Sunitinib versus sorafenib as first-line therapy followed by sorefenib and sunitinib for patients with metastatic renal cell carcinoma (RCC) with clear cell histology: A multicenter randomized trial, CROSS-J-RCC.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 469-469 ◽  
Author(s):  
Yoshihiko Tomita ◽  
Sei Naito ◽  
Naoto Sassa ◽  
Atsushi Takahashi ◽  
Tsunenori Kondo ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Second Line ◽  
First Line ◽  
Standard Dosage ◽  
Line Therapy ◽  
Significant Difference

469 Background: SWITCH, a prospective, randomized sequential trial to evaluate SU/SO versus SO/SU, revealed no difference in first-line or total PFS or OS, but no direct comparison was obtained between 1st line sunitinib (SU) and sorafenib (SO) for clear cell (CC) metastatic renal cell carcinoma (mRCC). Methods: Treatment-naïve patients with CC mRCC, ECOG PS 0/1 and MSKCC favorable or intermediate risk were randomized to receive open-label SU/SO or SO/SU at the standard dosage and schedule. The primary endpoint was 1st line PFS, and secondary endpoints were total PFS and OS. The calculated sample size was 59 per group, with α = 0.05, β = 0.10, and a censoring rate of 15%. Results: Of 124 patients enrolled in this study from February 2010 to July 2012 from 39 institutions, 120 could be evaluated (SU/SO, 57 and SO/SU, 63). Baseline patients' characteristics in the SU/SO and SO/SU groups were as follows: favorable risk, 21% and 22%; and presence ofnephrectomy, 88% and 89%, respectively. First-line mPFS was 8.7 and 7.0 months in the SU/SO and SO/SU groups, respectively (HR, 0.67; 95% CI, 0.42–1.08; p= 0.095). There was no statistically significant difference in total (T)-PFS, 27.8 M, and 22.6 m (HR 0.73, CI 0.428-1.246; p=0.247), or OS 38.4 m and 30.9 m (HR 0.934, CI 0.588-1.485; p=0.773). Subgroup analyses showed that T-PFS was NR and 27.8 m (p=0.021) in the favorable risk, and 38.4 m and 16.1 m (p=0.009) in with less than 5 metastatic sites, 6.5 m and 13.6 m (p=0.025) without nephrectomy in the SU/SO and SO/SU groups, respectively. The most common adverse events (AEs) in case of first-line SU or SO (all grade, all cause) were hand–foot syndrome (71% vs. 86%), hypothyroidism (70% vs. 33%), fatigue (57% vs. 40%), hypertension (55% vs. 44%), and diarrhea (23% vs. 38%). AEs were generally lower during second-line therapy. Conclusions: There was no significant difference in first-line PFS, T-PFS, and OS between the two sequential treatments. Although fewer patients received second-line treatment in the SU/SO group, OS in this group was numerically longer than that in the SO/SU group. Clinical trial information: 01481870.

Comparison of First-line Pazopanib and Sunitinib in Metastatic Renal Cell Carcinoma: Experiences of the Urologic Cancer Centre for Research and Innovation

2019 ◽  
Author(s):  
Emily C.L. Wong ◽  
Camilla Tajzler ◽  
Gaurav Vasisth ◽  
Amanda Zhu ◽  
Mathilda Chow ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Side Effects ◽  
Cell Carcinoma ◽  
Disease Progression ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Significant Difference

Abstract Background: Sunitinib and pazopanib are orally-administered tyrosine kinase receptor inhibitors (TKIs) approved as first-line therapy for the treatment of metastatic renal cell carcinoma (mRCC). The IMDC criteria are a predictive prognostic model for patients with mRCC when stratified into three prognosis groups: favourable, intermediate and poor. We retrospectively compared the efficacy and safety of sunitinib and pazopanib as first-line therapy for patients with mRCC in our single institution database. Methods: Retrospective analysis was done to compare progression-free survival (PFS) and side effects of sunitinib and pazopanib as first-line therapy in patients with mRCC. Patients were stratified into prognosis groups according to IMDC criteria. Disease assessment was performed on measurable aspects of disease based on computed tomography or magnetic resonance imaging reports. Survival analysis was performed using the Kaplan-Meier method and Cox regression, with disease progression as the endpoint.Results: Data was obtained from 228 patients with mRCC who were treated with either pazopanib (n=57) or sunitinib (n=171). No significant difference in PFS was found between sunitinib and pazopanib (HR for disease progression or all-cause death, 1.10; 95%CI: 0.76-1.57, p=0.62). Median PFS time for patients receiving sunitinib was 9.4 months and for pazopanib, 8.5 months. Median PFS for patients with intermediate-risk disease was similar between groups (9.4 months vs. 9.2 months, respectively, p=0.93). However, patients treated with sunitinib experienced a greater number of side effects compared to pazopanib. Conclusions: Sunitinib and pazopanib are similarly efficacious as first-line therapy for mRCC. However, adverse events are lower with pazopanib.

scholarly journals Stereotactic body radiotherapy in combination with non-frontline PD-1 inhibitors and targeted agents in metastatic renal cell carcinoma

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Yang Liu ◽  
Zhiling Zhang ◽  
Ruiqi Liu ◽  
Wensu Wei ◽  
Zitong Zhang ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Stereotactic Body Radiotherapy ◽  
Renal Cell ◽  
Clear Cell ◽  
Targeted Agents ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy

Abstract Background Radiotherapy may work synergistically with immunotherapy and targeted agents. We aimed to assess the safety and outcomes of stereotactic body radiotherapy (SBRT) plus non-first-line programmed death-1 (PD-1) inhibitors and targeted agents (TA) in metastatic renal cell carcinoma (mRCC). Methods We retrospectively reviewed 74 patients treated with non-first-line PD-1 inhibitors plus TA in non-first-line setting. Survival outcomes were calculated from the anti-PD-1 treatment using the Kaplan–Meier method. Univariate and multivariate analyses were performed by Cox proportional hazards models. Results Thirty-two (43.2%) patients received anti-PD-1/TA therapy alone (anti-PD-1/TA alone group), and 42 (56.8%) received SBRT in addition (anti-PD-1/TA + SBRT group). The median duration of first-line therapy was 8.6 months. Patients in the anti-PD-1/TA + SBRT group had significantly longer overall survival (OS) (38.5 vs 15.4 months; P = 0.022). On multivariate analysis, oligometastasis, ECOG performance status 0–1, anti-PD-1/TA + SBRT, and duration of first-line therapy ≥ 8.6 months were predictors for OS. The addition of SBRT was associated with improved OS in patients with clear-cell type (HR 0.19; 95% CI 0.07–0.55; P = 0.002) and duration of first-line therapy ≥ 8.6 months (HR 0.22; 95% CI 0.06–0.88; P = 0.032). Grade ≥ 3 toxicities occurred in 23 patients (54.8%) in the anti-PD-1/TA + SBRT group, and in 21 patients (65.6%) in the anti-PD-1/TA alone group. Conclusions Incorporating SBRT into anti-PD-1/TA therapy is safe and tolerable. Further investigation is needed, particularly in patients with clear-cell histology and a longer duration of response to first-line antiangiogenic therapy.

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 Outcomes from second-line therapy in long-term responders to first-line tyrosine kinase inhibitor in clear-cell metastatic renal cell carcinoma

2015 ◽  
Vol 26 (2) ◽  
pp. 378-385 ◽  
Author(s):  
R. Elaidi ◽  
A. Harbaoui ◽  
B. Beuselinck ◽  
J.-C. Eymard ◽  
A. Bamias ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Kinase Inhibitor ◽  
Clear Cell ◽  
Second Line ◽  
First Line ◽  
Second Line Therapy ◽  
Line Therapy

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]

scholarly journals Randomized Phase III Trial of Temsirolimus Versus Sorafenib As Second-Line Therapy After Sunitinib in Patients With Metastatic Renal Cell Carcinoma

2014 ◽  
Vol 32 (8) ◽  
pp. 760-767 ◽  
Author(s):  
Thomas E. Hutson ◽  
Bernard Escudier ◽  
Emilio Esteban ◽  
Georg A. Bjarnason ◽  
Ho Yeong Lim ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Phase Iii ◽  
Second Line ◽  
Second Line Therapy ◽  
Phase Iii Trial ◽  
Line Therapy

Purpose This international phase III trial (Investigating Torisel As Second-Line Therapy [INTORSECT]) compared the efficacy of temsirolimus (mammalian target of rapamycin inhibitor) and sorafenib (vascular endothelial growth factor receptor [VEGFR] tyrosine kinase inhibitor) as second-line therapy in patients with metastatic renal cell carcinoma (mRCC) after disease progression on sunitinib. Patients and Methods In total, 512 patients were randomly assigned 1:1 to receive intravenous temsirolimus 25 mg once weekly (n = 259) or oral sorafenib 400 mg twice per day (n = 253), with stratification according to duration of prior sunitinib therapy (≤ or > 180 days), prognostic risk, histology (clear cell or non–clear cell), and nephrectomy status. The primary end point was progression-free survival (PFS) by independent review committee assessment. Safety, objective response rate (ORR), and overall survival (OS) were secondary end points. Results Primary analysis revealed no significant difference between treatment arms for PFS (stratified hazard ratio [HR], 0.87; 95% CI, 0.71 to 1.07; two-sided P = .19) or ORR. Median PFS in the temsirolimus and sorafenib arms were 4.3 and 3.9 months, respectively. There was a significant OS difference in favor of sorafenib (stratified HR, 1.31; 95% CI, 1.05 to 1.63; two-sided P = .01). Median OS in the temsirolimus and sorafenib arms was 12.3 and 16.6 months, respectively. Safety profiles of both agents were consistent with previous studies. Conclusion In patients with mRCC and progression on sunitinib, second-line temsirolimus did not demonstrate a PFS advantage compared with sorafenib. The longer OS observed with sorafenib suggests sequenced VEGFR inhibition may benefit patients with mRCC.

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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