scholarly journals Phase II Randomized Trial Comparing Sequential First-Line Everolimus and Second-Line Sunitinib Versus First-Line Sunitinib and Second-Line Everolimus in Patients With Metastatic Renal Cell Carcinoma

2014 ◽  
Vol 32 (25) ◽  
pp. 2765-2772 ◽  
Author(s):  
Robert J. Motzer ◽  
Carlos H. Barrios ◽  
Tae Min Kim ◽  
Silvia Falcon ◽  
Thomas Cosgriff ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Phase Ii ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Progression Free Survival ◽  
Primary Objective ◽  
Second Line ◽  
First Line ◽  
First Line Therapy

Purpose A multicenter, randomized phase II trial, RECORD-3, was conducted to compare first-line everolimus followed by sunitinib at progression with the standard sequence of first-line sunitinib followed by everolimus in patients with metastatic renal cell carcinoma. Patients and Methods RECORD-3 used a crossover treatment design. The primary objective was to assess progression-free survival (PFS) noninferiority of first-line everolimus compared with first-line sunitinib. Secondary end points included combined PFS for each sequence, overall survival (OS), and safety. Results Of 471 enrolled patients, 238 were randomly assigned to first-line everolimus followed by sunitinib, and 233 were randomly assigned to first-line sunitinib followed by everolimus. The primary end point was not met; the median PFS was 7.9 months for first-line everolimus and 10.7 months for first-line sunitinib (hazard ratio [HR], 1.4; 95% CI, 1.2 to 1.8). Among patients who discontinued first-line, 108 (45%) crossed over from everolimus to second-line sunitinib, and 99 (43%) crossed over from sunitinib to second-line everolimus. The median combined PFS was 21.1 months for sequential everolimus then sunitinib and was 25.8 months for sequential sunitinib then everolimus (HR, 1.3; 95% CI, 0.9 to 1.7). The median OS was 22.4 months for sequential everolimus and then sunitinib and 32.0 months for sequential sunitinib and then everolimus (HR, 1.2; 95% CI, 0.9 to 1.6). Common treatment-emergent adverse events during first-line everolimus or sunitinib were stomatitis (53% and 57%, respectively), fatigue (45% and 51%, respectively), and diarrhea (38% and 57%, respectively). Conclusion Everolimus did not demonstrate noninferiority compared with sunitinib as a first-line therapy. The trial results support the standard treatment paradigm of first-line sunitinib followed by everolimus at progression.

First-line sunitinib versus pazopanib in metastatic renal cell carcinoma (mRCC): Results from the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC).

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 544-544 ◽  
Author(s):  
Jose Manuel Ruiz Morales ◽  
J Connor Wells ◽  
Frede Donskov ◽  
Georg A. Bjarnason ◽  
Jae-Lyun Lee ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Progression Free Survival ◽  
Similar Efficacy ◽  
Phase Iii ◽  
Line Treatment ◽  
Second Line ◽  
First Line

544 Background: Sunitinib (SU) and Pazopanib (PZ) have been compared head-to-head in the first-line phase III COMPARZ study in metastatic renal cell carcinoma (mRCC). We compared SU versus PZ, to confirm outcomes and subsequent second-line therapy efficacy in a population-based setting. Methods: We used the IMDC to assess overall survival (OS), progression-free survival (PFS), response rate (RR) and performed proportional hazard regression adjusting for IMDC prognostic groups. Second-line OS2 and PFS2 were also evaluated. Results: We obtained data from 3,606 patients with mRCC treated with either first line SU (n=3226) or PZ (n=380) with an overall median follow-up of 43.5 months (m) (CI95% 41.4 – 46.4). IMDC risk group distribution for favorable prognosis was 440 (17.3%) for SU vs 72 (25%) for PZ, intermediate prognosis 1414 (55.6%) for SU vs 153 (53%) for PZ, poor prognosis 689 (27.1%) for SU vs 62 (22%) for PZ, p= 0.0027. We found no difference between SU vs. PZ for OS (20.1 [CI95% 18.76-21.42] vs. 23.68 m [CI95% 19.54 - 28.81] p=0.19), PFS (7.22 [CI95% 6.76 - 7.78] vs. 6.83 m [CI95% 5.58 - 8.27] p=0.49). The RR was similar in both groups (Table 1). Adjusted HR for OS and PFS were 0.952 (CI95% 0.788 – 1.150 p=0.61) and 1.052 (CI95% 0.908 – 1.220 p = 0.49), respectively. We also found no difference in any second-line treatment between either post-SU vs. post-PZ groups for OS2 (12.88 [CI95% 11.89 – 14.19] vs. 12.91 m [CI95% 10.3 – 19.1] p=0.47) and PFS2 (3.67 [CI95% 3.38 – 3.87] vs. 4.53 m [CI95% 3.08 – 5.35] p=0.4). There was no statistical difference in OS2 and PFS2 if everolimus was used after SU or PZ (p = 0.33 and p = 0.41, respectively) or if axitinib was used after SU or PZ (p = 0.73 and p = 0.72, respectively). Conclusions: We confirmed in real world practice, that SU and PZ have similar efficacy in the first-line setting for mRCC and do not affect outcomes with subsequent second-line treatment. [Table: see text]

Phase II trial of combination interferon-alpha and thalidomide as first-line therapy in metastatic renal cell carcinoma

Urology ◽  
2004 ◽  
Vol 63 (6) ◽  
pp. 1061-1065 ◽  
Author(s):  
Peter E. Clark ◽  
M.Craig Hall ◽  
Antonius Miller ◽  
Kevin P. Ridenhour ◽  
Diana Stindt ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Interferon Alpha ◽  
Phase Ii ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Phase Ii Trial ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy

Treatment-related deterioration of renal function as a biomarker to predict antitumor efficacy of sunitinib in patients with metastatic renal cell carcinoma.

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 502-502
Author(s):  
Hironori Fukuda ◽  
Tsunenori Kondo ◽  
Kenji Omae ◽  
Toshio Takagi ◽  
Kazunari Tanabe
Keyword(s):  
Renal Cell Carcinoma ◽  
Renal Function ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Progression Free Survival ◽  
Risk Groups ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy

502 Background: Some on-target adverse events such as hypertension or thrombocytopenia have been reported as biomarkers predicting the efficacy of sunitinib as first-line therapy for patients with metastatic renal cell carcinoma (mRCC). Decrease of renal function is a major adverse event of sunitinib. However, it remains unclear whether the degree of deterioration of renal function can predict the anti-tumor efficacy of sunitinib. We investigated the relationship between treatment-related deterioration of renal function and anti-tumor efficacy in mRCC patients treated with sunitinib. Methods: We retrospectively reviewed the medical records of mRCC patients who were treated with sunitinib for more than 3 months. Patients receiving hemodialysis before receiving sunitinib as well as those who did not undergo nephrectomy were excluded from our analysis. Renal function was evaluated by the estimated glomerular filtration rate (eGFR) calculated using the MDRD equation modified for Japanese patients. The degree of deterioration in eGFR was compared with progression-free survival (PFS). Results: Sixty-two patients were enrolled, the median age was 65 years, and 44 patients (71%) were male. The median baseline eGFR was 49.1 ml/min/1.73m2, and median decrease of eGFR was 9.9 ml/min/1.73m2. Forty-seven patients (76%) had a decreased eGFR of more than 10% compared to baseline values. The patients showing this decrease had significantly longer PFS than those who did not (PFS: 15.5 months vs. 6.1 months, respectively; p=0.001). On multivariate analysis, a decrease in eGFR of more than 10% was a significant independent factor for predicting longer PFS (hazard ratio, 0.37; 95% confidence interval, 0.17-0.83; p=0.017) as well as MSKCC risk groups and cycles of sunitinib. Conclusions: Treatment-related deterioration of renal function is a biomarker to predict better treatment efficacy for use of sunitinib during first-line therapy for patients with mRCC.

scholarly journals Clinical outcomes of the sequential use of pazopanib followed by everolimus for the treatment of metastatic renal cell carcinoma: A multicentre study in Korea

2017 ◽  
Vol 12 (1) ◽  
pp. E15-20 ◽  
Author(s):  
Jeong Ho Kim ◽  
Wan Lee ◽  
Tae Nam Kim ◽  
Jong Kil Nam ◽  
Tae Hyo Kim ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Targeted Therapy ◽  
Cell Carcinoma ◽  
Clinical Outcomes ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Progression Free Survival ◽  
Second Line ◽  
First Line ◽  
Risk Criteria

Introduction: The aim of this study was to investigate the real-world clinical outcomes of first-line pazopanib and second-line everolimus in Korean patients with metastatic renal cell carcinoma (mRCC).Methods: Data of patients who had mRCC with clear-cell component between 2001 and 2015 at multiple institutions were collected retrospectively. To be included in the analysis, patients had to meet the following criteria: age ≥18 years; received first-line targeted therapy with pazopanib; and received second-line targeted therapy with everolimus. The primary outcomes included overall survival (OS), progression-free survival (PFS), and adverse events (AEs).Result: A total of 36 patients were included in the analysis. The median followup period was 33.5 months (range 17‒49.5). The median PFS was eight months (95% confidence interval [CI] 6.4‒9.6) after treatment with pazopanib and three months (95% CI 1.9‒4.1) with everolimus. The median OS was 27 months (95% CI 16.6‒37.4). The median treatment duration was seven months (range 4.3‒10.8) after treatment with pazopanib and 3.5 months (range 3‒4) with everolimus. Multivariate analysis revealed that the Heng risk criteria were independently associated with OS (p<0.001). Almost every patient experienced some form of AE, the majority of which were mostly mild or moderate in severity. The most common AEs were diarrhea (50%), hypertension (44.4%), and fatigue (41.7%) after treatment with pazopanib, and anemia (47.2%), stomatitis (41.7%), and fatigue (38.9%) with everolimus.Conclusions: The outcomes for the patients treated with pazopanib followed by everolimus in Korea as observed by us were consistent with those reported by previous studies. The Heng risk criteria were significantly associated with the prognosis of patients with mRCC. AEs were mainly mild to moderate and readily managed.

Real world outcomes of nivolumab and cabozantinib in metastatic renal cell carcinoma: Results from the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC).

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 615-615 ◽  
Author(s):  
Igor Stukalin ◽  
J Connor Wells ◽  
Jeffrey Graham ◽  
Takeshi Yuasa ◽  
Benoit Beuselinck ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Real World ◽  
Renal Cell ◽  
Phase Iii ◽  
Second Line ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy

615 Background: The immuno-oncology (IO) checkpoint inhibitor nivolumab and the tyrosine kinase inhibitor (TKI) cabozantinib have both been shown in phase III clinical trials to be effective in metastatic renal cell carcinoma (mRCC) after progression on first-line therapy. We sought to explore the real-world efficacy of these therapies in second-line mRCC. Methods: Using the IMDC database, a retrospective analysis was performed on mRCC patients treated with second-line nivolumab or cabozantinib. Baseline characteristics and IMDC risk factors were collected. Overall survival (OS), time to treatment failure (TTF), and response rates were determined for each therapy. Multivariable Cox regression analysis was performed to determine survival differences. Results: 225 patients were treated with nivolumab and 53 with cabozantinib. There was no significant difference in OS identified, with a mOS for nivolumab of 22.1 months (95% CI 17.18 – NR) and 23.7 months (95% CI 15.52 vs. NR) for cabozantinib, p = 0.6053. The TTF was also similar, with 6.90 months (95% CI 4.60 – 9.20) for nivolumab versus 7.39 months (95% CI 5.52 – 12.85) for cabozantinib, p = 0.1983. The adjusted hazard ratio (HR) for nivolumab vs. cabozantinib was 1.297 (95% CI – 0.728 – 2.312), p = 0.3775. Conclusions: Nivolumab and cabozantinib appear to have similar efficacy in terms of OS and TTF in this real-world patient population, thus both novel agents are reasonable therapeutic options for patients progressing after initial first-line therapy. [Table: see text]

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.

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