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]

Modest efficacy of nivolumab plus ipilimumab in patients with papillary renal cell carcinoma

2020 ◽  
Author(s):  
Hidekazu Tachibana ◽  
Tsunenori Kondo ◽  
Hiroki Ishihara ◽  
Hironori Fukuda ◽  
Kazuhiko Yoshida ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Response Rate ◽  
Clear Cell ◽  
Objective Response ◽  
Progression Free Survival ◽  
Papillary Renal Cell Carcinoma ◽  
Cell Renal Cell Carcinoma ◽  
Free Survival

Abstract Purpose Combined immunotherapy of nivolumab plus ipilimumab for intermediate- and poor-risk metastatic clear cell renal cell carcinoma showed prolonged progression-free survival and high objective response rate in a randomized phase III clinical trial. However, the efficacy of this treatment for papillary renal cell carcinoma remains unclear. In the present study, we analysed the efficacy of nivolumab plus ipilimumab therapy for papillary renal cell carcinoma compared with that for clear cell renal cell carcinoma. Materials and Methods This is a retrospective study of 30 patients with metastatic renal cell carcinoma who received nivolumab and ipilimumab as first-line therapy between December 2015 and May 2020. The objective response rate, progression-free survival and toxicity were compared between the two groups (clear cell renal cell carcinoma and papillary renal cell carcinoma). Results Out of 30 patients, 7 and 23 were diagnosed with papillary renal cell carcinoma and clear cell renal cell carcinoma, respectively. With a median follow-up of 7.2 months, the median progression-free survival was significantly shorter in papillary renal cell carcinoma than in clear cell renal cell carcinoma (2.4 vs. 28.1 months, P = 0.014). Of the seven patients with papillary renal cell carcinoma, one had partial response, one had stable disease and five had progressive disease, resulting in an objective response rate of 14.2%, which was lower compared to that of clear cell renal cell carcinoma (14.2 vs. 52.1%, P = 0.06). Discontinuation due to toxicity was not observed with papillary renal cell carcinoma, meanwhile 60.8% of patient with clear cell renal cell carcinoma discontinued treatment due to toxicity. Conclusion Nivolumab plus ipilimumab had modest efficacy for papillary renal cell carcinoma compared with that for clear cell renal cell carcinoma. Nivolumab plus ipilimumab remains an option for a limited number of patients with intermediate- or poor-risk papillary renal cell carcinoma.

scholarly journals Quality of Life Outcomes for Cabozantinib Versus Everolimus in Patients With Metastatic Renal Cell Carcinoma: METEOR Phase III Randomized Trial

2018 ◽  
Vol 36 (8) ◽  
pp. 757-764 ◽  
Author(s):  
David Cella ◽  
Bernard Escudier ◽  
Nizar M. Tannir ◽  
Thomas Powles ◽  
Frede Donskov ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Renal Cell Carcinoma ◽  
Bone Metastases ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Repeated Measures ◽  
Objective Response ◽  
Phase Iii ◽  
Advanced Renal Cell Carcinoma

Purpose In the phase III METEOR trial ( ClinicalTrials.gov identifier: NCT01865747), 658 previously treated patients with advanced renal cell carcinoma were randomly assigned 1:1 to receive cabozantinib or everolimus. The cabozantinib arm had improved progression-free survival, overall survival, and objective response rate compared with everolimus. Changes in quality of life (QoL), an exploratory end point, are reported here. Patients and Methods Patients completed the 19-item Functional Assessment of Cancer Therapy–Kidney Symptom Index (FKSI-19) and the five-level EuroQol (EQ-5D-5L) questionnaires at baseline and throughout the study. The nine-item FKSI–Disease-Related Symptoms (FKSI-DRS), a subset of FKSI-19, was also investigated. Data were summarized descriptively and by repeated-measures analysis (for which a clinically relevant difference was an effect size ≥ 0.3). Time to deterioration (TTD) was defined as the earlier of date of death, radiographic progressive disease, or ≥ 4-point decrease from baseline in FKSI-DRS. Results The QoL questionnaire completion rates remained ≥ 75% through week 48 in each arm. There was no difference over time for FKSI-19 Total, FKSI-DRS, or EQ-5D data between the cabozantinib and everolimus arms. Among the individual FKSI-19 items, cabozantinib was associated with worse diarrhea and nausea; everolimus was associated with worse shortness of breath. These differences are consistent with the adverse event profile of each drug. Cabozantinib improved TTD overall, with a marked improvement in patients with bone metastases at baseline. Conclusion In patients with advanced renal cell carcinoma, relative to everolimus, cabozantinib generally maintained QoL to a similar extent. Compared with everolimus, cabozantinib extended TTD overall and markedly improved TTD in patients with bone metastases.

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.

Correlation of insulin-receptor expression with efficacy of axitinib in patients with advanced renal cell carcinoma.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 442-442
Author(s):  
Masayuki Takahashi ◽  
Kei Daizumoto ◽  
Megumi Tsuda ◽  
Yoshito Kusuhara ◽  
Hidehisa Mori ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Insulin Receptor ◽  
Cell Carcinoma ◽  
Primary Tumor ◽  
Renal Cell ◽  
Clear Cell ◽  
Advanced Renal Cell Carcinoma ◽  
Second Line ◽  
Gene Set ◽  
Clear Cell Rcc

442 Background: Axitinib has demonstrated high efficacy with well-controlled adverse events (AEs) for advanced renal cell carcinoma (RCC). Recently, nivolumab has been approved for advanced RCC. However, it is very expensive in Japan and may cause severe immune-related AEs. There is no clue to choose axitinib or nivolumab as the second-line for advanced RCC. Previously we identified the gene set which may predict poor prognosis of RCC patients (Takahashi m et.al., Proc Natl Acad Sci U S A., 98: 9754, 2001) and have sought to elucidate whether insulin receptor (INSR) expression in the gene set may predict the resistance for axitinib as a biomarker. Methods: Axitinib was administered in 36 patients in our department between January 2008 and April 2015. Median age was 70 (36-84) years old with 22 males and 14 females. Histological subtype included clear cell RCC (n=27, 75.0%), clear cell + sarcomatoid component (n=3), collecting duct carcinoma (n=2), papillary, sarcomatoid, mucinous tubular and spindle cell carcinoma (MTSCC), and unknown in each one. Axitinib was administered in two patients as the first line, 21 patients as the second line, and 13 patients as ≥ the third line. Tissue of primary tumor was available in 20/36 patients, including 16 clear cell RCC and 4 other subtypes. Immunohistochemical INSR expression was examined and correlated with survival of the patients with axitinib. Results: Objective response rate was 27.6%, progression-free survival (PFS) was 16.3 months, and overall survival (OS) was 41.9 months in clear cell RCC patients. Patients with low INSR expression (n=7) had significantly shorter PFS (68 vs. 586 days, p<0.001) and OS (169 vs. 1027 days, p=0.004) compared with those with high INSR expression (n=13). If only clear cell RCC was evaluated, patients with low INSR expression (n=3) had significantly shorter PFS (77 vs. 586 days, p=0.008) and OS (294 vs. 1027 days, p=0.016) compared with those with high INSR expression (n=13). Conclusions: Axitinib was highly effective for advanced clear cell RCC. However, immunohistochemically low expression of INSR in the primary tumor may predict the resistance for axitinib and those patients may be more suitable for immune checkpoint inhibitors.

Frustration and distress during treatment for advanced renal cell carcinoma.

2018 ◽  
Vol 36 (34_suppl) ◽  
pp. 47-47
Author(s):  
Cristiane Decat Bergerot ◽  
Dena Battle ◽  
Paulo Gustavo Bergerot ◽  
Daniel J. George ◽  
Hans J. Hammers ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Online Survey ◽  
Clear Cell ◽  
Psychosocial Support ◽  
Qualitative Content Analysis ◽  
Advanced Renal Cell Carcinoma ◽  
Cross Sectional ◽  
Common Diagnosis

47 Background: Treatment strategies for advanced renal cell carcinoma (aRCC) have improved over the past 15 years. Durable responses are now achievable, giving rise to the possibility of cure in a small proportion of this population. However, it is not clear how patients are coping with more protracted courses of treatment. We sought to determine sources of frustration among patients diagnosed with aRCC. Methods: We performed a cross-sectional analysis of data derived from an online survey distributed via social media from April to June, 2017. We assessed source of frustration using an open-ended question: “In your own words, what has frustrated you most about your medical care related to your diagnosis?”. We assessed distress using the Distress Thermometer. Qualitative content analysis was performed to characterize responses related to frustration. Descriptive statistics was generated and the Kruskal-Wallis test was used to explore the relationship between clinical characteristics and sources of frustration. Results: We enrolled 217 patients with aRCC. The majority were male (52.3%), and white (93.5%). Clear cell histology (84.2%) was the most common diagnosis. Patients reported high levels of distress (M = 6.4; SD = 2.8). Sources of frustration were documented in 71.9% of patients, and were most commonly related to distrust of the cancer care system (12.4%), fear of progression (11.5%), lack of information (11.1%), financial concerns (9.7%), communication between patient and physician (7.8%), treatment side effects (4.6%), lack of available research (4.1%), mistrust of physician’s knowledge (4.1%), and access to supportive care (2.8%). Higher levels of frustration were associated with higher levels of distress (P = 0.01). Patients with non-clear cell RCC more commonly reported an emotional source of frustration (P = 0.02). Conclusions: Patients with aRCC report high levels of distress and frustration with their diagnosis and treatment. The most frequent drivers of frustration can suggest opportunities to maximize support to patients and their families. A better understanding of their disease and prognosis, addressing financial concerns and offering psychosocial support may alleviate frustration amongst patients with aRCC.

A FavorAx study of axitinib in favorable risk patients with metastatic renal cell carcinoma.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 666-666
Author(s):  
Ilya Tsimafeyeu ◽  
Pavel Borisov ◽  
Ahmed Abdelgafur ◽  
Roman Leonenkov ◽  
Olga Novikova ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Adverse Events ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Primary Endpoint ◽  
Renal Cell ◽  
Response Rate ◽  
Objective Response ◽  
First Line ◽  
History Of

666 Background: Targeted therapy with axitinib resulted in a greater objective response rate and prolonged progression-free survival (PFS) compared to sorafenib in patients with previously treated metastatic renal cell carcinoma (mRCC) in AXIS study. 75% of patients had intermediate and poor IMDC prognosis. In this phase 2 study, we assessed the activity of axitinib in mRCC patients with favourable risk and a history of prior VEGFR-directed therapy. Methods: Patients were required to have clear cell mRCC, favourable risk according to IMDC criteria, and to have received first-line treatment with sunitinib or pazopanib. Prior treatment with other agents was not permitted. The primary endpoint of the study was PFS. Additional endpoints included response rate, safety, and overall survival (OS). Results: A total of 21 patients were enrolled, 62% of whom were male. Median age was 59 years. 11 (52%) patients had 2 and more metastatic sites. 67% and 33% of patients received first-line sunitinib or pazopanib with a median PFS of 17 months (95% CI 14-20). After a median follow-up of 16 months, the median PFS and OS was not yet reached. The current study did achieve its primary endpoint based on the 10-month PFS of 71.4%. 3 (14.3%) patients had confirmed partial responses and 14 (66.7%) had stable disease. No grade 3/4 treatment-related adverse events were observed; the most frequent grade 1/2 treatment-related adverse events were hypertension (57.1%), fatigue (57.1%), GI (33%) and skin (19%) toxicity. 7 patients had dose-escalation of axitinib and 1 patient had dose reduction. Conclusions: The encouraging PFS and favorable safety profile observed in FavorAx study support the administration of axitinib in mRCC patients with favourable IMDC risk and a history of prior sunitinib or pazopanib. Clinical trial information: NCT02700568.

Immune checkpoint inhibitors plus tyrosine kinase inhibitors combination in the first-line setting of metastatic clear cell renal cell carcinoma: A meta-analysis of randomized clinical trials.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 704-704
Author(s):  
Maria Cruz Martin Soberón ◽  
Alberto Carretero-González ◽  
Guillermo de Velasco ◽  
Lucia Carril ◽  
Daniel Castellano
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Subgroup Analysis ◽  
Renal Cell ◽  
Randomized Clinical Trials ◽  
Clear Cell ◽  
Meta Analysis ◽  
Objective Response ◽  
Significant Benefit ◽  
Cell Renal Cell Carcinoma

704 Background: ICIs + TKIs have shown to improve outcomes in treatment-naïve metastatic clear-cell renal cell carcinoma (ccRCC). We aimed to analize the efficacy of all combinations published including the subgroup analysis based on age, sex and IMDC prognostic factors score. Methods: We searched published RCTs in MEDLINE and EMBASE comparing ICIs + TKIs vs TKIs in 1L metastatic ccRCC. Outcomes selected to assess efficacy were progression-free survival (PFS), overall survival (OS) and objective response rate (ORR) in the intent-to-treat population. Hazard ratios (HR) for PFS and OS, and relative risk (RR) for ORR with 95% confidence intervals (CI) were used as efficacy measures. Subgroup-based meta-analysis was afterwards performed according to randomized-effect model. Results: We identified two eligible RCTs of ICIs + TKIs (avelumab [avelu] or pembrolizumab [pembro] + axitinib [axi]) versus TKIs (sunitinib). Combined sample size was 1,747 patients (avelu + axi arm 442 patients; pembro + axi arm 432 patients; sunitinib arm 873 patients). Globally, three outcomes favored the combination. Improved HRs for PFS (0.69), OS (0.64) and ORR (1.81) were found for combination (Table). Regarding subgroup analysis HRs for PFS were favorable for combination in male (0.665) and female (0.66). Benefit in combination arms was confirmed in terms of age < 65 years (0.68) and ≥ 65 years (0.66). Intermediate and poor IMDC subgroups showed statistically significant benefit for combination (HR 0.68 and 0.56), whereas PFS in favorable group (0.68) was not statistically significant. Conclusions: ICIs + TKIs combination therapy has consistently demonstrated to be superior in terms of OS, PFS and ORR in 1L ccRCC to TKIs alone. We hereby confirm statistically significant benefit per subgroups except for favorable IMDC subgroup.[Table: see text]

A phase II study of lenvatinib plus everolimus in patients with advanced non-clear cell renal cell carcinoma (nccRCC).

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 685-685 ◽  
Author(s):  
Thomas E. Hutson ◽  
M Dror Michaelson ◽  
Timothy M. Kuzel ◽  
Neeraj Agarwal ◽  
Ana M. Molina ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Antiangiogenic Therapy ◽  
Objective Response ◽  
Vegf Receptor ◽  
Phase 2 ◽  
Cell Renal Cell Carcinoma ◽  
Once Daily

685 Background: Non-clear cell renal cell carcinoma (nccRCC) is an umbrella term that encompasses multiple RCC histological subtypes, including papillary, chromophobe, and undetermined RCC. Both increased expression of the vascular endothelial growth factor (VEGF) and dysregulation of the mammalian target of rapamycin (mTOR) pathway occur in nccRCC. Lenvatinib (LEN) is a multitarget tyrosine kinase inhibitor that inhibits the VEGF receptor and other targets; everolimus (EVE) is a mTOR inhibitor. LEN + EVE is approved for the treatment of patients with advanced RCC following 1 prior antiangiogenic therapy. This phase 2 study examined the efficacy and tolerability of LEN + EVE in patients with nccRCC. Methods: This single-arm, multicenter, phase 2 trial assessed the safety and efficacy of LEN (18 mg once daily) + EVE (5 mg once daily) in patients with unresectable advanced or metastatic nccRCC who had not received any chemotherapy for advanced disease. The primary objective was objective response rate (ORR) as assessed by investigators using RECIST v1.1. Secondary objectives included progression-free survival (PFS), overall survival (OS), and safety assessments. Results: At the time of data cutoff (July 17, 2019), 31 patients with nccRCC (papillary, n = 20; chromophobe, n = 9; unclassified, n = 2) were enrolled and treated. The ORR was 25.8% (95% confidence interval [CI]: 11.9–44.6%); 8 patients achieved a partial response (PR; papillary, n = 3; chromophobe, n = 4; unclassified, n = 1) and no patients had a complete response (CR). The median duration of response was not reached. Additionally, 18 patients (58.1%) had stable disease (SD) and the clinical benefit rate (CR + PR + durable SD [duration ≥ 23 weeks]) was 61.3% (95% CI: 42.2–78.2%). The median PFS was 9.23 months (95% CI: 5.49- not estimable [NE]) and median OS was 15.64 months (95% CI: 9.23–NE). The safety profile observed in this study was similar to the established profile of the study drug combination (LEN + EVE). Conclusions: The combination of LEN + EVE showed promising antitumor activity as first-line therapy in patients with advanced nccRCC. The ORR was 25.8%, which compares favorably to historical reports with EVE monotherapy. Clinical trial information: NCT02915783.

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.

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