Immunotherapy of advanced renal cell carcinoma

1996 ◽  
Vol 63 (4) ◽  
pp. 451-457
Author(s):  
F. De Braud ◽  
T. De Pas ◽  
M. Maffezzini
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Overall Response Rate ◽  
Response Rate ◽  
Cost Benefit ◽  
Cytotoxic Chemotherapy ◽  
Advanced Renal Cell Carcinoma ◽  
Therapeutic Approaches ◽  
The Cost

Although many different treatments have been evaluated in the last thirty years, advanced renal cell carcinoma still has a poor prognosis, characterised by a survival rate which is less than 5% at 3 years from diagnosis. Many different therapeutic approaches have been carried out in addition to cytotoxic chemotherapy, which shows obvious limits such as an overall response rate that does not go above 10-15%. One of the more promising treatments that has been studied the most is undoubtedly immunotherapy. We present a literature review aimed at summing up all the results obtained until now with immunotherapy of renal cell carcinoma, whether alone or in combination with cytotoxic chemotherapy. Unanswered questions of major concern are stressed, such as treatment choice, dosage, the most convenient schedules with particular regard to the cost-benefit issue.

Response to systemic therapy in non-clear cell renal cell carcinomas: A systematic review and meta-analysis.

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 425-425 ◽  
Author(s):  
Francisco Emilio Vera-Badillo ◽  
Arnoud Templeton ◽  
Alberto Ocana ◽  
Paulo deGouveia ◽  
Priya Aneja ◽  
...  
Keyword(s):  
Systematic Review ◽  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Systemic Therapy ◽  
Renal Cell ◽  
Overall Response Rate ◽  
Response Rate ◽  
Clear Cell ◽  
Meta Analysis ◽  
Cell Renal Cell Carcinoma

425 Background: Clinical data supporting the efficacy of systemic therapy in non-clear cell renal cell carcinoma (non-ccRCC) are limited and based on retrospective analyses, expanded access programs and single arm phase II trials. Therefore the optimal treatment for this subgroup remains uncertain. Methods: A systematic review of electronic databases was conducted to identify publications evaluating the outcomes of patients with non-ccRCC (excluding those with sarcomatoid tumors) treated with different systemic approaches (immunotherapy, chemotherapy, targeted agents, small molecules). The primary endpoint was response rate and secondary endpoints were median progression free (PFS) and overall survival (OS). Where possible, data were pooled in a meta-analysis using the Mantel-Haenszel random-effect modeling. For studies comprising of unselected patients, outcomes of those with non-ccRCC were compared with clear cell renal cell carcinoma (ccRCC). Results: Forty-nine studies comprising 7,799 patients were included: 471 patients were enrolled on studies conducted exclusively in non-ccRCC and 7,328 patients on studies of unselected renal cell carcinoma. Among these, 903 (12%) had non-ccRCC and 6,425 (88%) had ccRCC. For non-ccRCC, overall response rate, median PFS and median OS were 9%, 7.9 and 13.4 months, respectively. By comparison, the overall response rate for ccRCC was 15% (Risk Ratio for response [RR] 0.67, 95% CI 0.52-0.86, p=0.002). This association was independent of type of treatment administered. Among the different novel agents (bevacizumab, lenalidomide, linefanib, sorafenib, sunitinib, pazopanib, everolimus and temsirolimus), sunitinib was significantly less efficacious in non-ccRCC than ccRCC (RR 0.56, 95% CI 0.42-0.72), but there was no significant difference in response rates for sorafenib (RR 0.64, 95% CI 0.31-1.35) or other agents (RR 1.10, 95% CI 0.50-2.44), However, confidence intervals were wide. Results of further analyses will be presented at the meeting. Conclusions: Patients with non-ccRCC have lower response rates than those with ccRCC, but the absolute difference between them is modest. Further study of targeted therapy in non-ccRCC is warranted.

scholarly journals Cost-Effectiveness of Frontline Treatment for Advanced Renal Cell Carcinoma in the Era of Immunotherapies

2021 ◽  
Vol 12 ◽  
Author(s):  
SiNi Li ◽  
JianHe Li ◽  
LiuBao Peng ◽  
YaMin Li ◽  
XiaoMin Wan
Keyword(s):  
Renal Cell Carcinoma ◽  
Cost Effectiveness ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Transition Probability ◽  
Cost Effective ◽  
Sensitivity Analyses ◽  
Advanced Renal Cell Carcinoma ◽  
Life Years ◽  
The Cost

Background: Recent randomized controlled trials have demonstrated that immune checkpoint inhibitors (ICIs) improve patient outcomes, but whether these novel agents are cost-effective for untreated advanced renal cell carcinoma (aRCC) remains unclear.Materials and Methods: A microsimulation model was created to project the healthcare costs and outcomes of six strategies (lenvatinib-plus-pembrolizumab, nivolumab-plus-cabozantinib, nivolumab-plus-ipilimumab, pembrolizumab-plus-axitinib, avelumab-plus-axitinib, and sunitinib monotherapy) for patients with aRCC. Transition probability of patients was estimated from CLEAR, CheckMate 9ER, CheckMate 214, KEYNOTE-426, JAVELIN Renal 101, and other data sets by using parametric survival modeling. Lifetime direct medical costs, life years (LYs), quality-adjusted LYs (QALYs), and incremental cost-effectiveness ratios (ICERs) were estimated from a United States payer perspective. One-way and probabilistic sensitivity analyses were performed, along with multiple scenario analyses, to evaluate model uncertainty.Results: Of the six competing strategies, nivolumab-plus-cabozantinib yielded the most significant health outcomes, and the sunitinib strategy was the least expensive option. The cost-effective frontier consisted of the nivolumab-plus-cabozantinib, pembrolizumab-plus-axitinib, and sunitinib strategies, which displayed the ordered ICERs of $81282/QALY for pembrolizumab-plus-axitinib vs sunitinib and $453391/QALY for nivolumab-plus-cabozantinib vs pembrolizumab-plus-axitinib. The rest of the strategies, such as lenvatinib-plus-pembrolizumab, nivolumab-plus-ipilimumab, and avelumab-plus-axitinib, were dominated. The cost of sunitinib drove the model most influentially.Conclusions: For aRCC, the pembrolizumab-plus-axitinib strategy is likely to be the most cost-effective alternative at the willingness-to-pay threshold of $100,000.

Combination therapy of meloxicam, a selective COX-2 inhibitor, and interferon alfa in metastatic renal cell carcinoma: A phase II study on efficacy and toxicity

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 5105-5105 ◽  
Author(s):  
N. Shinohara ◽  
T. Harabayashi ◽  
A. Sazawa ◽  
K. Nonomura ◽  
Y. Watarai ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Phase Ii ◽  
Renal Cell ◽  
Overall Response Rate ◽  
Response Rate ◽  
Antitumor Effects ◽  
Overall Response ◽  
Cox 2 ◽  
Metastatic Rcc

5105 Background: Cyclooxygenase (COX)-2 plays a major role in the development of cancer through numerous mechanisms. We have previously confirmed that COX-2 is expressed in a renal cell carcinoma (RCC) and it has an important role in tumorigenesis and angiogenesis (Int J Cancer 2004). Some preclinical studies suggest that a selective COX-2 inhibitor may augment the antitumor effects of immunotherapeutic agents. We conducted a phase II trial of the combination of meloxicam, a selective COX-2 inhibitor, and interferon (IFN)-alfa 2a in metastatic RCC in order to test the hypothesis that meloxicam enhances the response to the immunotherapy. Methods: Eligible patients had metastatic RCC, no prior systemic therapy, performance status 0–2, measurable disease. Patients received IFN 3–5 MIU 3x/week and meloxicam 10 mg/daily orally. This was a single-stage trial. Primary end points were RECIST response rates and toxicity. Results: Twenty-one patients were enrolled. Patients characteristics included: median age 63 years (49–75), male/female: 16/5, PS 0/1/2: 11/6/4, prior nephrectomy: 16 (76%). MSKCC prognostic categories were good: intermediate: poor (24%: 48%: 29%). A median follow-up was 8 months (range 3–29+) and 18 of 21 (86%) patients are still alive. Toxicities were mostly grade 1 or 2 (fever, fatigue, anorexia, depression), except 1 patient with grade 3 liver dysfunction. Among 20 patients evaluable for response, complete response (CR) was observed in 3 patients (15%) and partial response (PR) in 5 (25%), yielding an overall response rate of 40% (95% CI: 17–63). An additional 5 patients (25%) had stable disease. Five of 6 patients classified as poor risk by MSKCC prognostic classification obtained a CR or PR, as did 3 of 14 patients as good or intermediate risk (p=0.038). Median time to progression for 20 patients was 6 months (1–29+). Conclusions: The overall response rate of 40% for the combination of meloxicam and IFN-alfa in metastatic RCC is greater than that of IFN-alfa alone reported previously, suggesting that meloxicam can enhance the response to immunotherapy. Further investigation with this combination is warranted. No significant financial relationships to disclose.

Combination of antiangiogenic therapy and cytotoxic chemotherapy for sarcomatoid renal cell carcinoma.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 4512-4512
Author(s):  
M Dror Michaelson ◽  
David F. McDermott ◽  
Michael B. Atkins ◽  
Daniel C. Cho ◽  
Kara M. Olivier ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Response Rate ◽  
Treatment Options ◽  
Antiangiogenic Therapy ◽  
Prospective Trial ◽  
Cytotoxic Chemotherapy ◽  
Sarcomatoid Differentiation

4512 Background: Numerous treatment options exist for metastatic renal cell carcinoma (mRCC), but optimal treatment for patients (pts) with sarcomatoid features remains undefined. Sarcomatoid differentiation is a particularly unfavorable prognostic feature in mRCC. Cytotoxic chemotherapy has modest activity, with a response rate of 16% for doxorubicin plus gemcitabine (Gem). Retrospective data has suggested a response rate of 10% for antiangiogenic therapy. We prospectively studied the combination of antiangiogenic therapy, sunitinib (Su), with Gem chemotherapy in this mRCC subpopulation. Methods: Pts with mRCC and sarcomatoid differentiation were enrolled in a phase 2 clinical trial at 3 institutions. Treatment consisted of 21-day cycles of Su, 37.5 mg on a 2 weeks on/1 week off schedule, along with Gem 1000 mg/m2 on days 1 and 8. The primary endpoint was radiographic response rate (RR) by RECIST. Secondary endpoints included time to disease progression (TTP), safety, and overall survival (OS). Results: Among 35 pts treated in total, 7 were classified as MSKCC good risk, 26 as intermediate risk, and 2 as poor risk. There were 10 partial responses and 1 complete response, for a confirmed RR of 30%. An additional 10 pts exhibited stable disease (clinical benefit rate 60%). Among the 10 pts who had progressive disease as their best response, the majority had underlying non-clear cell histology. Median TTP was 3.5 months (range 0.5-12). Eight pts discontinued due to adverse events (AEs). The most common treatment-emergent grade 3 or higher AEs were neutropenia (8 pts), fatigue (5), anemia (2), and hypertension (2). No treatment-related deaths occurred. Median OS was 11 months (range 1-38+). Conclusions: To our knowledge, this is the largest prospective trial combining cytotoxic chemotherapy and antiangiogenic therapy in patients with RCC and sarcomatoid features. Our results suggest that combination therapy may be more efficacious than either treatment alone in this subtype of mRCC and supports an ongoing intergroup trial (NCT01164228). Further research is necessary to define prognostic factors, including histologic and molecular biomarkers, for distinct subpopulations within this heterogeneous disease. Clinical trial information: NCT00556049.

Cytotoxic chemotherapy in the treatment of advanced renal cell carcinoma in the era of targeted therapy

2015 ◽  
Vol 96 (3) ◽  
pp. 518-526 ◽  
Author(s):  
E. Diamond ◽  
A.M. Molina ◽  
M. Carbonaro ◽  
N.H. Akhtar ◽  
P. Giannakakou ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Targeted Therapy ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Cytotoxic Chemotherapy ◽  
Advanced Renal Cell Carcinoma

CheckMate 214 post-hoc analyses of nivolumab plus ipilimumab or sunitinib in IMDC intermediate/poor-risk patients with previously untreated advanced renal cell carcinoma with sarcomatoid features.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 4513-4513 ◽  
Author(s):  
David F. McDermott ◽  
Toni K. Choueiri ◽  
Robert J. Motzer ◽  
Osvaldo Rudy Aren ◽  
Saby George ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Keyword Search ◽  
Response Rate ◽  
Clear Cell ◽  
Objective Response ◽  
Advanced Renal Cell Carcinoma ◽  
Pathology Reports ◽  
Post Hoc

4513 Background: Patients (pts) with advanced renal cell carcinoma with sarcomatoid features (sRCC) have poor prognosis and suboptimal outcomes with anti-VEGF targeted therapy. Nivolumab plus ipilimumab (N+I) demonstrated superior objective response rate (ORR) and overall survival (OS) vs sunitinib (S) in previously untreated pts with International Metastatic RCC Database Consortium (IMDC) intermediate/poor (I/P)-risk, clear-cell, advanced RCC in the phase 3 CheckMate 214 trial. Methods: We performed a post-hoc exploratory analysis of N+I vs S in CheckMate 214 sRCC pts. The presence of sarcomatoid features was assessed by keyword search for “sarcomatoid” in pts with available local pathology reports accompanying pretreatment tumor samples. Results: 842 (77%) of 1096 intention-to-treat pts had local pathology reports available, including 112 randomized pts with I/P-risk sRCC (N+I, n = 60; S, n = 52). Baseline characteristics of sRCC pts were balanced between arms. Notably, 47% vs 53% of I/P-risk sRCC pts in the N+I and S arms had tumor PD-L1 expression ≥1% at baseline, which was higher than in all I/P-risk pts (N+I, 26% vs S, 29%). In descriptive analyses performed at a minimum follow-up of 30 months, confirmed ORR and complete response rate per investigator (RECIST v1.1), OS, and progression-free survival (PFS) per investigator were improved with N+I vs S in I/P-risk pts with sRCC (Table). No new safety signals were seen in sRCC pts. Conclusions: In this post-hoc descriptive subgroup analysis of CheckMate 214, N+I demonstrated promising efficacy and prolonged survival vs S, with consistent safety, in previously untreated, I/P-risk, advanced clear-cell RCC with sarcomatoid features. Prospective studies of N+I that include pts with sRCC are ongoing. Clinical trial information: NCT02231749. [Table: see text]

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