scholarly journals Optimal first-line and second-line treatments for metastatic renal cell carcinoma: current evidence

2014 ◽  
pp. 401 ◽  
Author(s):  
Maxine Sun ◽  
Alessandro Larcher ◽  
Pierre Karakiewicz
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Current Evidence ◽  
Second Line ◽  
First Line

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.

Second-line VEGF TKI after IO combination therapy: Results from the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC).

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 684-684
Author(s):  
Igor Stukalin ◽  
Shaan Dudani ◽  
Connor Wells ◽  
Chun Loo Gan ◽  
Sumanta K. Pal ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Combination Therapy ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Cox Regression ◽  
Response Rates ◽  
Second Line ◽  
First Line ◽  
Cox Regression Analysis

684 Background: Immuno-Oncology (IO) combinations are standard of care first-line treatment for metastatic renal cell carcinoma (mRCC). Data on therapy with vascular endothelial growth factor (VEGF) tyrosine kinase inhibitors (TKI) post-progression on IO-combination therapy are limited. Methods: Using the IMDC, a retrospective analysis was done on mRCC patients treated with second-line VEGF TKIs after receiving IO combination therapy. Patients received first-line ipilimumab+nivolumab (IOIO) or anti-PD(L)1+anti-VEGF (IOVE). Baseline variables and second-line IMDC risk factors were collected. Overall response rates (ORR), time to treatment failure (TTF) and overall survival (OS) were determined. Multivariable Cox regression analysis was performed. Results: 142 patients were included. 75 patients received IOIO and 67 received IOVE pretreatment. The ORR of 2nd line therapy was 17/46 (37%) and 7/57 (12%) in the IOIO and IOVE pretreated groups, respectively (p<0.01). 2nd-line TTF was 5.4 months (95% CI 4.1-8.3) for the IOIO- and 4.6 months (95% CI 3.7-5.8) for the IOVE-pretreated group (p=0.37). 2nd-line median OS was 17.2 months (95% CI 10.8-35.1) and 11.8 months (95% CI 9.9-21.3) for the prior IOIO and IOVE groups, respectively (p=0.13). The hazard ratio adjusted by IMDC for IOVE vs IOIO pretreatment was 1.22 (95% CI 0.73-2.07, p=0.45) for 2nd line TTF and 1.43 (95% CI 0.74-2.8, p=0.29) for 2nd line OS. Conclusions: VEGF TKIs show activity after combination IO therapy. Response rates are higher in patients treated with VEGF TKIs after first-line IOIO compared to after IOVE. In patients with VEGF TKI after IOIO or IOVE, no difference in OS and TTF was observed.[Table: see text]

scholarly journals STUDY OF THE EFFECTIVENESS OF TARGETED THERAPY IN METASTATIC RENAL CELL CARCINOMA PATIENTS

2017 ◽  
Vol 22 (3) ◽  
pp. 136-141
Author(s):  
Galina N. Alekseeva ◽  
L. I Gurina ◽  
M. V Volkov ◽  
E. V Evtuchenko
Keyword(s):  
Renal Cell Carcinoma ◽  
Targeted Therapy ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Second Line ◽  
First Line ◽  
Favorable Prognosis ◽  
The One ◽  
Optimal Approach

Objective. To study the relapse-free overall survival in metastatic renal cell carcinoma (mRCC) patients after the targeted therapy and to develop optimal approach to the treatment shedule. Material and methods. The research included 88 mRCC patients of mean age of 55.5 + 9.6 years, 63 (71.6%) men and 25 (28.4%) women. 42.0% patients had a favorable prognosis, 52.3% - intermediate one and 5.7% of the cases had poor prognosis. First line targeted therapy was carried out in 88 patients, the second line - in 26 patients, and the third line - in 7 patients. Results. The one or several lines of targeted therapy allowed to achieve 20 months of a median in survival without progression of the disease. Several lines of treatment increased a median of general survival up to 42 months in comparison with the patients who were involved in the one line of treatment (a median = 30 months), p = 0.001. Side effects of targeted therapy were reversible. In the first line targeted therapy the preference was given to sunitinib, in the second line - to sorafenib. Sorafenib had an advantage in case of not light-cellular forms of renal carcinoma. In cases with favorable prognosis factors, metastases into organ parenchyma, targeted therapy with bevacizumab was carried out.

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]

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.

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