Renal Cell Carcinoma
Conditions
Keywords
Advanced Renal Cell Carcinoma (aRCC)
Brief summary
To assess how dose reductions or treatment interruptions related to axitinib can be implemented to manage and resolve adverse events occurring among patients with advanced renal cell carcinoma treated with first-line axitinib in combination with avelumab or pembrolizumab
Detailed description
The specific objectives of the study are as follows: Describe incident adverse events (AEs) experienced among patients with advanced RCC who received first-line axitinib in combination with immuno-oncology (IO) therapies. * Type and seriousness of AEs (ie, diarrhea, fatigue, hypertension, nausea, palmar plantar erythrodysesthesia \[hand-foot syndrome\]). * Proportion of patients who experienced repeated AEs. * Time from treatment initiation to AE onset, overall and by type and seriousness of AEs. Among patients with advanced RCC who developed incident AEs while receiving first line axitinib in combination with IO therapies, characterize and describe management strategies for AEs, stratified by type and seriousness of AEs. * Proportion of patients who used each of the following management strategies: * No action for axitinib and IO therapy; * No action for axitinib, but treatment modification for IO therapy (ie, treatment interruption, treatment discontinuation); * Axitinib dose reduction, but no action for IO therapy; * Axitinib treatment interruption, but no action for IO therapy; * Axitinib treatment discontinuation, but no action for IO therapy; * Axitinib dose reduction, and treatment modification for IO therapy; * Axitinib treatment interruption, and treatment modification for IO therapy; * Axitinib treatment discontinuation, and treatment modification for IO therapy. * Average axitinib dose reduction (absolute and percentage change), where applicable. * Duration of treatment interruption, where applicable. Assess the frequency of and time to AE resolution (from AE onset and initiation of management strategy, separately) among patients with advanced RCC who developed incident AEs while receiving first-line axitinib in combination with IO therapies according to different management strategies implemented, stratified further by type and seriousness of AEs, as allowed by sample size. The above objectives will also be conducted for repeated AEs of the same type
Interventions
DRUGAxitinib
Inlyta, axitinib
DRUGAvelumab
Avelumab, Bavencio
DRUGPembrolizumab
Pembrolizumab, Keytruda
Sponsors
Pfizer
Study design
Observational model
OTHER
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Physicians meeting the following criteria will be invited to participate in the chart review study: * Specialty in oncology * Access to complete medical records for at least one patient with advanced RCC who meets the patient eligibility criteria Eligible oncologists will be asked to select up to three patients meeting the following criteria for inclusion in the chart review study: * Confirmed diagnosis with advanced RCC * Treated with first-line axitinib/IO combination therapy at or after diagnosis * Experienced at least one AE (i.e., diarrhea, fatigue, nausea, hypertension, and palmar-plantar erythrodysesthesia \[hand-foot syndrome\]) while treated with axitinib/IO combination therapy * Age 18 years or older at the time of advanced RCC diagnosis * Initiated axitinib/IO combination therapy at least 3 months prior to the start date of medical chart abstraction to ensure sufficient follow-up time
Exclusion criteria
There are no
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Different Type of Adverse Events | Observation period of maximum up to 7.1 months; duration of this retrospective study was approximately 1.5 months | An AE was any untoward medical occurrence in a participant who received study medication without regard to possibility of causal relationship to it.Index date was defined as the initiation of first-line axitinib (used in combination with IO therapy) on or after May 2019, which marked FDA approval of axitinib in combination with avelumab for first-line advanced RCC treatment. Observation period was time from index date to the earliest of initiation of a second line therapy, death, loss to follow-up, or date of chart abstraction. Data, index date, and observation period were on the basis of data extracted from medical charts of participants. |
| Number of Participants With Serious Adverse Events | 6 months | AE was considered serious when it: resulted in death, life-threatening, requires in-participant hospitalization or prolongation of existing hospitalization, resulted in a persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or was an important medical event that may jeopardize the participant or may require intervention to prevent one of the outcomes listed above. Index date was defined as the initiation of first-line axitinib (used in combination with IO therapy) on or after May 2019, which marked FDA approval of axitinib in combination with avelumab for first-line advanced RCC treatment. Observation period was time from index date to the earliest of initiation of a second line therapy, death, loss to follow-up, or date of chart abstraction. Data, index date, and observation period were on the basis of data extracted from medical charts of participants. |
| Duration From Treatment Initiation to Onset of Adverse Events | Observation period of maximum up to 7.1 months; duration of this retrospective study was approximately 1.5 months | An AE was any untoward medical occurrence in a participant who received study medication without regard to possibility of causal relationship to it. In this outcome measure time from index date to occurrence of incidence of any AE is reported. Index date was defined as the initiation of first-line axitinib (used in combination with IO therapy) on or after May 2019, which marked FDA approval of axitinib in combination with avelumab for first-line advanced RCC treatment. Observation period was time from index date to the earliest of initiation of a second line therapy, death, loss to follow-up, or date of chart abstraction. Data, index date, and observation period were on the basis of data extracted from medical charts of participants. |
| Duration of Adverse Events From Onset to Resolution | Observation period of maximum up to 7.1 months; duration of this retrospective study was approximately 1.5 months | The time to resolution from AE onset and from initiation of management strategy was calculated for all AEs experienced including repeated AEs. The time to resolution of AE (from the onset of AE and from the initiation of management strategies) was separately estimated using Kaplan-Meier analysis; median time to event will be reported. Index date was defined as the initiation of first-line axitinib (used in combination with IO therapy) on or after May 2019, which marked FDA approval of axitinib in combination with avelumab for first-line advanced RCC treatment. Observation period was time from index date to the earliest of initiation of a second line therapy, death, loss to follow-up, or date of chart abstraction. Data, index date, and observation period were on the basis of data extracted from medical charts of participants. |
| Number of Adverse Events Classified According to Type of Management Strategy | Observation period of maximum up to 7.1 months; duration of this retrospective study was approximately 1.5 months | An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship with the study treatment. Index date was defined as the initiation of first-line axitinib (used in combination with IO therapy) on or after May 2019, which marked FDA approval of axitinib in combination with avelumab for first-line advanced RCC treatment. Observation period was time from index date to the earliest of initiation of a second line therapy, death, loss to follow-up, or date of chart abstraction. Data, index date, and observation period were on the basis of data extracted from medical charts of participants. |
| Duration of Treatment Interruption for Axitinib | Observation period of maximum up to 7.1 months; duration of this retrospective study was approximately 1.5 month | Duration of treatment interruption was calculated as the total days of treatment interruption. Index date was defined as the initiation of first-line axitinib (used in combination with IO therapy) on or after May 2019, which marked FDA approval of axitinib in combination with avelumab for first-line advanced RCC treatment. Observation period was time from index date to the earliest of initiation of a second line therapy, death, loss to follow-up, or date of chart abstraction. Data, index date, and observation period were on the basis of data extracted from medical charts of participants. |
| Maximum Axitinib Dose Reduction | Observation period of maximum up to 7.1 months; duration of this retrospective study was approximately 1.5 months | Maximum axitinib dose reduction was calculated as the difference between axitinib dose at AE onset and the minimum axitinib dose recorded between the date of AE onset and either the date of AE resolution (if the AE had a reported resolution date) or the end of follow up (if the AE did not have a reported resolution date).Index date was defined as the initiation of first-line axitinib (used in combination with IO therapy) on or after May 2019, which marked FDA approval of axitinib in combination with avelumab for first-line advanced RCC treatment. Observation period was time from index date to the earliest of initiation of a second line therapy, death, loss to follow-up, or date of chart abstraction. Data, index date, and observation period were on the basis of data extracted from medical charts of participants. |
Countries
United States
Participant flow
Recruitment details
Data of participants with advanced Renal cell carcinoma (RCC) who received first line therapy of Axitinib in combination with Immuno-oncology (IO) therapy was observed in this study. Oncologists abstracted data from medical charts of eligible participants using an online electronic case report form (eCRF). Abstracted data was evaluated over 1.5 months of this retrospective study.
Participants by arm
| Arm | Count |
|---|---|
| Axitinib + IOs Participants with advanced RCC who received first-line axitinib in combination with IO (avelumab or pembrolizumab) in real world per routine clinical practice, their data were abstracted from medical charts and observed during this retrospective study. | 481 |
| Total | 481 |
Baseline characteristics
| Characteristic | Axitinib + IOs |
|---|---|
| Age, Continuous | 61.9 Years STANDARD_DEVIATION 9.5 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 5 Participants |
| Race/Ethnicity, Customized Asian | 15 Participants |
| Race/Ethnicity, Customized Black or African American | 76 Participants |
| Race/Ethnicity, Customized Missing | 20 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 1 Participants |
| Race/Ethnicity, Customized Unknown or Not Reported | 6 Participants |
| Race/Ethnicity, Customized White | 358 Participants |
| Sex: Female, Male Female | 161 Participants |
| Sex: Female, Male Male | 320 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 32 / 481 |
| other Total, other adverse events | 265 / 481 |
| serious Total, serious adverse events | 130 / 481 |
Outcome results
Primary
Duration From Treatment Initiation to Onset of Adverse Events
An AE was any untoward medical occurrence in a participant who received study medication without regard to possibility of causal relationship to it. In this outcome measure time from index date to occurrence of incidence of any AE is reported. Index date was defined as the initiation of first-line axitinib (used in combination with IO therapy) on or after May 2019, which marked FDA approval of axitinib in combination with avelumab for first-line advanced RCC treatment. Observation period was time from index date to the earliest of initiation of a second line therapy, death, loss to follow-up, or date of chart abstraction. Data, index date, and observation period were on the basis of data extracted from medical charts of participants.
Time frame: Observation period of maximum up to 7.1 months; duration of this retrospective study was approximately 1.5 months
Population: All eligible participants whose data were extracted from medical records and observed in the study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Axitinib + IOs | Duration From Treatment Initiation to Onset of Adverse Events | 1.0 Months |
Primary
Duration of Adverse Events From Onset to Resolution
The time to resolution from AE onset and from initiation of management strategy was calculated for all AEs experienced including repeated AEs. The time to resolution of AE (from the onset of AE and from the initiation of management strategies) was separately estimated using Kaplan-Meier analysis; median time to event will be reported. Index date was defined as the initiation of first-line axitinib (used in combination with IO therapy) on or after May 2019, which marked FDA approval of axitinib in combination with avelumab for first-line advanced RCC treatment. Observation period was time from index date to the earliest of initiation of a second line therapy, death, loss to follow-up, or date of chart abstraction. Data, index date, and observation period were on the basis of data extracted from medical charts of participants.
Time frame: Observation period of maximum up to 7.1 months; duration of this retrospective study was approximately 1.5 months
Population: All eligible participants whose data were extracted from medical records and observed in the study.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Axitinib + IOs | Duration of Adverse Events From Onset to Resolution | Overall | 21.0 Days |
| Axitinib + IOs | Duration of Adverse Events From Onset to Resolution | Severe AE's | 17.0 Days |
Primary
Duration of Treatment Interruption for Axitinib
Duration of treatment interruption was calculated as the total days of treatment interruption. Index date was defined as the initiation of first-line axitinib (used in combination with IO therapy) on or after May 2019, which marked FDA approval of axitinib in combination with avelumab for first-line advanced RCC treatment. Observation period was time from index date to the earliest of initiation of a second line therapy, death, loss to follow-up, or date of chart abstraction. Data, index date, and observation period were on the basis of data extracted from medical charts of participants.
Time frame: Observation period of maximum up to 7.1 months; duration of this retrospective study was approximately 1.5 month
Population: All eligible participants whose data were extracted from medical records and observed in the study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Axitinib + IOs | Duration of Treatment Interruption for Axitinib | 13.0 Days |
Primary
Maximum Axitinib Dose Reduction
Maximum axitinib dose reduction was calculated as the difference between axitinib dose at AE onset and the minimum axitinib dose recorded between the date of AE onset and either the date of AE resolution (if the AE had a reported resolution date) or the end of follow up (if the AE did not have a reported resolution date).Index date was defined as the initiation of first-line axitinib (used in combination with IO therapy) on or after May 2019, which marked FDA approval of axitinib in combination with avelumab for first-line advanced RCC treatment. Observation period was time from index date to the earliest of initiation of a second line therapy, death, loss to follow-up, or date of chart abstraction. Data, index date, and observation period were on the basis of data extracted from medical charts of participants.
Time frame: Observation period of maximum up to 7.1 months; duration of this retrospective study was approximately 1.5 months
Population: All eligible participants whose data were extracted from medical records and observed in the study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Axitinib + IOs | Maximum Axitinib Dose Reduction | 3.0 Milligrams twice daily |
Primary
Number of Adverse Events Classified According to Type of Management Strategy
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship with the study treatment. Index date was defined as the initiation of first-line axitinib (used in combination with IO therapy) on or after May 2019, which marked FDA approval of axitinib in combination with avelumab for first-line advanced RCC treatment. Observation period was time from index date to the earliest of initiation of a second line therapy, death, loss to follow-up, or date of chart abstraction. Data, index date, and observation period were on the basis of data extracted from medical charts of participants.
Time frame: Observation period of maximum up to 7.1 months; duration of this retrospective study was approximately 1.5 months
Population: All eligible participants whose data were extracted from medical records and observed in the study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Axitinib + IOs | Number of Adverse Events Classified According to Type of Management Strategy | No Action | 198 Adverse Events |
| Axitinib + IOs | Number of Adverse Events Classified According to Type of Management Strategy | Axitinib modifications (with or without supportive care) | 251 Adverse Events |
| Axitinib + IOs | Number of Adverse Events Classified According to Type of Management Strategy | Axitinib modifications with IO treatment modification | 96 Adverse Events |
Primary
Number of Participants With Different Type of Adverse Events
An AE was any untoward medical occurrence in a participant who received study medication without regard to possibility of causal relationship to it.Index date was defined as the initiation of first-line axitinib (used in combination with IO therapy) on or after May 2019, which marked FDA approval of axitinib in combination with avelumab for first-line advanced RCC treatment. Observation period was time from index date to the earliest of initiation of a second line therapy, death, loss to follow-up, or date of chart abstraction. Data, index date, and observation period were on the basis of data extracted from medical charts of participants.
Time frame: Observation period of maximum up to 7.1 months; duration of this retrospective study was approximately 1.5 months
Population: All eligible participants whose data were extracted from medical records and observed in the study.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Axitinib + IOs | Number of Participants With Different Type of Adverse Events | Fatigue | 232 Participants |
| Axitinib + IOs | Number of Participants With Different Type of Adverse Events | Diarrhea | 184 Participants |
| Axitinib + IOs | Number of Participants With Different Type of Adverse Events | Nausea | 141 Participants |
| Axitinib + IOs | Number of Participants With Different Type of Adverse Events | Hypertension | 106 Participants |
| Axitinib + IOs | Number of Participants With Different Type of Adverse Events | Palmar-plantar erythrodysesthesia | 54 Participants |
Primary
Number of Participants With Serious Adverse Events
AE was considered serious when it: resulted in death, life-threatening, requires in-participant hospitalization or prolongation of existing hospitalization, resulted in a persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or was an important medical event that may jeopardize the participant or may require intervention to prevent one of the outcomes listed above. Index date was defined as the initiation of first-line axitinib (used in combination with IO therapy) on or after May 2019, which marked FDA approval of axitinib in combination with avelumab for first-line advanced RCC treatment. Observation period was time from index date to the earliest of initiation of a second line therapy, death, loss to follow-up, or date of chart abstraction. Data, index date, and observation period were on the basis of data extracted from medical charts of participants.
Time frame: 6 months
Population: All eligible participants whose data were extracted from medical records and observed in the study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Axitinib + IOs | Number of Participants With Serious Adverse Events | 130 Participants |