Body Mass Index, Sarcopenia and Their Variations in Predicting Outcomes for Patients Treated with Nivolumab for Metastatic Renal Cell Carcinoma

Oncology ◽  
2021 ◽  
Author(s):  
Tressie Herrmann ◽  
Cécile Mione ◽  
Pierre-François Montoriol ◽  
Ioana Molnar ◽  
Angeline Ginzac ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Weight Gain ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Checkpoint Inhibitors ◽  
Predictive Markers ◽  
Skeletal Muscle Index ◽  
Weight Variation ◽  
The Impact

Introduction : The advent of immune checkpoint inhibitors (ICI) such as nivolumab has enabled outcomes for metastatic renal cell carcinoma (mRCC) to be improved. Although, only around 25% of patients respond to these therapies without being able to formally identify them. Datas on relevant predictive markers are still laking. The obesity paradox has been shown as a relevant prognostic marker in mRCC with better outcomes for obese patients. Nevertheless, the impact of weight variation and the presence of sarcopenia during ICI is not known for now. Methods : In a retrospective study, weight and its variations were collected at first day of ICI and at 6 weeks of treatment. Scanographic imagery was used to define the skeletal muscle index (SMI) as a reflect of sarcopenia. The impact of these parameters as predictive and prognostic factors for mRCC with nivolumab was evaluated. Results : A higher BMI at baseline was significantly associated with response at the first scan (p=0.036). Longer OS was observed for patients with a weight gain compared to the group with weight loss (p=0.00028). Median OS for sarcopenic patients was 17.2 months, and 31.6 months for the non-sarcopenic group of patients, but there was no statistical difference. Conclusion : This trial showed that a higher BMI and weight gain during nivolumab treatment were good predictive markers for outcomes in mRCC with nivolumab. Sarcopenia and variations in SMI could thus be of interest, but further studies are required.

Impact of antibiotics on outcome in patients with metastatic renal cell carcinoma treated with immune checkpoint inhibitors.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 462-462 ◽  
Author(s):  
Lisa Derosa ◽  
Bertrand Routy ◽  
David Enot ◽  
Giulia Baciarello ◽  
Christophe Massard ◽  
...  
Keyword(s):  
Risk Factors ◽  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Immune Checkpoint ◽  
Renal Cell ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Risk Groups ◽  
The Impact

462 Background: Preclinical data demonstrated that microbiota modulates activity of immune checkpoint inhibitors (ICB) and broad-spectrum antibiotics (ATB) damper their efficacy. However, the impact of ATB in patients (pts) treated with ICB remains unknown. Our study evaluates the effect of ATB use in metastatic renal cell carcinoma (mRCC) pts treated with ICB. Methods: We conducted a retrospective analysis of mRCC pts treated in prospective trials at Gustave Roussy with PD1/PD-L1 inhibitors alone or in combination. ATB (+)/(-) group were defined as pts treated or not with ATB at baseline (up to 1 month prior to the 1st injection of ICB). Progression-Free survival (PFS), Objective Response Rate (ORR), and Overall Survival (OS) were compared in each group (ATB (+) vs ATB (-)). Statistical analyses were performed using Kaplan-Meier method and Cox regression adjusted for risk factors. Results: We enrolled 80 mRCC pts treated with anti-PD-1/PD-L1 monotherapy (n=67), anti-PD-1 plus CTLA-4 (n=10) or anti-PD-L1 plus bevacizumab (n=3) with available data on ATB. Majority of pts were male (65%), clear-cell histology (88%), and had prior nephrectomy (80%). With regard to IMDC risk groups, 21%, 57%, and 22% had favorable, intermediate, and poor-risk disease, respectively. Sixteen (20%) pts belonged to the ATB (+) group (mostly receiving beta-lactamases and fluoroquinolones). ATB (+) had decreased PFS compared to ATB (-), 2.3 vs. 8.1 months, p<0.001. This statistical association was maintained after multivariate analysis adjusted for age, gender, IMDC risk groups, tumour burden and proton pomp inhibitors. In addition, ORR was lower in ATB (+) compared with ATB (-) (p<0.002). Even though it is too early to conclude on OS (median follow-up <6 months), there was already a negative trend driven in ATB (+). Conclusions: This is the first analysis evaluating the impact of ATB in mRCC pts treated in the era of ICB. Recent use of ATB prior to ICB, negatively influences responses even after multivariable analysis for prognostic risk factors. Further studies are warranted to investigate whether the alteration of gut microbiota compositions is responsible for this different outcome.

scholarly journals Modified Glasgow Prognostic Score associated with survival in metastatic renal cell carcinoma treated with immune checkpoint inhibitors

2021 ◽  
Vol 9 (7) ◽  
pp. e002851
Author(s):  
Jacqueline T Brown ◽  
Yuan Liu ◽  
Julie M Shabto ◽  
Dylan Martini ◽  
Deepak Ravindranathan ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Immune Checkpoint ◽  
Renal Cell ◽  
Checkpoint Inhibitors ◽  
Prognostic Score ◽  
Univariate Analysis ◽  
Glasgow Prognostic Score ◽  
Modified Glasgow Prognostic Score

BackgroundThe modified Glasgow Prognostic Score (mGPS) is a composite biomarker that uses albumin and C reactive protein (CRP). There are multiple immune checkpoint inhibitor (ICI)-based combinations approved for metastatic renal cell carcinoma (mRCC). We investigated the ability of mGPS to predict outcomes in patients with mRCC receiving ICI.MethodsWe retrospectively reviewed patients with mRCC treated with ICI as monotherapy or in combination at Winship Cancer Institute between 2015 and 2020. Overall survival (OS) and progression-free survival (PFS) were measured from the start date of ICI until death or clinical/radiographical progression, respectively. The baseline mGPS was defined as a summary score based on pre-ICI values with one point given for CRP>10 mg/L and/or albumin<3.5 g/dL, resulting in possible scores of 0, 1 and 2. If only albumin was low with a normal CRP, no points were awarded. Univariate analysis (UVA) and multivariate analysis (MVA) were carried out using Cox proportional hazard model. Outcomes were also assessed by Kaplan-Meier analysis.Results156 patients were included with a median follow-up 24.2 months. The median age was 64 years and 78% had clear cell histology. Baseline mGPS was 0 in 36%, 1 in 40% and 2 in 24% of patients. In UVA, a baseline mGPS of 2 was associated with shorter OS (HR 4.29, 95% CI 2.24 to 8.24, p<0.001) and PFS (HR 1.90, 95% CI 1.20 to 3.01, p=0.006) relative to a score of 0; this disparity in outcome based on baseline mGPS persisted in MVA. The respective median OS of patients with baseline mGPS of 0, 1 and 2 was 44.5 (95% CI 27.3 to not evaluable), 15.3 (95% CI 11.0 to 24.2) and 10 (95% CI 4.6 to 17.5) months (p<0.0001). The median PFS of these three cohorts was 6.7 (95% CI 3.6 to 13.1), 4.2 (95% CI 2.9 to 6.2) and 2.6 (95% CI 2.0 to 5.6), respectively (p=0.0216). The discrimination power of baseline mGPS to predict survival outcomes was comparable to the IMDC risk score based on Uno’s c-statistic (OS: 0.6312 vs 0.6102, PFS: 0.5752 vs 0.5533).ConclusionThe mGPS is prognostic in this cohort of patients with mRCC treated with ICI as monotherapy or in combination. These results warrant external and prospective validation.

191 Association of immune related adverse events with the efficacy of immune checkpoint inhibitors in metastatic renal cell carcinoma

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A205-A206
Author(s):  
Vasilii Bushunow ◽  
Leonard Appleman ◽  
Roby Thomas
Keyword(s):  
Renal Cell Carcinoma ◽  
Adverse Events ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Checkpoint Inhibitors ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Kaplan Meier

BackgroundImmune checkpoint inhibitors (ICI) are first-line therapy for tumors including metastatic renal cell carcinoma (mRCC). Use of ICI is complicated by diverse immune-related adverse events (irAEs), which can add significant morbidity but are also associated with improved efficacy of therapy.1 2 Risk factors for development of irAE are still poorly understood. We hypothesized that patients with mRCC treated with ICI as first-line therapy have higher rates of developing irAE’s than patients previously treated with other therapies.MethodsWe conducted a single-institution, retrospective medical record review of patients with mRCC treated with immune-checkpoint inhibitors from March 2011 through April 15, 2020. We identified therapy duration, and presence, severity, and treatment of adverse events. We defined overall survival as time elapsed from date of diagnosis until death or until completion of study. We classified severity of adverse events according to CTCAE guidelines. Statistical methods included univariate Cox proportional hazards and logistic regression models, and Kaplan-Meier curves were plotted for subgroups.ResultsA total of 64 unique charts were reviewed. 18 patients (28%) of patients were treated with ICI as first-line therapy. 28 patients (44%) experienced immune-related adverse events with a total of 40 irAE’s identified. Most irAE were grade I-II (78%), with 7 (17%) grade III and 1 (2.4%) grade IV irAE’s. Most common sites were skin (29%), thyroid (20%) and gastrointestinal (15%). Patients with irAE had increased survival compared to those who did not have irAE (median survival not reached, vs 139 weeks, p=0.0004) (figure 1). This finding remained after excluding patients who had only experienced dermatologic irAE (median survival not reached in non-derm irAE subgroup, vs 144 weeks for dermatologic or no irAE, p=0.01) (figure 2). Patients treated with ICI as first line therapy had greater rates of developing irAE (72%) than those who had prior therapies (32%) (OR 5.4; p = 0.006). There was no association between histology type and rate of irAE.Abstract 191 Figure 1Kaplan-Meier survival plot of OS between patients with any irAE and those without any irAEAbstract 191 Figure 2Kaplan-Meier survival plot of OS between patients with non-dermatologic irAE and those without any irAE or only dermatologic irAEConclusionsThe development of irAE’s in patients with mRCC treated with ICI is associated with longer survival. This study joins the growing body of evidence showing that presence of irAE’s is associated with increased treatment efficacy. Use of ICI as first-line therapy is associated with higher risk of irAE. Given growing use of ICI as first-line therapy, further study to predict onset and severity of irAE’s is required.AcknowledgementsHong Wang, PhD, for statistical support.Ethics ApprovalThis study was approved by the University of Pittsburgh Institutional Review Board. Approval number STUDY19100386.ReferencesElias R, Yan N, Singla N, Levonyack N, Formella J, Christie A, et al. Immune-related adverse events are associated with improved outcomes in ICI-treated renal cell carcinoma patients. J Clin Oncol 2019;37(7):S645.Verzoni E, Cartenì G, Cortesi E, et al. Real-world efficacy and safety of nivolumab in previously-treated metastatic renal cell carcinoma, and association between immune-related adverse events and survival: the Italian expanded access program. J Immunother Cancer 2019;7(1):99.

scholarly journals Checkpoint inhibitors in patients with metastatic renal cell carcinoma: Results from the International Metastatic Renal Cell Carcinoma Database Consortium

Cancer ◽  
2018 ◽  
Vol 124 (18) ◽  
pp. 3677-3683 ◽  
Author(s):  
Steven M. Yip ◽  
Connor Wells ◽  
Raphael Moreira ◽  
Alex Wong ◽  
Sandy Srinivas ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Checkpoint Inhibitors

MP67-11 THE IMPACT OF MODIFIED INTERNATIONAL METASTATIC RENAL CELL CARCINOMA DATABASE CONSORTIUM MODEL USING A TWO-STEP STRATIFICATION PROCESS

2017 ◽  
Vol 197 (4S) ◽  
Author(s):  
Suguru Shirotake ◽  
Hideyuki Kondo ◽  
Yota Yasumizu ◽  
Koshiro Nishimoto ◽  
Nobuyuki Tanaka ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
The Impact

scholarly journals MP25-05 THE IMPACT OF CYTOREDUCTIVE NEPHRECTOMY IN METASTATIC RENAL CELL CARCINOMA – A REAL-WORLD INVESTIGATION IN THE TKI ERA

2019 ◽  
Vol 201 (Supplement 4) ◽  
Author(s):  
Florian Janisch ◽  
Constantin Fühner ◽  
Christian P. Meyer ◽  
Tobias Hillemacher ◽  
Thomas Klotzbücher ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Real World ◽  
Renal Cell ◽  
Cytoreductive Nephrectomy ◽  
The Impact

The Impact of PBRM1 Expression as a Prognostic and Predictive Marker in Metastatic Renal Cell Carcinoma

2015 ◽  
Vol 194 (4) ◽  
pp. 1112-1119 ◽  
Author(s):  
Ji-Yeon Kim ◽  
Se-Hoon Lee ◽  
Kyung Chul Moon ◽  
Cheol Kwak ◽  
Hyeon Hoe Kim ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Predictive Marker ◽  
The Impact
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