Novel risk scoring system for metastatic renal cell carcinoma (mRCC) patients (pts) treated with cabozantinib (C).

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 734-734
Author(s):  
Meredith R Kline ◽  
Dylan J. Martini ◽  
Yuan Liu ◽  
Julie M. Shabto ◽  
Bradley Curtis Carthon ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Scoring System ◽  
Group Performance ◽  
Eastern Cooperative Oncology Group ◽  
Risk Scoring ◽  
Ecog Ps ◽  
Risk Scoring System

734 Background: Cabozantinib (C) is an effective treatment for metastatic renal cell carcinoma (mRCC) patients (pts). The international mRCC database consortium (IMDC) criteria is the gold standard for mRCC risk stratification. We created a risk scoring system for mRCC pts treated with C. Methods: We performed a retrospective review of 87 mRCC pts treated with C at Winship Cancer Institute from 2015-19. Overall survival (OS) and progression free survival (PFS) were defined as months from C initiation. The baseline characteristics and inflammation biomarkers included were monocyte, neutrophil, and platelet-to-lymphocyte ratios (MLR, NLR, and PLR respectively), RCC histology, body mass index (BMI), metastatic sites (mets), and Eastern Cooperative Oncology Group performance status (ECOG PS). Upon variable selection in multivariable analysis (MVA), elevated baseline MLR (≥0.71), presence of sarcomatoid histology, ECOG PS > 1, and absence of bone metastases were assigned 1 point. A three-level risk scoring system was created: low (score = 0-1), intermediate (score = 2), and high risk (score = 3-4). The Kaplan-Meier method, Cox proportional hazard model, and Uno’s C-statistics were used to examine performance. Results: The majority of pts were males (71%) with clear-cell RCC (75%). Most pts (67%) received 1+ prior line of therapy. High and intermediate risk pts had significantly shorter OS and PFS compared to low risk pts (Table). The C-statistics for our risk scoring system were higher than IMDC in predicting OS (0.7 vs. 0.62) and PFS (0.65 vs 0.57). Conclusions: Pts treated with C may benefit from risk scoring using RCC histology, ECOG PS, mets, and MLR. These results are hypothesis-generating and should be validated in a larger study.[Table: see text]

scholarly journals Novel risk scoring system for metastatic renal cell carcinoma patients treated with cabozantinib

2021 ◽  
pp. 100393
Author(s):  
Dylan J. Martini ◽  
Meredith R. Kline ◽  
Yuan Liu ◽  
Julie M. Shabto ◽  
Bradley C. Carthon ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Scoring System ◽  
Risk Scoring ◽  
Risk Scoring System

Rechallenge of nivolumab in metastatic renal cell carcinoma, an ambispective multicenter study (RENIVO).

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 330-330
Author(s):  
Charles Vauchier ◽  
Edouard Auclin ◽  
Philippe Barthelemy ◽  
Lucia Carril ◽  
Thomas Ryckewaert ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Multicenter Study ◽  
Renal Cell ◽  
Group Performance ◽  
Checkpoint Inhibitors ◽  
Single Agent ◽  
Eastern Cooperative Oncology Group ◽  
Grade 3

330 Background: Immune checkpoint inhibitors (ICIs) in combination with another ICI or an antiangiogenic targeted therapy have been approved for frontline therapy in metastatic renal cell carcinoma (mRCC). However, progression disease (PD) often occurs and subsequent therapies are needed. Rechallenge of ICI may then be an option, but there is a lack of data regarding this strategy. Methods: This ambispective multicenter study included patients who received a rechallenge of Nivolumab (ICI-2) between January 2014 and September 2020, after a first-ICI therapy (ICI-1), regardless of the reason of the discontinuation. Patients could have either a non-ICI therapy or have a prolonged free-interval (≥ 12 weeks) between ICI regimens. Those with ongoing rechallenge at inclusion were followed prospectively. Primary endpoint was investigator-assessed best ORR. Results: 45 rechallenges were included from 16 centers. Median age was 60 years (range, 42-90), 64% were male. Most of them had clear cell histology (91%) and a Fuhrman or ISUP grade ≥ 3 (80%). Single-agent Nivolumab and Nivolumab-Ipilimumab association were used in 78% and 11% during ICI-1 and in 93% and 7% during ICI-2, respectively. Discontinuation for PD, toxicity or clinical decision occurred in 49%, 27% and 24% for ICI-1 and in 94%, 3% and 3% for ICI-2, respectively. The ORR were 51% (n = 23) at ICI-1 and 16% (n = 7) at ICI-2. One patient had a complete response during both ICI-1 and ICI-2 and two had a partial response at ICI-2 although they had PD as best ICI-1 response. After a median follow-up of 14.9 months (mo), median duration of response for ICI-2 was 5.1 mo (95% CI, 2.7-not reached [NR]). For ICI-1 and ICI-2: median progression-free survival (PFS) was 11.4 mo (95% CI, 9.8-23.5) and 3.5 mo (95% CI, 2.8-9.7); median overall survival was NR (95% CI, 37.8-NR) and 24 mo (95% CI, 9.9-NR). Poor prognostic factors for PFS at ICI-2 were Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≥ 2, presence of liver metastases, inflammatory syndrome and PFS under ICI-1 > 6 months. Grade ≥ 3 immune-related adverse events occurred in 24% (n = 11) during ICI-1 but only in 4% (n = 2) during ICI-2. There was no treatment-related death. Conclusions: Our study suggests that resumption of ICI with Nivolumab has a moderate efficacy in mRCC and acceptable tolerance. Predictive factors of response are needed to propose this strategy to selected mRCC patients. Larger prospective cohorts are needed to confirm these results. [Table: see text]

Results of treatment of 255 patients with metastatic renal cell carcinoma who received high-dose recombinant interleukin-2 therapy.

1995 ◽  
Vol 13 (3) ◽  
pp. 688-696 ◽  
Author(s):  
G Fyfe ◽  
R I Fisher ◽  
S A Rosenberg ◽  
M Sznol ◽  
D R Parkinson ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Objective Response ◽  
Eastern Cooperative Oncology Group ◽  
Interleukin 2 ◽  
High Dose ◽  
Primary Tumors ◽  
Median Response

PURPOSE To determine the efficacy and toxicity of a high-dose interleukin-2 (IL-2) regimen in patients with metastatic renal cell carcinoma. PATIENTS AND METHODS Two hundred fifty-five assessable patients were entered onto seven phase II clinical trials. Proleukin (aldesleukin; Chiron Corp, Emeryville, CA) 600,000 or 720,000 IU/kg was administered by 15-minute intravenous (i.v.) infusion every 8 hours for up to 14 consecutive doses over 5 days as clinically tolerated with maximum support, including pressors. A second identical cycle of treatment was scheduled following 5 to 9 days of rest, and courses could be repeated every 6 to 12 weeks in stable or responding patients. RESULTS The overall objective response rate was 14% (90% confidence interval [CI], 10% to 19%), with 12 (5%) complete responses (CRs) and 24 (9%) partial responses (PRs). Responses occurred in all sites of disease, including bone, intact primary tumors, and visceral metastases, and in patients with large tumor burdens or bulky individual lesions. The median response duration for patients who achieved a CR has not been reached, but was 19.0 months for those who achieved a PR. Baseline Eastern Cooperative Oncology Group (ECOG) performance status (PS) was the only predictive prognostic factor for response to IL-2. While treatment was associated with severe acute toxicities, these generally reversed rapidly after therapy was completed. However, 4% of patients died of adverse events judged to be possibly or probably treatment-related. CONCLUSION High-dose IL-2 appears to benefit some patients with metastatic renal cell carcinoma by producing durable CRs or PRs. Despite severe acute treatment-associated toxicities, IL-2 should be considered for initial therapy of patients with appropriately selected metastatic renal cell carcinoma.

Use of STAT3 polymorphisms to predict overall survival in patients treated with interferon-alpha for metastatic renal cell carcinoma.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e15048-e15048
Author(s):  
Masatoshi Eto ◽  
Tomomi Kamba ◽  
Hideaki Miyake ◽  
Masato Fujisawa ◽  
Takao Kamai ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Overall Survival ◽  
Prospective Study ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Progression Free Survival ◽  
Nucleotide Polymorphisms ◽  
Logrank Test ◽  
Ecog Ps

e15048 Background: We previously reported that the single nucleotide polymorphisms (SNPs) in signal transducer and activator 3 (STAT3) gene were most significantly associated with better response to interferon (IFN)-α in patients with metastatic renal cell carcinoma (mRCC) in our retrospective analysis (JCO 25:2785, 2007). We conducted this trial to prospectively confirm the results, and reported the significant association between the SNPs of STAT3-2 and clinical benefits (CR, PR, and SD more than 24 weeks) of IFN-α (p = 0.039) (ASCO 2011, abstract No. 4590). In this study, we have further analyzed the correlation between overall survival (OS), progression-free survival (PFS) and the 11 SNPs reported previously. Methods: In this multicenter, prospective study, patients with histologically confirmed RCC that was metastatic, measurable disease, age > 20 years, ECOG PS 0-1 and adequate organ function received 3 dosages of 5 million U per week of IFN-α treatment. We evaluated the correlation between OS, PFS and SNP allele frequencies of STAT3-2, STAT3-0, SOCS3-1, IL4R-34, PTGS1-3, PTGS1-4, PTGS1-5, PTGS2-12, IRF2-67, ICSBP-38, and TAP2-5 (JCO 25:2785, 2007) in mRCC patients treated with IFN-α. Association between OS, PFS and genetic polymorphisms was analyzed using Logrank test for trend. Results: Two hundreds three eligible patients were enrolled between December 2006 and October 2009. All patients had prior nephrectomy, and 88.7% had ECOG PS 0. Ninety-four percent of patients had clear cell RCC, and 5% had papillary RCC. At the time of this analysis the central review assessed response rate was 13.8% (28/203) (9 CR, 19 PR). CR rate of 4.4% (9/203) was more than we expected. PFS was not associated with any of the 11 SNPs examined. However, 2 SNPs of STAT3 gene, STAT3-2 and STAT3-0, were significantly associated with OS, and the correlation of STAT3-2 (p = 0.0347) was stronger than that of STAT3-0. Namely, C/C genotype of STAT3-2 was significantly associated with prolonged OS compared with the other genotypes (C/T and T/T). Conclusions: This is the first prospective study demonstrating that STAT3 polymorphisms can predict OS in mRCC patients treated with IFN-α.

Prognostic factors for metastatic renal cell carcinoma patients with removed metastases: A multicenter study of 559 patients.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e15071-e15071
Author(s):  
Sei Naito ◽  
Hidefumi Kinoshita ◽  
Tsunenori Kondo ◽  
Nobuo Shinohara ◽  
Takashi Kasahara ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Overall Survival ◽  
Prognostic Factors ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Median Overall Survival ◽  
Group Performance ◽  
Hazard Ratio ◽  
Incomplete Resection

e15071 Background: Metastasectomy considered to prolong survival in patients with metastatic renal cell carcinoma (mRCC). However, data on the indications for metastasectomy are limited. We aimed to examine the prognosis and the prognostic factors of mRCC patients who underwent metastasectomy. Methods: We sent questionnaires to Japanese hospitals and collected the data of patients who were diagnosed with mRCC between January 1988 and December 2009 and who had their metastatic lesions removed. We calculated the overall survival between metastasectomy and death or until the last follow-up. We also analyzed the relationship between survival and clinical features and identified adverse prognostic factors by multivariate analysis. Furthermore, we identified the group with a poor prognosis on the basis of the number of prognostic factors for which the patients were positive. These findings were internally validated using bootstrap procedures and the c-index. Results: We collected the data of 559 patients from 48 institutions. The median overall survival period was 80 months (95% CI, 69.7-90.6 months). We detected 5 adverse prognostic factors: incomplete resection by metastasectomy (hazard ratio, 1.75; p = 0.0169); brain metastasis (hazard ratio, 3.26; p = 0.0002); C-reactive protein levels of >1.0 mg/dl (hazard ratio, 2.84; p < 0.0001); Eastern Cooperative Oncology Group performance status of >1 (hazard ratio, 1.65; p = 0.0274); and the worst nuclear grade, i.e., the nuclei of tumor cells are larger than those of normal tubular cells (hazard ratio, 1.59; p = 0.0348). Patients positive for 3 or more of theseadverse prognostic factors had a worse prognosis (median overall survival, 24 months) than those positive for less than 3 factors (median overall survival, 105 months). The c-index for this model was 0.65 at 2 years. Conclusions: We identified 5 adverse prognostic factors for predicting the survival of patients who underwent metastasectomy.

Comorbidity and other predictors of survival in veterans with metastatic renal cell carcinoma (RCC).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e15561-e15561
Author(s):  
Michael Cho ◽  
Trent P Wang ◽  
Melanie L. Gonzalez ◽  
Victor T Chang ◽  
Fengming Zhong ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Co Morbidity ◽  
Signal Transduction Inhibitors ◽  
History Of ◽  
Ecog Ps

e15561 Background: Comorbidity as a prognostic marker has been reported in several solid tumors. We examined whether co-morbidity indices predict survival in Veterans with metastatic renal cell carcinoma (RCC) who were treated with signal transduction inhibitors. Methods: In an IRB-approved protocol, we reviewed the records of patients (Pts) diagnosed with RCC at a VA Medical Center from 1/1/2000 to 12/31/2011. Age, ECOG Performance Status (ECOG PS), Hemoglobin (Hgb), Albumin (Alb), Corrected Calcium (CCa), history of Nephrectomy, and histology (clear cell (CC) vs. non clear cell (NCC)) were abstracted. Co-morbidity was assessed with Charlson Comorbidity Index (CCI), and the Kaplan-Feinstein Index (KFI). We developed a survival model with age, ECOG PS, Hgb, Alb, CCa, history of nephrectomy, and histology. Co-morbidity indices were tested by determining if they were independent predictors of survival after inclusion in this model. Cox regression analyses were performed with SAS V9.2. Results: There were 24 Pts;6 (25%) are alive. The Median (M) age when seen at VA was 64 years (54-85). The M Hgb level was 12.1g/dL (6.7-16.5), Alb was 4.1g/dL (2.8-5.0), and CCa was 9.19mg/dL (7.9-12.5). The M CCI was 4.2 (1.4-12.0) and KFI was 2.0 (1-3). The M Survival was 823 days (24-3482). 17(68%) pts had clear cell carcinoma and 18(72%) had nephrectomies Median ECOG PS was one range(0-4). The median number of treatments was 2, range 1-7. Results of univariate analyses with co-morbidity indices were significant for age (p < ,029) and history of nephrectomy p< .068). There were no multivariate predictors of survival. Conclusions: In the univariate analysis, ECOG PS as well as Nephrectomy status were significant predictors for M survival. CCI and KFI did not predict M survival. In distinction to other solid tumor histologies where chemotherapy is used, KFI and CCI in RCC may not be associated with overall survival due to either RCC histology or use of signal transduction inhibitors as treatment. Confirmatory studies should be done in larger populations. This was supported by the New Jersey Commission for Cancer Research.

scholarly journals Clinical and Pathological Characteristics of Metastatic Renal Cell Carcinoma Patients Needing a Second-Line Therapy: A Systematic Review

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3634
Author(s):  
Nicola Longo ◽  
Marco Capece ◽  
Giuseppe Celentano ◽  
Roberto La Rocca ◽  
Gianluigi Califano ◽  
...  
Keyword(s):  
Systematic Review ◽  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Group Performance ◽  
Second Line ◽  
First Line ◽  
Second Line Therapy ◽  
Line Therapy

A high percentage of patients with metastatic renal cell carcinoma (mRCC) require a second-line option. We aimed to summarize available evidences about the clinicopathological profile of mRCC patients who receive a second-line therapy. A systematic review was performed in August 2020. We included papers that met the following criteria: original research; English language; human studies; enrolling mRCC patients entering a second-line therapy. Twenty-nine studies enrolling 7650 patients (73.5% male, mean age: 55 to 70 years) were included. Clear cell histology was reported in 74.4% to 100% of cases. Tyrosine kinase inhibitors, immunotherapy, bevacizumab, mTOR inhibitors, and chemotherapy were adopted as first line option in 68.5%, 29.2%, 2.9%, 0.6%, and 0.2% of patients, respectively. Discontinuation of first-line therapy was due to progression and toxicity in 18.4% to 100% and in 17% to 48.8% of patients, respectively. Eastern Cooperative Oncology Group performance status score was 0 or 1 in most cases. Most prevalent prognostic categories according to the International Metastatic RCC Database Consortium and Memorial Sloan–Kettering Cancer Centre score were intermediate and good. About 77.8% of patients harboured ≥2 metastatic sites. In conclusion, patients who enter a second-line therapy are heterogeneous in terms of a clinical-pathological profile. Tailoring of second-line treatment strategies is strongly advocated.

scholarly journals Real-world use of temsirolimus in Japanese patients with unresectable or metastatic renal cell carcinoma: recent consideration based on the results of a post-marketing, all-case surveillance study

2020 ◽  
Vol 50 (8) ◽  
pp. 940-947
Author(s):  
Shigeru Sugiyama ◽  
Kazuo Sato ◽  
Yoshiyuki Shibasaki ◽  
Yutaka Endo ◽  
Taku Uryu ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Interstitial Lung Disease ◽  
Confidence Interval ◽  
Lung Disease ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Group Performance ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Data Set

Abstract Objective A prospective, observational, post-marketing surveillance was conducted to assess the safety and effectiveness of temsirolimus in patients with renal cell carcinoma in Japan. Methods Patients prescribed temsirolimus for advanced renal cell carcinoma were registered and received temsirolimus (25 mg weekly, intravenous infusion for 30–60 minutes) in routine clinical settings (observation period: 96 weeks). Results Among 1001 patients included in the safety analysis data set (median age, 65.0 years; men, 74.8%; Eastern Cooperative Oncology Group performance status 0 or 1, 69.6%), 778 (77.7%) reported adverse drug reactions. The most common (≥10%) all-grade adverse drug reactions were stomatitis (26.7%), interstitial lung disease (17.3%) and platelet count decreased (11.1%). The incidence rate of grade ≥3 interstitial lung disease was 4.5%. The onset of interstitial lung disease was more frequent after 4–8 weeks of treatment or in patients with lower Eastern Cooperative Oncology Group performance status (21.6% for score 0 vs 8.3% for score 4, P &lt; 0.001). Among 654 patients in the effectiveness analysis data set, the response and clinical benefit rates were 6.7% (95% confidence interval 4.9–8.9) and 53.2% (95% confidence interval 49.3–57.1), respectively. The median progression-free survival was 18.3 weeks (95% confidence interval 16.9–21.1). Conclusions The safety and effectiveness profile of temsirolimus observed in this study was similar to that observed in the multinational phase 3 study. The results are generalizable to the real-world scenario at the time of this research, and safety and effectiveness of temsirolimus as a subsequent anticancer therapy for renal cell carcinoma warrants further investigation. (ClinicalTrials.gov identifier NCT01210482, NCT01420601).

Sign in / Sign up

Export Citation Format

Share Document