Efficacy and Safety of Nivolumab and Ipilimumab for Advanced or Metastatic Renal Cell Carcinoma: A Multicenter Retrospective Cohort Study

Abstract

We conducted a multicenter, retrospective study to evaluate the efficacy and safety of combination nivolumab plus ipilimumab (NIVO+IPI) in 35 patients with advanced or metastatic renal cell carcinoma (mRCC). In this study, we focused on patients who received NIVO+IPI and were stratified into intermediate- or poor-risk disease according to the International Metastatic Renal Cell Carcinoma Database Consortium model at five institutions in Japan. The primary endpoint was overall survival (OS). Secondary endpoints were disease control rate (DCR), best overall response (BOR), objective response rate (ORR), and progression-free survival (PFS). In addition, we evaluated the role of inflammatory cell ratios, namely neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), as predictive biomarkers in patients with mRCC. The median follow-up period was 1 year, and the 1-year OS rate was 95.8%. The ORR and DCR were 34.3% and 80.0%, respectively. According to BOR, four patients (11.4%) achieved complete response. According to NLR stratification, the 1-year PFS rates were 82.6% and 23.7% when the NLR was ≤4.6 and >4.6, respectively (p = 0.04). Based on PLR stratification, the 1-year PFS rates were 81.7% and 34.3% when the PLR was ≤188.1 and >188.1, respectively (p = 0.033). Although 71.4% of the patients experienced treatment-related adverse events (TRAEs) with NIVO+IPI, only four patients discontinued NIVO+IPI due to grade 3/4 TRAEs. Patients treated with NIVO+IPI as a first-line therapy for advanced or mRCC achieved relatively better oncological outcomes. Therefore, NIVO+IPI may have potential advantages and may lead to a treatment effect compared to those receiving targeted therapies. In addition, PLR >188.1 may be a useful predictive marker for mRCC patients who received NIVO+IPI.

Keywords: immune-oncology treatments; ipilimumab; metastatic renal cell carcinoma; nivolumab; platelet-to-lymphocyte ratio.

Figure 1

Kaplan–Meier estimates of overall survival (OS) (A) and progression-free survival (PFS) (B). The OS at 6, 12, and 18 months after nivolumab plus ipilimumab initiation was 100%, 95.8%, and 87.1%, respectively, while the PFS was 78.6%, 56.2%, and 56.2%, respectively.

Figure 2

Kaplan–Meier estimates of progression-free survival (PFS) according to neutrophil-to-lymphocyte ratio (NLR) stratified by a cut-off value of 4.6 (A) and to platelet-to-lymphocyte ratio (PLR) stratified by a cut-off value of 188.1 (B). According to NLR stratification, the 1-year PFS rates were 82.6% when NLR ≤ 4.6 and 23.7% when NLR > 4.6 (p = 0.04; Figure 2A). Based on PLR stratification, the 1-year PFS rates were 81.7% when PLR ≤ 188.1 and 34.3% when PLR > 188.1 (p = 0.033; Figure 2B).