scholarly journals Bone metastases affect prognosis but not effectiveness of third-line targeted therapies in patients with metastatic renal cell carcinoma

2015 ◽  
Vol 9 (7-8) ◽  
pp. 263 ◽  
Author(s):  
Roberto Iacovelli ◽  
Daniele Santini ◽  
Mimma Rizzo ◽  
Alessandra Felici ◽  
Matteo Santoni ◽  
...  

Introduction: Treatment of metastatic renal cell carcinoma (mRCC) has improved with the use of targeted therapies, but bone metastases continue to be negative prognostic factor.Methods: Patients with mRCC treated with everolimus (EV) or sorafenib (SO) after two previous lines of targeted therapies were included in the analysis. Overall survival (OS) and progressionfree survival (PFS) were assessed based on the presence of bone metastases and type of therapy; they were also adjusted based on prognostic criteria.Results: Of the 233 patients with mRCC, 76 had bone metastases. Of the 233 patients, EV and SO were administered in 143 and 90 patients, respectively. Median OS was 10.4 months in patients with BMs and 17.4 months in patients without bone metastases (p = 0.002). EV decreased the risk of death by 18% compared to SO (adjusted hazard ratio [HR] 0.82, 95% confidence interval [CI] 0.74–0.91; p < 0.001), with comparable effects in patients with or without bone metastases. In the same manner, EV decreased the risk of progression by 12% compared to SO (adjusted HR 0.88, 95% CI 0.82–0.96; p = 0.002), but this difference was not significant in patients without bone metastases. The major limitations of the study are its retrospective nature, the heterogeneity of the methods to detect bone metastases, and the lack of data about patients treated with bisphosphonates.Conclusions: The relative benefit of targeted therapies in mRCC is not affected by the presence of bone metastases, but patients without bone metastases have longer response to therapy and overall survival.

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A29-A29
Author(s):  
Arnab Basu ◽  
Yash Suri ◽  
Lakshminarayan Nandagopal ◽  
Mollie Deshazo ◽  
Lyse Norian ◽  
...  

BackgroundElevated baseline neutrophil lymphocyte ratios (NLR) are now well established as a poor predictor of survival in renal cell carcinoma (RCC) and other cancers. Platelet Lymphocyte Ratios (PLR) have also recently shown similar effects. Despite these findings, the practical use of these ratios is still somewhat limited. We have previously shown that higher NLRs may be associated with increased concentrations of myeloid derived suppressor cells (MDSC). We hypothesized that increases in NLR or PLR (NLR/PLR failure) at 2 months while on immunotherapy could be a predictor of eventual treatment failure and overall survival.MethodsWe analyzed patients who received nivolumab therapy for RCC at our institution from 3/2016 to 6/2019. Patients with complete data on NLR and PLR at time = 0 and +2 months and those who had accurate response and overall survival information available were selected (n = 37). Information on comorbidities, previous therapy, demographics were collected for adjusted analysis. NLR failure was defined as an increase of 3 or more compared to baseline NLR. Cox proportional hazard models were used to analyze the risk of progression and death with NLR/PLR failure at 2 months (± 2 weeks). Kaplan Meier graphs were constructed to trace survival functions for PFS and OS by NLRResultsNLR failure was associated with a statistically significant increase in the risk of progression on nivolumab therapy (HR 4.26, 95% CI [1.47–12.3], p = 0.007), in an adjusted cox regression model that included baseline NLR. In this adjusted model, the value of baseline NLR to predict treatment failure was non-significant (HR 1.01, p – 0.69). Similarly, NLR failure increased the risk of death (HR 3.83 95% CI [1.23–11.9], p = 0.02), with a similar non-significant contribution of baseline NLR (HR 1.06, p = 0.06). NLR failure predicted PFS less than 6 months with 90% positive predictive value (9/10) and a 48% (12/25) negative predictive value, and survival less than 1 year with a 56% negative predictive value and 100% positive predictive value (10/10). PLR changes failed to show any association with PFS (HR 0.99, p = 0.93) or OS (HR 1.00, p = 0.93).ConclusionsAn increase in NLR of 3 or more at 2 months of therapy with nivolumab appears to predict for impending treatment failure and increasing risk of death with a high positive predictive value. NLR failure if validated in larger studies could be useful in treatment managementEthics ApprovalThe study was approved by UAB Comprehensive Cancer Centers Ethics Board


Cancers ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 1000 ◽  
Author(s):  
Chen ◽  
Hernandez-Meza ◽  
Agrawal ◽  
Zhang ◽  
Xie ◽  
...  

With 15 drugs currently approved for the treatment of metastatic renal cell carcinoma (mRCC) and even more combination regimens with immunotherapy on the horizon, there remains a distinct lack of molecular biomarkers for therapeutic efficacy. Our study reports on real-world clinical outcomes of mRCC patients from a tertiary academic medical center treated with empirically selected standard-of-care therapy. We utilized the Stanford Renal Cell Carcinoma Database (RCCD) to report on various outcome measures, including overall survival (OS) and the median number of lines of targeted therapies received from the time of metastatic diagnosis. We found that most metastatic patients did not survive long enough to attempt even half of the available targeted therapies. We also noted that patients who failed to receive a clinical benefit within the first two lines of therapy could still go on to experience clinical benefit in later lines of therapy. The term, “clinical benefit” was assigned to a line of therapy if a patient remained on drug treatment for three months or longer. Moreover, patients with clinical benefit in at least one line of therapy experienced significantly longer OS compared to those who did not have clinical benefit in at least one line of therapy. Developing biomarkers that identify patients who will receive clinical benefit in individual lines of therapy is one potential strategy for achieving rational drug sequencing in mRCC.


2013 ◽  
Vol 39 (4) ◽  
pp. 388-401 ◽  
Author(s):  
Ahmed Alasker ◽  
Malek Meskawi ◽  
Maxine Sun ◽  
Salima Ismail ◽  
Nawar Hanna ◽  
...  

2011 ◽  
Vol 6 (3) ◽  
pp. 189-198 ◽  
Author(s):  
Marc R. Matrana ◽  
Bradley Atkinson ◽  
Eric Jonasch ◽  
Nizar M. Tannir

Sign in / Sign up

Export Citation Format

Share Document