reactive protein flare-response on oncological outcomes in patients with metastatic renal cell carcinoma treated with nivolumab
title_full	Impact of C-reactive protein flare-response on oncological outcomes in patients with metastatic renal cell carcinoma treated with nivolumab
title_fullStr	Impact of C-reactive protein flare-response on oncological outcomes in patients with metastatic renal cell carcinoma treated with nivolumab
title_full_unstemmed	Impact of C-reactive protein flare-response on oncological outcomes in patients with metastatic renal cell carcinoma treated with nivolumab
title_sort	impact of c-reactive protein flare-response on oncological outcomes in patients with metastatic renal cell carcinoma treated with nivolumab
publisher	BMJ Publishing Group
publishDate	2021
url	https://doaj.org/article/f825a204d6ee4a078c4f34cf42d92aee
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Impact of C-reactive protein flare-response on oncological outcomes in patients with metastatic renal cell carcinoma treated with nivolumab

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