Presentation Authors: Shohei Fukuda*, Kazutaka Saito, Yosuke Yasuda, Tokyo, Japan, Takahiko Soma, Saitama, Japan, Masahiro Toide, Hiroshi Fukushima, Shingo Moriyama, Sho Uehara, Tokyo, Japan, Naotaka Fukui, Saitama, Japan, Toshiki Kijima, Soichiro Yoshida, Minato Yokoyama, Junichiro Ishioka, Yoh Matsuoka, Tokyo, Japan, Yukio Kageyama, Saitama, Japan, Yasuhisa Fujii, Tokyo, Japan
Introduction: C-reactive protein (CRP), a representative systemic inflammatory response, has been shown to be a potential biomarker for renal cell carcinoma (RCC). The dynamic change of CRP levels, CRP kinetics, is a predictive factor for survival of patients with metastatic RCC (mRCC) in the tyrosine kinase inhibitor (TKI) era. In this study, we investigated the impact of the early CRP kinetics on the efficacy of nivolumab in patients with mRCC.
Methods: A total of 32 patients (25 males and 7 females) were treated with nivolumab for mRCC from 2016 to 2018 at our institutions. Patients were divided into three groups according to their early CRP kinetics (Fig.1): patients whose CRP levels had increased to more than double from baseline within 1 month after initiation of nivolumab (flare) and then decreased to a lower value than baseline within 3 months (CRP flare-responder), patients whose CRP levels decreased by â‰¥30% from baseline within 3 months without &[Prime]flare&[Prime] (CRP responder), and the remaining patients (non-CRP responder). Maximum tumor shrinkage and objective response rate were evaluated based on the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. The association of the early CRP kinetics and radiological responses to nivolumab was assessed.
Results: The median follow up period and number of administration cycles were 5 months (range 1-18) and 8 cycles (1-28), respectively. The median baseline CRP level was 30 mg/L (0.2-169). Among all patients, CRP flare-responders, CRP responders and non-CRP responders were 8 (25%), 12 (37.5%) and 12 (37.5%) patients, respectively. Nine patients (28%) died of mRCC. During the follow-up period, 6 (19%), 19 (59%) and 7 (22%) patients experienced partial response, stable disease and progressive disease, respectively. The maximum change in target lesion from baseline of CRP flare-responder, CRP-responder and non-CRP responder group were -35%, -8% and +19% on average, respectively (p < 0.001) (Fig. 2). Objective response rates of these three groups were 63%, 8% and 0%, respectively (p=0.001).
Conclusions: Early flare-response of CRP is associated with tumor shrinkage in patients with mRCC treated with nivolumab. The early CRP kinetics could be useful in evaluating the treatment efficacy of nivolumab.