Abstract
BackgroundThere is an unmet need to determine factors predictive of clinical benefit, to guide therapeutic sequencing and selection in metastatic RCC (mRCC). We evaluated clinical factors such as the neutrophil lymphocyte ratio (NLR) and duration of prior anti-vascular endothelial growth factor (VEGF) inhibitors, as predictors of response rate, progression free survival (PFS) and overall survival (OS) in mRCC patients treated with immune checkpoint inhibitor (ICI).MethodsRegulatory approval was obtained. A single center retrospective chart review of mRCC patients at Karmanos Cancer Institute, treated with ICI based therapy (PD-1/PD-L1 inhibitors) was conducted. Data were collected on demographics, smoking status, prognostic scoring (Memorial Sloan Kettering and Heng criteria), NLR pretherapy, post 1 and 4 doses of ICI, and duration of prior anti-VEGF therapy ≥6 months or <6.Results42 patients were evaluated with median age of 61 years (range, 24-85). Pretherapy NLR < 3 and ≥3 was seen in 19 (45%) and 23 (55%) patients, respectively. 24 (57%) and 18 (43%) patients had prior anti-VEGF inhibitors for a duration of ≥6 months and <6 months, respectively. 12 (29%), 22 (52%) and 8 (19%) patients had favorable, intermediate and poor risk disease based on Heng criteria, respectively. Multivariable analysis showed pretherapy NLR ≥3 was predictive of shorter PFS and OS when treated with ICI with median 3.08 months and 13.50 months, respectively, versus 15.57 months and not reached for NLR < 3 (adjusted p-values =0.003 and 0.025, respectively). Prior anti-VEGF therapy <6 months was predictive of increased likelihood of benefit from ICI therapies (adjusted p = 0.028). The median PFS was 3.72 months and 14.33 months, respectively, in cases with prior anti-VEGF therapy for ≥6 months and <6 months.ConclusionPretherapy NLR <3 and duration of prior anti-VEGF therapy of <6 months, are independent statistically significant predictors of longer PFS and OS with ICI therapy in mRCC. Validation is required in a larger sample size with multi-institutional collaboration.
Highlights
There is an unmet need to determine factors predictive of clinical benefit, to guide therapeutic sequencing and selection in metastatic RCC
We evaluated the potential role of clinical factors such as neutrophil lymphocyte ratio (NLR) and duration of benefit from prior anti-vascular endothelial growth factor (VEGF) inhibitors, as predictors of response rates, progression free survival (PFS) and overall survival (OS) in metastatic RCC (mRCC) patients treated with immune checkpoint inhibitor(ICI)
Our study found that pretherapy NLR
Summary
There is an unmet need to determine factors predictive of clinical benefit, to guide therapeutic sequencing and selection in metastatic RCC (mRCC). Immune checkpoint inhibitor (ICI) therapy has a unique mechanism of action of restoring T cell mediated immune response by blocking PD-1 and PD L1 interaction [1] This therapy has recently entered the therapeutic realm of metastatic renal cell cancer (mRCC). In a parallel randomized trial, cabozantinib demonstrated both progression free survival and OS benefit over everolimus and received FDA approval [4]. There is an unmet need for utilization of biomarkers to help guide therapeutic selection in mRCC This will clearly aid in optimization of existing therapies and prevent exposure to adverse effects of unnecessary therapies with minimal likelihood of clinical benefit. Predictive biomarkers will help streamline the cost of therapies in RCC
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
