Patterns, predictors and subsequent outcomes of disease progression in metastatic renal cell carcinoma patients treated with nivolumab

Abstract

BackgroundNivolumab is approved for the treatment of refractory metastatic renal cell carcinoma. Patterns and predictors of progressive disease (PD) on nivolumab, and outcomes in such patients are lacking.MethodsA retrospective analysis of patients (pts) with metastatic clear cell renal cell carcinoma (ccRCC) who received nivolumab at Cleveland Clinic (2015–2017) was performed. PD was defined per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 or clinical progression as per treating physician. Univariate analyses (UVA) and multivariate analyses (MVA) were used to identify clinical and laboratory markers as potential predictors of progression-free survival (PFS).ResultsNinety patients with mean age of 65, 74% men, and 83% good or intermediate International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk group were included. Median number of prior systemic treatments was 2 (range, 1–6). Median overall survival (OS) and PFS were 15.8 and 4.4 months, respectively. Fifty-seven patients (63%) had PD and 44% of patients with radiographic PD had new organ sites of metastases with brain (8/23, 35%) being the most common. Twelve patients received treatment beyond progression (TBP), and among 6 patients with available data, 3 (50%) had any tumor shrinkage (2 pts. with 17% shrinkage, one pt. with 29% shrinkage). Of 57 patients with PD, 28 patients (49%) were able to initiate subsequent treatment, mainly with axitinib and cabozantinib, while 40% of patients were transitioned to hospice after PD. In MVA, a higher baseline Neutrophil-to-Lymphocyte ratio (NLR) (HR, 1.86; 95% CI, 1.05–3.29; p = 0.033) was associated with an increased risk of progression, whereas higher (> 0.1 k/uL) baseline eosinophil count was associated with a lower risk of progression (HR, 0.54; 95% CI, 0.30–0.98; p = 0.042).ConclusionBrain was the most common site of PD in patients treated with nivolumab, and only half of patients progressing on nivolumab were able to initiate subsequent treatment. The risk of PD increased with a higher baseline NLR and reduced with a higher baseline eosinophil count.Electronic supplementary materialThe online version of this article (10.1186/s40425-018-0425-8) contains supplementary material, which is available to authorized users.

Newly developing brain metastases during nivolumab therapy for metastatic renal cell carcinoma: A case series in two Japanese institutions

“…In our case series, the brain was the most common metastatic organ in patients with new lesion appearance, supporting the finding of the previous study . In contrast, the incidence of new BMs has ranged from 3 to 9.7% in targeted therapy .…”

“…Recently, a remarkably high incidence of new BMs during nivolumab therapy for mRCC was reported . In that study, the brain was the most common metastatic organ in patients with new lesion appearance during nivolumab therapy (8/23, 35%), suggesting that the pattern of PD might be different in nivolumab from that in molecular‐targeted therapy.…”

Current status of prognostic factors in patients with metastatic renal cell carcinoma

“…Although there are few reports of prognostic factors for mRCC treated with ICIs, several studies have shown the association of some inflammatory markers with the prognosis of patients with various malignant diseases treated with ICIs (Table 3). [97][98][99][100][101][102][103][104][105][106] These reports indicate that the parameters related to inflammation might also have some prognostic impact on patients with mRCC treated with ICIs. Further study is expected to clarify the link between the mechanism of inflammation and the effects of ICIs, and to identify the markers related to inflammation to predict or evaluate the effects of ICIs.…”

“…Although there are few reports of prognostic factors for mRCC treated with ICIs, several studies have shown the association of some inflammatory markers with the prognosis of patients with various malignant diseases treated with ICIs (Table ) . These reports indicate that the parameters related to inflammation might also have some prognostic impact on patients with mRCC treated with ICIs.…”

High neutrophil, low lymphocyte and hemoglobin unfavorably impact survival in non-small cell lung cancer patients with brain metastases

“…The potential cause of these differences remains unclear, the determination and the best cut-off values of neutrophil, lymphocyte and hemoglobin should enroll in further randomized controlled trials to con rm their relevance in the incidence of BM and prognosis, which may help build a easy-to-calculate laboratory score for BM from NSCLC. Additionally, previous reports indicated that the serum markers such as peripheral blood cell counts can be used as a predictor for response to immunotherapy (31). Therefore, the in-depth study about prognostic values of neutrophil, lymphocyte and hemoglobin will help us to further understand the immune mechanism of NSCLC BM, and ultimately help us to make better clinical decisions in circumstances such as facing moderate-tosevere irAEs and distinguishing tumor ares (or pseudoprogressions) from true progressions.…”