Original Study
Modified Glasgow Prognostic Score as a Predictor of Prognosis in Metastatic Renal Cell Carcinoma Treated With Nivolumab

https://doi.org/10.1016/j.clgc.2020.10.007Get rights and content

Abstract

Background

The modified Glasgow prognostic score (mGPS), which incorporates serum albumin and C-reactive protein levels, reflects systemic inflammation and nutritional status. In this study, we evaluate the role of mGPS as a predictor of prognosis in metastatic renal cell carcinoma treated with nivolumab.

Patients and Methods

Forty-five consecutive patients with metastatic renal cell carcinoma receiving nivolumab therapy after tyrosine kinase inhibitor therapy between September 2013 and August 2019 at our institution were retrospectively analyzed. The prognostic factors associated with overall survival were statistically analyzed.

Results

The median follow-up period was 26.4 months. The median progression-free survival and 1- and 3-year progression-free survival rates were 11.6 months, 48.9%, and 17.1%, respectively. The median overall survival and 1- and 3-year overall survival rates were not reached, 88.7%, and 62.3%, respectively. In multivariate analysis, mGPS at the time of nivolumab administration (P < .0001; hazard ratio [HR], 95.7; P = .0004 [Score 1 vs. 0]; HR, 98.9; P = .0002 [Score 2 vs. 0]; and HR, 1.03; P = .971 [Score 2 vs. 1]) was extracted as the strongest predictor for overall survival followed by duration from diagnosis to treatment (P = .0001), lactate dehydrogenase (P = .0005), and lymphocyte count (P = .021). Overall survival curves were distinctly separated between mGPS Score 0 and mGPS Score 1 + 2, with median overall survival periods being not reached and 32.4 months, respectively (P = .0004).

Conclusions: mGPS was the strongest significant prognostic biomarker in patients with metastatic renal cell carcinoma treated with nivolumab. This simple classification could be useful in clinical practice.

Introduction

Nivolumab (Optivo, Ono/Bristol-Myers Squibb), a fully human IgG4 programmed death 1 antibody, is a novel targeted agent that has been available in clinical practice for the treatment of metastatic renal cell carcinoma (mRCC) since 20161 and is now being rapidly adopted in Japan. Its promising anti-tumor efficacy and manageable safety profile were demonstrated in the phase III Checkmate 025 trial.1 We have previously reported on its efficacy (objective response rate, 44%) and safety profile (serious adverse events, 10% and no treatment-related deaths) in Japanese patients with mRCC.2

In real-world clinical practice, it is important to identify biomarkers that enable us to predict the response to nivolumab, as this improves our capacity for stratification of patients with mRCC. Currently, some reports have suggested that systemic inflammation is associated with disease development and progression.3,4 Inflammation biomarkers such as C-reactive protein (CRP), neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and lymphocyte-to-monocyte ratio could shed light on the prognosis of patients with mRCC receiving nivolumab therapy.5,6 The modified Glasgow prognostic score (mGPS), a scoring system incorporating serum albumin and CRP, has been reported to reflect systemic inflammation and nutritional status and is considered to be a prognostic factor for several cancers treated through surgery or chemotherapy, including bladder cancer, upper tract urothelial carcinoma, pancreatic cancer, colorectal cancer, and RCC.7, 8, 9, 10 In patients with mRCC receiving nivolumab therapy, however, its prognostic value remains unclear. To fill this gap, we evaluated the prognostic role of mGPS in patients with mRCC treated with nivolumab.

Section snippets

Study Population

The clinical and laboratory data from 45 consecutive patients with mRCC who had previously been treated with tyrosine kinase inhibitors (TKIs) before starting treatment with nivolumab between September 2013 and August 2019 at our institution were retrospectively investigated. Two patients from this cohort had been enrolled in clinical trials. Forty-two patients had target lesions at the initiation of nivolumab. This study was approved by the Institutional Review Board at the Cancer Institute

Patient Characteristics

The median follow-up period was 26.4 months (interquartile range, 16.9-30.3 months) after initiation of nivolumab. Patient characteristics are described in Table 1. Ten (22%) patients died as a result of disease progression, and the remaining 35 (78%) patients survived; among these patients, 34 (97%) and 1 (3%) were alive at least 1 year and still within 1 year after initiation of nivolumab. Nivolumab was administered as a second-line therapy in 31 patients, a third-line therapy in 11 patients,

Discussion

We previously demonstrated the therapeutic outcomes and safety profiles of nivolumab after TKI in Japanese patients with mRCC in real-world clinical practice.2 In this study, we reported that mGPS was the most significant prognostic factor for OS in patients with mRCC treated with nivolumab. To the best of our knowledge, this is the first report to show that mGPS is an effective prognostic biomarker for the outcome of nivolumab therapy for mRCC. Although the efficacy of nivolumab therapy for

Disclosure

T. Yuasa has received remuneration for lectures from Astellas, Sanofi Japan, Pfizer Japan, Novartis Pharma Japan, Ono Pharma, Bristol-Myers Squibb Japan, Janssen Pharmaceutical K.K. Japan, MSD Japan, and Daiichi-Sankyo. The remaining authors have stated that they have no conflicts of interest.

CRediT authorship contribution statement

Ryo Fujiwara: Conceptualization, Data curation, Formal analysis, Writing - original draft, Writing - review & editing. Kosuke Takemura: Data curation, Formal analysis, Writing - review & editing. Motohiro Fujiwara: Supervision, Writing - review & editing. Takeshi Yuasa: Conceptualization, Writing - review & editing. Shotaro Yasuoka: Writing - review & editing. Yoshinobu Komai: Writing - review & editing. Noboru Numao: Writing - review & editing. Shinya Yamamoto: Writing - review & editing.

Acknowledgments

This work was partly supported by the Smoking Research Foundation and JSPS KAKENHI Grant Number 16K11035 (T.Y.).

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