Metastatic Renal Cell Carcinoma
Conditions
Keywords
sutent rechallenge
Brief summary
Retrospective and prospective study in mRCC patients treated with sutent in first line and rechallenged by Sutent in 3rd and 4th line.
Detailed description
A sample size of n = 40 patients will allow to estimate of the median PFS with a precision around 1.8 months (based on data from Rini et al.) This retrospective and prospective study is designed to estimate the effect of Sutent rechallenge. The PFS (estimated from Kaplan-Meier estimate) will be the primary endpoints. In addition, the effects of sunitinib at the 2 periods of treatment (i.e. first line sunitinib vs. rechallenge) will be compared by Wilcoxon signed-rank test for PFS values and by McNemar test for overall response rate (ORR).
Interventions
OTHERsunitinib: observational study
Observational study evaluating patients who were treated with sunitinib in 1st line and in 3rd line
Sponsors
Pfizer
Study design
Observational model
COHORT
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically documented metastatic RCC containing predominantly clear cell component. * Previously received sunitinib in first line, 2 or more antitumor therapies subsequently and then received sunitinib for a second time. * At least 1 cycle of sunitinib rechallenge (1 cycle= 4 weeks on/2 weeks off). * At least 1 measurable lesion that can be accurately measured in at least 1 dimension with the longest diameter (LD) ³ 10 mm when measured by spiral computerized tomography (CT) (5-mm slice thickness contiguous) or ³ 20 mm when measured by conventional CT (10-mm slice thickness contiguous). The lesion must be ³ 2 times the size of the slice thickness per RECIST criteria. * Life expectancy of at least 3 months.
Exclusion criteria
* Patient who didn't receive Sunitinib in first line. * Patient who received less than one line of treatment .
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival: Second Line of Treatment | From start of treatment up to 22.9 months | The PFS was defined as the time interval between the start date of treatment and the date of progression as assessed by the investigator or date of death occurring after treatment initiation, whichever occurred first. Duration of progression free survival= \[(Date of mRCC progression - Start date of the treatment) + 1)\]/ 365.25 x 12. Progression was defined as an increase in visible disease. Second-line treatment were divided in two groups: Group A (received treatment with: bevacizumab (with interferon), bevacizumab (without interferon), sorafenib, axitinib) and Group B (received treatment with: temsirolimus, everolimus). |
| Progression Free Survival With Sunitinib as First Line of Therapy | From start of treatment up to 66.6 months | The PFS was defined as the time interval between the start date of treatment and the date of progression as assessed by the investigator or date of death occurring after treatment initiation, whichever occurred first. Duration of progression free survival= \[(Date of mRCC progression - Start date of the treatment) + 1)\]/ 365.25 x 12. Progression was defined as an increase in visible disease. |
| Progression Free Survival for Re-challenge With Sunitinib | From start of treatment up to 52.2 months | The PFS was defined as the time interval between the start date of treatment and the date of progression as assessed by the investigator or date of death occurring after treatment initiation, whichever occurred first. Duration of progression free survival= \[(Date of mRCC progression - Start date of the treatment) + 1)\]/ 365.25 x 12. Progression was defined as an increase in visible disease. |
| Progression Free Survival: Third Line Treatment | From start of treatment up to 23.7 months | The PFS was defined as the time interval between the start date of treatment and the date of progression as assessed by the investigator or date of death occurring after treatment initiation, whichever occurred first. Duration of progression free survival= \[(Date of mRCC progression - Start date of the treatment) + 1)\]/ 365.25 x 12. Progression was defined as an increase in visible disease. Third-line treatment were divided in two groups: Group A (received treatment with: bevacizumab (with interferon), bevacizumab (without interferon), sorafenib, axitinib) and Group B (received treatment with: temsirolimus, everolimus). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | Baseline up to death or end of study (up to 98.0 months) | Overall survival of patients under treatment was evaluated by calculating the time between date of initiation of treatment (1st line) and date of death, if the latter occurred before the end of the study. Duration of Overall Survival =(Date of death - Start date of treatment) + 1)/365.25 x 12. |
| Percentage of Participants With Objective Response | Baseline up to 98.0 months | Percentage of participants with objective response based assessment of complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). CR was defined as complete disappearance of all target lesions and non-target lesions, with the exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis \<10 mm). No new lesions. PR was defined as \>=30% decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease. No new lesions. Percentage of participants with objective response was calculated for the 1st-line of therapy with Sunitinib, Sunitinib re-challenge and for retreatment with Sunitinib as 3rd-line of therapy or more. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of Participant With Adverse Events (AEs) or Serious Adverse Events (SAEs) | Baseline up to 24 months | An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. AEs include both serious as well as non-serious AEs. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. |
Countries
France
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Metastatic Renal Cell Carcinoma (mRCC) Cohort Participants diagnosed with mRCC who met the selection criteria and received first-line sunitinib as per standard local practice, followed by one or more lines of different treatments (bevacizumab with interferon, bevacizumab without interferon, sorafenib, axitinib, temsirolimus or everolimus), and, lastly were rechallenged with sunitinib between 2006 and May 2013 were included in this non-interventional study. | 52 |
| Total | 52 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Case report form not completed | 4 |
| Overall Study | Death | 10 |
| Overall Study | Did not complete re-challenge | 1 |
| Overall Study | Discontinued prior initiation: sunitinib | 1 |
| Overall Study | Disease progression | 36 |
| Overall Study | Intolerance to treatment | 4 |
| Overall Study | Invalidated centre | 3 |
Baseline characteristics
| Characteristic | Metastatic Renal Cell Carcinoma (mRCC) Cohort |
|---|---|
| Age, Continuous | 60.1 years STANDARD_DEVIATION 9.8 |
| Sex: Female, Male Female | 13 Participants |
| Sex: Female, Male Male | 39 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 13 / 52 |
| serious Total, serious adverse events | 21 / 52 |
Outcome results
Primary
Progression Free Survival for Re-challenge With Sunitinib
The PFS was defined as the time interval between the start date of treatment and the date of progression as assessed by the investigator or date of death occurring after treatment initiation, whichever occurred first. Duration of progression free survival= \[(Date of mRCC progression - Start date of the treatment) + 1)\]/ 365.25 x 12. Progression was defined as an increase in visible disease.
Time frame: From start of treatment up to 52.2 months
Population: Evaluable population: All participants included in the analysis. Here N signifies number of participants who were analyzed for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Metastatic Renal Cell Carcinoma (mRCC) Cohort | Progression Free Survival for Re-challenge With Sunitinib | 7.9 months |
Primary
Progression Free Survival: Second Line of Treatment
The PFS was defined as the time interval between the start date of treatment and the date of progression as assessed by the investigator or date of death occurring after treatment initiation, whichever occurred first. Duration of progression free survival= \[(Date of mRCC progression - Start date of the treatment) + 1)\]/ 365.25 x 12. Progression was defined as an increase in visible disease. Second-line treatment were divided in two groups: Group A (received treatment with: bevacizumab (with interferon), bevacizumab (without interferon), sorafenib, axitinib) and Group B (received treatment with: temsirolimus, everolimus).
Time frame: From start of treatment up to 22.9 months
Population: Evaluable population: All participants included in the analysis. Here N signifies number of participants who were analyzed for this outcome measure and n signifies those participants who were evaluable for respective treatment group.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Metastatic Renal Cell Carcinoma (mRCC) Cohort | Progression Free Survival: Second Line of Treatment | Group A (n=21) | 5.0 months |
| Metastatic Renal Cell Carcinoma (mRCC) Cohort | Progression Free Survival: Second Line of Treatment | Group B (n=29) | 6.2 months |
Primary
Progression Free Survival: Third Line Treatment
The PFS was defined as the time interval between the start date of treatment and the date of progression as assessed by the investigator or date of death occurring after treatment initiation, whichever occurred first. Duration of progression free survival= \[(Date of mRCC progression - Start date of the treatment) + 1)\]/ 365.25 x 12. Progression was defined as an increase in visible disease. Third-line treatment were divided in two groups: Group A (received treatment with: bevacizumab (with interferon), bevacizumab (without interferon), sorafenib, axitinib) and Group B (received treatment with: temsirolimus, everolimus).
Time frame: From start of treatment up to 23.7 months
Population: Evaluable population: All participants included in the analysis. Here N signifies number of participants who were analyzed for this outcome measure and n signifies those participants who were evaluable for respective treatment group.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Metastatic Renal Cell Carcinoma (mRCC) Cohort | Progression Free Survival: Third Line Treatment | Group A (n=20) | 4.8 months |
| Metastatic Renal Cell Carcinoma (mRCC) Cohort | Progression Free Survival: Third Line Treatment | Group B (n=19) | 10.8 months |
Primary
Progression Free Survival With Sunitinib as First Line of Therapy
The PFS was defined as the time interval between the start date of treatment and the date of progression as assessed by the investigator or date of death occurring after treatment initiation, whichever occurred first. Duration of progression free survival= \[(Date of mRCC progression - Start date of the treatment) + 1)\]/ 365.25 x 12. Progression was defined as an increase in visible disease.
Time frame: From start of treatment up to 66.6 months
Population: Evaluable population: All participants included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Metastatic Renal Cell Carcinoma (mRCC) Cohort | Progression Free Survival With Sunitinib as First Line of Therapy | 18.4 months |
Secondary
Overall Survival
Overall survival of patients under treatment was evaluated by calculating the time between date of initiation of treatment (1st line) and date of death, if the latter occurred before the end of the study. Duration of Overall Survival =(Date of death - Start date of treatment) + 1)/365.25 x 12.
Time frame: Baseline up to death or end of study (up to 98.0 months)
Population: Evaluable population: All participants included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Metastatic Renal Cell Carcinoma (mRCC) Cohort | Overall Survival | 55.9 months |
Secondary
Percentage of Participants With Objective Response
Percentage of participants with objective response based assessment of complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). CR was defined as complete disappearance of all target lesions and non-target lesions, with the exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis \<10 mm). No new lesions. PR was defined as \>=30% decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease. No new lesions. Percentage of participants with objective response was calculated for the 1st-line of therapy with Sunitinib, Sunitinib re-challenge and for retreatment with Sunitinib as 3rd-line of therapy or more.
Time frame: Baseline up to 98.0 months
Population: Evaluable population: All participants included in the analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Metastatic Renal Cell Carcinoma (mRCC) Cohort | Percentage of Participants With Objective Response | First line treatment | 53.8 percentage of participants |
| Metastatic Renal Cell Carcinoma (mRCC) Cohort | Percentage of Participants With Objective Response | Third line treatment | 15.4 percentage of participants |
| Metastatic Renal Cell Carcinoma (mRCC) Cohort | Percentage of Participants With Objective Response | Sunitinib re-challenge | 75.0 percentage of participants |
Other Pre-specified
Number of Participant With Adverse Events (AEs) or Serious Adverse Events (SAEs)
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. AEs include both serious as well as non-serious AEs. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
Time frame: Baseline up to 24 months
Population: Evaluable population: All participants included in the analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Metastatic Renal Cell Carcinoma (mRCC) Cohort | Number of Participant With Adverse Events (AEs) or Serious Adverse Events (SAEs) | AEs | 24 participants |
| Metastatic Renal Cell Carcinoma (mRCC) Cohort | Number of Participant With Adverse Events (AEs) or Serious Adverse Events (SAEs) | SAEs | 21 participants |