Adjuvant sunitinib (SU) in patients (pts) with high risk renal cell carcinoma (RCC): Safety and therapy management in S-TRAC trial

Biomarkers to guide treatment in metastatic renal cell carcinoma (mRCC) are lacking. Existing literature shows that neutrophil-to-lymphocyte ratio (NLR) predicts prognosis for mRCC patients receiving targeted therapy. We aimed to investigate the association between pretreatment NLR and prediction of outcome in patients with mRCC receiving nivolumab.

We performed a retrospective chart review of 38 patients with mRCC treated with nivolumab as standard of care between 2015 – 2016 at Winship Cancer Institute of Emory University. NLR was determined from complete blood count collected prior to starting treatment and imaging was performed to assess progression. We defined clinical benefit as complete response (CR) or partial response (PR) or stable disease (SD) of greater than 4 months. Progression-free survival (PFS) was defined as time from nivolumab initiation to date of progression, hospice referral, or death from any cause. Overall survival (OS) was defined as time from nivolumab initiation to death or hospice referral. The NLR cutoff value of 5.5 was determined by log rank test, and the univariate association with OS or PFS was assessed by Cox proportional hazard model and Kaplan-Meier method.

The 38 patients had a median age of 68.5 years; 29 (76%) were men and 9 (24%) were women. Within the cohort, tumor histology includes 20 (53%) non-clear cell and 18 (47%) clear cell. The majority of patients (45%) had KPS score of 80-100. MSKCC score within the cohort showed 4 (10%) patients with good risk, 20 (53%) patients with intermediate risk, and 14 (37%) with poor risk. Response was evaluable for 32 patients; the other six patients did not complete two cycles (8 weeks) of treatment. One patient experienced CR, one patient had PR, and 15 patients (40%) experienced SD. Among those 15 patients with SD, 12 patients (80%) had stable disease for greater than 4 months. In our cohort, a total of 17 patients (53%) had clinical benefit after nivolumab treatment. The PFS and OS for all patients at 12 months was 54% and 69%, respectively. The median PFS was 2.6 months in the high NLR group but not reached in the low NLR group (Figure 1A). Low NLR was strongly associated with increased PFS with hazard ratio HR of 0.26 (95% CI 0.09-0.74; p=0.012). The median OS was 2.7 months in the high NLR group but not reached in the low NLR group (Figure 1B). Again, low NLR was significantly associated with a prolonged OS with a hazard ratio of 0.06 (95% CI 0.01-0.049; p=0.009).

Pre-treatment NLR less than or equal to 5.5 is associated with superior PFS and OS. NLR can be used as a biomarker for prognosis in patients with mRCC and should be further validated in larger cohorts and in prospective studies.