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C-reactive protein at 1 month after treatment of nivolumab as a predictive marker of efficacy in advanced renal cell carcinoma.
- Source :
-
Cancer chemotherapy and pharmacology [Cancer Chemother Pharmacol] 2020 Jul; Vol. 86 (1), pp. 75-85. Date of Electronic Publication: 2020 Jun 14. - Publication Year :
- 2020
-
Abstract
- Purpose: Nivolumab is part of the standard therapy for mRCC. Although deep and long-lasting responses are seen in some patients, the benefit of treatment is limited to some patients and the majority of patients will experience disease progression. PD-L1 is still under evaluation as a predictive biomarker and there is an urgent need to establish biomarkers for the treatment of nivolumab. Here, we investigate C-reactive protein (CRP) at 1 month after treatment of nivolumab as a target to predict the response of patients with metastatic renal cell carcinoma (mRCC) to nivolumab.<br />Methods: After approval of the study by our institutional review board, 64 patients with mRCC who underwent nivolumab treatment at Kanagawa Cancer Center and Yokohama City University Hospital were enrolled. The patient characteristics, blood examination data at start of nivolumab treatment and 1 month after treatment, response to treatment and progression-free survival (PFS) were evaluated. Tumour responses were assessed according to both the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and the immune RECIST (iRECIST) criteria. Moreover, in 12 patients who agreed to an additional blood examination, several serum inflammatory factors were investigated and their correlation with CRP level was examined.<br />Results: The median follow-up was 8.3 months (range 0.2-29.8 months). The median PFS period was 4.5 months and the median immune-PFS (iPFS) period was 5.3 months. RECIST 1.1 criteria underestimated the benefits of nivolumab in four (6.4%) cases. Multivariate analyses showed that an Eastern Cooperative Oncology Group performance status (≥ 2) at start of treatment and CRP level at 1 month after treatment (≥ 1.5 mg/dL) were independent risk factors for a poor iPFS of nivolumab. The CRP level at baseline was not an independent prognostic factor for iPFS. When compared with the responder group (iCR + iPR + iSD), the non-responder group (iPD) had a significantly higher CRP levels at 1 month after treatment (p < 0.001). In the responder group, there was significant decrease in the CRP level after nivolumab treatment when compared with the baseline (p = 0.002), whereas there was a significant increase in the non-responder group (p = 0.019). Even patients with high baseline CRP (≥ 1.5 mg/dL) obtained good iPFS if CRP was decreased (< 1.5 mg/dL) 1 month after treatment. In addition, the classification of Glasgow prognostic score (GPS), which is a cumulative prognostic score based on CRP and albumin, was a significant predictor for iPFS. A strong correlation (|r| > 0.7) with CRP level at 1 month after treatment was seen for sCD163, IL-34, MMP-1, MMP-2, osteopontin, sTNF-R1 and sTNF-R2. Of these, MMP-1 and MMP-2 were not correlated at baseline.<br />Conclusion: Our results indicated that the CRP level at 1 month after treatment with nivolumab appears to be a promising predictive biomarker for response to nivolumab treatment in patients with mRCC. It is clinically useful to be able to predict the effect within a short period. Further prospective trials are needed to prove these preliminary findings.
- Subjects :
- Adult
Aged
Aged, 80 and over
Biomarkers, Pharmacological blood
Biomarkers, Tumor blood
Carcinoma, Renal Cell blood
Carcinoma, Renal Cell mortality
Carcinoma, Renal Cell pathology
Female
Humans
Inflammation metabolism
Kidney Neoplasms blood
Kidney Neoplasms mortality
Kidney Neoplasms pathology
Male
Middle Aged
ROC Curve
Treatment Outcome
Antineoplastic Agents, Immunological therapeutic use
C-Reactive Protein analysis
Carcinoma, Renal Cell drug therapy
Kidney Neoplasms drug therapy
Nivolumab therapeutic use
Subjects
Details
- Language :
- English
- ISSN :
- 1432-0843
- Volume :
- 86
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Cancer chemotherapy and pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 32537714
- Full Text :
- https://doi.org/10.1007/s00280-020-04088-y