Survival comparison analysis of two historical cohorts of metastatic renal cell carcinoma patients (cytokine therapy versus targeted agents): A European single-center experience over 26 years.

513 Background: By the approval of new targeted agents in 2006, the standard of therapy in metastatic renal cell carcinoma (mRCC) changed, since they demonstrated significantly improved progression-free survival (PFS) rates compared with interferon in phase III clinical trials. Differences in overall survival (OS) could not be proven since many patients switched to another effective substance after progression of the disease. Thus, we compared two mRCC patient cohorts in order to detect OS differences between immunotherapy and targeted therapies in a real-life population outside controlled clinical trials. Methods: Clinico-pathological data from 594 mRCC patients, operated between 1984 and 2010 at a single tertiary academic center, were evaluated retrospectively with the null hypothesis, that there is no statistically significant difference in OS of patients treated either with interferon or targeted agents. Using electronical patient records, all data regarding the beginning, duration, lines, and different forms of therapies were assessed. Patients’ cancer-specific survival (CSS), as well as OS, were assessed using the Kaplan-Meier method, compared with the log-rank test. A first analysis revealed results for the entire study cohort. Subsequently, outcome analyses were restricted to mRCC patients with clear cell histology only. Results: With respect to the complete follow-up period, our results in both analyses did not show a statistically significant OS difference between the two therapy modalities. By limiting the observation period to 5 years after treatment initiation, a statistically significantly improved median five-year OS rate (26 mo.) for clear cell mRCC patients treated with targeted agents was observed, compared with 21 mo. in the interferon group (p=0.028). Conclusions: Our results confirm the presumption of an improved OS in mRCC attributable to treatments with targeted agents compared with previous cytokine therapies.

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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.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.6_suppl.469 ◽

2017 ◽

Vol 35 (6_suppl) ◽

pp. 469-469 ◽

Cited By ~ 5

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.

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Randomized Phase III Trial of Temsirolimus and Bevacizumab Versus Interferon Alfa and Bevacizumab in Metastatic Renal Cell Carcinoma: INTORACT Trial

Journal of Clinical Oncology ◽

10.1200/jco.2013.50.5305 ◽

2014 ◽

Vol 32 (8) ◽

pp. 752-759 ◽

Cited By ~ 134

Author(s):

Brian I. Rini ◽

Joaquim Bellmunt ◽

Jill Clancy ◽

Kongming Wang ◽

Andreas G. Niethammer ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Combination Therapy ◽

Cell Carcinoma ◽

Metastatic Renal Cell Carcinoma ◽

Renal Cell ◽

Clear Cell ◽

Objective Response ◽

Interferon Alfa ◽

Phase Iii ◽

Cancer Center

PurposeTo prospectively determine the efficacy of combination therapy with temsirolimus plus bevacizumab versus interferon alfa (IFN) plus bevacizumab in metastatic renal cell carcinoma (mRCC).Patients and MethodsIn a randomized, open-label, multicenter, phase III study, patients with previously untreated predominantly clear-cell mRCC were randomly assigned, stratified by prior nephrectomy and Memorial Sloan-Kettering Cancer Center prognostic group, to receive the combination of either temsirolimus (25 mg intravenously, weekly) or IFN (9 MIU subcutaneously thrice weekly) with bevacizumab (10 mg/kg intravenously, every 2 weeks). The primary end point was independently assessed progression-free survival (PFS).ResultsMedian PFS in patients treated with temsirolimus/bevacizumab (n = 400) versus IFN/bevacizumab (n = 391) was 9.1 and 9.3 months, respectively (hazard ratio [HR], 1.1; 95% CI, 0.9 to 1.3; P = .8). There were no significant differences in overall survival (25.8 ν 25.5 months; HR, 1.0; P = .6) or objective response rate (27.0% ν 27.4%) with temsirolimus/bevacizumab versus IFN/bevacizumab, respectively. Patients receiving temsirolimus/bevacizumab reported significantly higher overall mean scores in the Functional Assessment of Cancer Therapy–Kidney Symptom Index (FKSI) –15 and FKSI-Disease Related Symptoms subscale compared with IFN/bevacizumab (indicating improvement); however, no differences in global health outcome measures were observed. Treatment-emergent all-causality grade ≥ 3 adverse events more common (P < .001) with temsirolimus/bevacizumab were mucosal inflammation, stomatitis, hypophosphatemia, hyperglycemia, and hypercholesterolemia, whereas neutropenia was more common with IFN/bevacizumab. Incidence of pneumonitis with temsirolimus/bevacizumab was 4.8%, mostly grade 1 or 2.ConclusionTemsirolimus/bevacizumab combination therapy was not superior to IFN/bevacizumab for first-line treatment in clear-cell mRCC.

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

Radiation Oncology ◽

10.1186/s13014-021-01937-9 ◽

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.

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Indirect comparisons of efficacy and safety between seven newer targeted agents for metastatic renal cell carcinoma: A network meta-analysis of randomised clinical trials

Molecular and Clinical Oncology ◽

10.3892/mco.2014.323 ◽

2014 ◽

Vol 2 (5) ◽

pp. 858-864 ◽

Cited By ~ 10

Author(s):

HENRY W.C. LEUNG ◽

AGNES L.F. CHAN ◽

SHUN-JEN LIN

Keyword(s):

Renal Cell Carcinoma ◽

Clinical Trials ◽

Cell Carcinoma ◽

Metastatic Renal Cell Carcinoma ◽

Renal Cell ◽

Meta Analysis ◽

Randomised Clinical Trials ◽

Targeted Agents ◽

Efficacy And Safety ◽

Indirect Comparisons

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Treatment Outcome and Survival Associated With Metastatic Renal Cell Carcinoma of Non–Clear-Cell Histology

Journal of Clinical Oncology ◽

10.1200/jco.2002.11.123 ◽

2002 ◽

Vol 20 (9) ◽

pp. 2376-2381 ◽

Cited By ~ 349

Author(s):

Robert J. Motzer ◽

Jennifer Bacik ◽

Tania Mariani ◽

Paul Russo ◽

Madhu Mazumdar ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Clinical Trials ◽

Cell Carcinoma ◽

Metastatic Renal Cell Carcinoma ◽

Renal Cell ◽

Clear Cell ◽

Collecting Duct ◽

Outcome Data ◽

Number Of Patients ◽

Clear Cell Rcc

PURPOSE: To define outcome data for patients with metastatic renal cell carcinoma (RCC) with histology other than clear-cell type, including collecting duct (or medullary carcinoma), papillary, chromophobe, and unclassified histologies. PATIENTS AND METHODS: Sixty-four patients with metastatic non–clear-cell RCC histology were the subjects of this retrospective review. Included in the analysis were 22 (8%) of 286 patients from a clinical trials database, 19 of 1,166 patients from a surgery database, and 23 of 357 patients from a pathology database. RESULTS: The prevalent histology was collecting duct, present in 26 (41%) patients. The number of patients with chromophobe and papillary histologies was 12 (19%) and 18 (28%), respectively. Eight (12%) of the patients had tumors that could not be classified for specific tumor histology. Among the 43 patients treated with 86 systemic therapies, including 37 cytokine therapies, two patients (5%) were observed to have a partial response. The median overall survival time was 9.4 months (95% confidence interval, 8 to 14 months). The survival was longer for patients with chromophobe tumors compared with collecting duct or papillary histology, and this group included four patients with survival of greater than 3 years. CONCLUSION: RCC consists of a heterogeneous group of tumors including clear-cell, papillary, chromophobe, collecting duct, and unclassified cell types. Non–clear-cell histologies constitute less than 10% of patients in general populations of patients with advanced RCC treated on clinical trials. Metastatic non–clear-cell RCC is characterized by a resistance to systemic therapy and poor survival, with the survival for patients with chromophobe tumors longer than that for patients with metastatic collecting duct or papillary RCC. Treatment with novel agents on clinical trials is warranted.

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

Journal of Clinical Oncology ◽

10.1200/jco.2013.50.3961 ◽

2014 ◽

Vol 32 (8) ◽

pp. 760-767 ◽

Cited By ~ 248

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.

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