A phase II study of alternative sunitinib scheduling in patients with metastatic renal cell carcinoma.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 533-533 ◽  
Author(s):  
Eric Jonasch ◽  
Rebecca Slack ◽  
Daniel M. Geynisman ◽  
Matthew I. Milowsky ◽  
Kimryn Rathmell ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Study Drug ◽  
Progression Free Survival ◽  
Primary Objective ◽  
Free Survival ◽  
Grade 3 ◽  
Endpoint Data

533 Background: Sunitinib is an oral antiangiogenic agent indicated for the treatment of metastatic renal cell carcinoma (mRCC). Sunitinib is given in a 4 week on, 2 week off (4/2) schedule. Significant toxicities are observed in patients in the 3rd and 4thweeks of therapy. We hypothesized that a 2 week on, 1 week off (2/1) schedule would provide improved toxicity without compromising efficacy. Methods: A multicenter, single arm study was performed, with all patients initiating sunitinib 50mg on a 2/1 schedule. Schedule and dose alterations were performed if grade > 3 toxicities were observed. The primary objective was to determine the percentage of patients who experienced grade > 3 fatigue, diarrhea, or HFS. The sample size of 60 patients was selected to ensure that the upper bound of a 95% confidence would fall below the standard schedule rate of 25%-30% if the sample rate was 10%-15%, respectively. Secondary outcomes included response rate (RR), progression free survival (PFS), and dose reductions. Results: Between August 2014 and April 2016, a total of 60 patients were enrolled, and 59 were treated. Patients had a median age of 65.5 years (ranging from 45-92). 24% of patients (14/59) had grade 3 or higher fatigue, diarrhea, or HFS (95% CI: 13.6%, 36.6%). This is similar to the average of the 4 week on, 2 week off schedule of 25%-30%, and the lower bound of the confidence interval is in the center of our target rate of 10%-15%. Among events that are at least possibly related to study drug, patients were most likely to experience the expected events of diarrhea (75% with 5 grade 3 events), fatigue (71% with 6 grade 3 events), and HFS (54% with 3 grade 3 events). 22 (37%) patients responded (25.0%, 50.9%). Among patients with secondary endpoint data available, median PFS was 19.3 months (95% CI: 8.2, NR) and 33/56 (59%) of patients underwent dose reduction. Conclusions: Sunitinib administered in a 2/1 schedule in this study did not result in a lower rate of grade 3 or higher fatigue, diarrhea, or HFS when compared to historical data from trials employing a 4/2 schedule. Efficacy data were comparable to studies employing a 4/2 schedule. Clinical trial information: NCT02060370.

Treatment-free survival after discontinuation of immuno-checkpoint therapy, and outcome of subsequent molecular targeted therapy: Retrospective study of Japanese metastatic renal cell carcinoma patients (after I-O study).

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 677-677
Author(s):  
Yoshihiko Tomita ◽  
Go Kimura ◽  
Satoshi Fukasawa ◽  
Yutaka Sugiyama ◽  
Kazuyuki Numakura ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Progression Free Survival ◽  
Free Survival ◽  
Primary Endpoints ◽  
Secondary Endpoints ◽  
Grade 3

677 Background: Guidelines for treatment of metastatic renal cell carcinoma (mRCC) recommend nivolumab monotherapy (NIVO) for treated mRCC, and nivolumab + ipilimumab combination therapy (NIVO+IPI) for untreated IMDC intermediate and poor risk mRCC patients. Though molecular targeted therapies (TTs) such as VEGFR-TKIs and mTORi are recommended as subsequent therapy after NIVO or NIVO+IPI, their impact is still unclear. Methods: Japanese mRCC patients treated with TT after NIVO (CheckMate 025) or NIVO+IPI (CheckMate 214) were retrospectively analyzed. Primary endpoints were investigator assessed ORR of the first TT after NIVO, and after NIVO+IPI. Secondary endpoints included treatment-free survival (TFS) after discontinuation of NIVO and NIVO+IPI, and progression-free survival (PFS) and safety of the first subsequent TT after NIVO and NIVO+IPI. Results: Twenty-six patients of CheckMate 025 and 19 patients of CheckMate 214 from 20 centers in Japan were analyzed. Median TFS after ICI discontinuation was 1.0m and 2.5m for CheckMate 025 and CheckMate 214 patients, respectively. Median follow-up period from the start of TT after ICI discontinuation to date of analysis or death was 22.1m for CheckMate 025, and 20.3m for CheckMate 214 patients. As the first subsequent TT after NIVO or NIVO+IPI, axitinib was the most treated therapy for both CheckMate 025 (53.8%) and CheckMate 214 (47.4%) patients. ORR of TT after NIVO and NIVO+IPI was 26.9% and 31.6%, and median PFS was 8.9m and 16.3m, respectively. During the treatment of first TT after NIVO and NIVO+IPI, 98% percent experienced treated-related adverse events, 51% experienced grade 3-4, but no treatment related death. Conclusions: TTs have favorable antitumor activity for mRCC after NIVO and NIVO+IPI, possibly by changing the mode of action. Safety signals of TTs after ICI were similar to the previous reports. These results indicate sequential TTs after ICI may contribute for durable survival benefit.

Phase II presurgical study of bevacizumab plus erlotinib in untreated patients with metastatic renal cell carcinoma

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 5004-5004
Author(s):  
E. Jonasch ◽  
D. Tsavachdidou ◽  
C. G. Wood ◽  
S. F. Matin ◽  
P. G. Corn ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Phase Ii ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Performance Status ◽  
Study Drug ◽  
Progression Free Survival ◽  
Cancer Center ◽  
Free Survival

5004 Background: The safety and efficacy of presurgical bevacizumab in patients with metastatic renal cell carcinoma (mRCC) is not known. The current study was designed to answer these clinical questions, and to define predictive tissue biomarkers using nephrectomy specimens from patients on trial. Methods: Patients with newly diagnosed clear cell mRCC whose primary tumor was considered resectable were enrolled. In this single arm phase II trial, patients received bevacizumab plus erlotinib or bevacizumab alone for 8 weeks, followed by restaging. Primary endpoint was progression free survival (PFS). If patients demonstrated progressive disease and had a declining performance status after eight weeks, nephrectomy was deferred. Postoperatively, patients continued on study drug(s) if disease stabilization or regression had occurred. Reverse phase protein arrays (RPPAs) were generated from nephrectomy specimens. Results: Between March 2005 and March 2008, 52 patients were enrolled on the study, and 50 were included in the analysis. By the Memorial Sloan-Kettering Cancer Center criteria, 82% of patients had intermediate-risk, and 18% had poor-risk features. Twenty-three patients received bevacizumab plus erlotinib, and 27 received bevacizumab alone. Forty-two patients underwent nephrectomy. Median progression-free survival was 11.0 months (95% CI: 5.5, 15.6 months). Median overall survival was 25.4 months (95% CI 11.4, not estimable). Two perioperative deaths occurred, and neither was attributable to study drug. Wound dehiscence resulted in treatment discontinuation for three patients. RPPA analysis demonstrated a clear separation of better versus worse responding patients. Conclusions: Presurgical treatment with bevacizumab therapy is relatively safe and yields clinical outcomes comparable to post surgical treatment with antivascular therapy in patients with mRCC. Prospective randomized trials testing the use of presurgical therapy to select appropriate patients for cytoreductive nephrectomy are warranted. [Table: see text]

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.

A Phase II Study of Intermittent Sunitinib in Previously Untreated Patients With Metastatic Renal Cell Carcinoma

2017 ◽  
Vol 35 (16) ◽  
pp. 1764-1769 ◽  
Author(s):  
Moshe C. Ornstein ◽  
Laura S. Wood ◽  
Paul Elson ◽  
Kimberly D. Allman ◽  
Jennifer Beach ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Objective Response ◽  
Evaluation Criteria ◽  
Progression Free Survival ◽  
Initial Therapy ◽  
Primary Objective ◽  
Intermittent Therapy

Purpose Sunitinib is a standard initial therapy in metastatic renal cell carcinoma (mRCC), but chronic dosing requires balancing toxicity with clinical benefit. The feasibility and clinical outcome with intermittent sunitinib dosing in patients with mRCC was explored. Patients and Methods Patients with treatment-naïve, clear cell mRCC were treated with four cycles of sunitinib (50 mg once per day, 4 weeks of receiving treatment followed by 2 weeks of no treatment). Patients with a ≥ 10% reduction in tumor burden (TB) after four cycles had sunitinib held, with restaging scans performed every two cycles. Sunitinib was reinitiated for two cycles in those patients with an increase in TB by ≥ 10%, and again held with ≥ 10% TB reduction. This intermittent sunitinib dosing continued until Response Evaluation Criteria in Solid Tumors-defined disease progression while receiving sunitinib, or unacceptable toxicity occurred. The primary objective was feasibility, defined as the proportion of eligible patients who underwent intermittent therapy. Results Of 37 patients enrolled, 20 were eligible for intermittent therapy and all patients (100%) entered the intermittent phase. Patients were not eligible for intermittent sunitinib because of progressive disease (n = 13), toxicity (n = 1), or consent withdrawal (n = 3) before the end of cycle 4. The objective response rate was 46% after the first four cycles of therapy. The median increase in TB during the periods off sunitinib was 1.6 cm (range, −2.9 to 3.4 cm) compared with the TB immediately before stopping sunitinib. Most patients exhibited a stable sawtooth pattern of TB reduction while receiving sunitinib and TB increase while not receiving sunitinib. Median progression-free survival to date is 22.4 months (95% CI, 5.4 to 37.6 months) and median overall survival is 34.8 months (95% CI, 14.8 months to not applicable). Conclusion Periodic extended sunitinib treatment breaks are feasible and clinical efficacy does not seem to be compromised.

scholarly journals Phase III Trial of Bevacizumab Plus Interferon Alfa Versus Interferon Alfa Monotherapy in Patients With Metastatic Renal Cell Carcinoma: Final Results of CALGB 90206

2010 ◽  
Vol 28 (13) ◽  
pp. 2137-2143 ◽  
Author(s):  
Brian I. Rini ◽  
Susan Halabi ◽  
Jonathan E. Rosenberg ◽  
Walter M. Stadler ◽  
Daniel A. Vaena ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Objective Response ◽  
Progression Free Survival ◽  
Interferon Alfa ◽  
Phase Iii ◽  
Phase Iii Trial ◽  
Grade 3

Purpose Bevacizumab is an antibody that binds vascular endothelial growth factor and has activity in metastatic renal cell carcinoma (RCC). Interferon alfa (IFN-α) is the historic standard initial treatment for RCC. A prospective, randomized, phase III trial of bevacizumab plus IFN-α versus IFN-α monotherapy was conducted. Patients and Methods Patients with previously untreated, metastatic clear cell RCC were randomly assigned to receive either bevacizumab (10 mg/kg intravenously every 2 weeks) plus IFN-α (9 million units subcutaneously three times weekly) or the same dose and schedule of IFN-α monotherapy in a multicenter phase III trial. The primary end point was overall survival (OS). Secondary end points were progression-free survival (PFS), objective response rate, and safety. Results Seven hundred thirty-two patients were enrolled. The median OS time was 18.3 months (95% CI, 16.5 to 22.5 months) for bevacizumab plus IFN-α and 17.4 months (95% CI, 14.4 to 20.0 months) for IFN-α monotherapy (unstratified log-rank P = .097). Adjusting on stratification factors, the hazard ratio was 0.86 (95% CI, 0.73 to 1.01; stratified log-rank P = .069) favoring bevacizumab plus IFN-α. There was significantly more grade 3 to 4 hypertension (HTN), anorexia, fatigue, and proteinuria for bevacizumab plus IFN-α. Patients who developed HTN on bevacizumab plus IFN-α had a significantly improved PFS and OS versus patients without HTN. Conclusion OS favored the bevacizumab plus IFN-α arm but did not meet the predefined criteria for significance. HTN may be a biomarker of outcome with bevacizumab plus IFN-α.

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