Current Treatment Outcomes in Japanese RCC Patients Treated With Avelumab Plus Axitinib as First-line Therapy: Retrospective Study (J-DART)

Study Overview
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Brief Summary
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This study is a multicenter, non-interventional, retrospective, medical chart review of patients with metastatic renal cell cancer(mRCC) treated with avelumab plus axitinib as a first-line therapy in Japan between 20 December 2019 and 20 December 2020. All decisions regarding clinical management and treatment of the participating patients were made by the investigator as part of standard care in real-world clinical setting and were not contingent upon the patient's participation in the study. Data will be collected if available per study site.

Official Title
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Retrospective, Multicenter, Observational Study to Evaluate Current Treatment Outcomes in Japanese Patients With Metastatic Renal Cell Carcinoma Treated With Avelumab Plus Axitinib as a First-line Therapy

Conditions
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Renal Cell Carcinoma

Intervention / Treatment
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* Drug: avelumab
* Drug: axitinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosed with metastatic renal cell cancer(mRCC) based on the General Rule for Clinical and Pathological Studies on Renal Cell Carcinoma (4th Edition) before receiving avelumab plus axitinib as a first-line therapy. Over 20 years of age at the time of metastatic renal cell cancer(mRCC) diagnosis. Start treatment with avelumab plus axitinib as a first-line therapy for metastatic renal cell cancer(mRCC) from 20 December 2019 to 20 December 2020. For patients who are still alive and have routine visits to the study site, evidence of a personally signed and dated informed consent document indicating that the patient has been informed of all pertinent aspects of the study. For patients who are still alive and had been transferred to another hospital, evidence that the patient has been informed of all pertinent aspects of the study and oral or written informed consent is obtained. Deceased patients are also included for inclusion criteria 1-3. Exclusion Criteria: There are no exclusion criteria for this study.

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Patients with metastatic renal cell carcinoma<br>Patients with metastatic renal cell carcinoma | Drug: avelumab<br>* as provided in real world practice<br>Drug: axitinib<br>* as provided in real world practice<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Categorized According to Eastern Cooperative Oncology Group Performance Status (ECOG-PS) | ECOG-PS assessed participant's performance status on a 5 point scale: 0= fully active/able to carry on all pre-disease activities without restriction; 1= restricted in physically strenuous activity, ambulatory/able to carry out light or sedentary work; 2= ambulatory (>50% of waking hours), capable of all self-care, unable to carry out any work activities; 3= capable of only limited self-care, confined to bed/chair >50% of waking hours; 4= completely disabled, cannot carry on any self-care, totally confined to bed/chair. Participants whose score was not known were reported against Unknown'. | Baseline (before first dose of avelumab plus axitinib, during data identification period from 20-Dec-2019 to 20-Dec-2020 [approximately 1 year]) retrieved data was analyzed during 4.5 months of this observational study | 
| Number of Participants Categorized According to International Metastatic RCC Database Consortium (IMDC) Risk Score | IMDC criteria had 6 risk factors: Karnofsky Performance Status less than (<) 80% (ability to perform ordinary tasks, 0 [dead] -100 [normal]); time from diagnosis to start of systemic therapy <1 year; corrected serum calcium; neutrophils and platelets more than (>) upper limit of normal (ULN); hemoglobin <lower limit of normal (LLN). Present risk factors were added, and then participants were stratified as: favorable (0 factor), intermediate (1-2 factors), poor (more than or equal to [>=]3 factors). | Baseline (before first dose of avelumab plus axitinib, during data identification period from 20-Dec-2019 to 20-Dec-2020 [approximately 1 year]) retrieved data was analyzed during 4.5 months of this observational study | 
| Number of Participants Categorized According to Fuhrman Grade | The four-tiered Fuhrman grading evaluates nuclear size, nuclear shape and presence of nucleolar prominence. Grade 1: small (=10 micrometer [mcm]) nuclear diameter, round/uniform nuclear shape and absent/inconspicuous nucleoli; Grade 2: large (=15 mcm) nuclear diameter, irregular outline nuclear shape and visible at *400 magnification nucleoli; Grade 3: larger (=20 mcm) nuclear diameter, obvious irregular outline nuclear shape and visible and prominent at *100 magnification nucleoli; Grade 4: grade 3 plus bizarre multilobed nuclei +/- spindle cells. Participants whose Fuhrman Grade were not known were reported against Unknown'. | Baseline (before first dose of avelumab plus axitinib, during data identification period from 20-Dec-2019 to 20-Dec-2020 [approximately 1 year]) retrieved data was analyzed during 4.5 months of this observational study | 
| Number of Participants Categorized According to Histological Type | In this outcome measure participants were reported according to the different histological type of mRCC including clear renal cell carcinoma, papillary renal cell carcinoma, chromophobe renal cell carcinoma and others. | Baseline (before first dose of avelumab plus axitinib, during data identification period from 20-Dec-2019 to 20-Dec-2020 [approximately 1 year]) retrieved data was analyzed during 4.5 months of this observational study | 
| Number of Participants Categorized According to Presence of Sarcomatoid Component | In this outcome measure, participants were categorized as Yes or No according to presence of sarcomatoid component were reported. | Baseline (before first dose of avelumab plus axitinib, during data identification period from 20-Dec-2019 to 20-Dec-2020 [approximately 1 year]) retrieved data was analyzed during 4.5 months of this observational study | 
| Number of Participants Categorized According to Tumor-node-metastases (TNM) Classification | TNM system is based on size of primary tumor (T), amount of spread to lymph nodes (N) and presence of metastases (M). T1: tumor <=20 millimeters (mm), T2: tumor >20 mm to <=50 mm, T3: >50 mm and TX: tumor cannot be assessed. N0: no lymph node metastases, N1: metastases to ipsilateral level I, II axillary lymph nodes, NX: Regional lymph nodes cannot be assessed. M0: no clinical/radiographic evidence of distant metastases, M1: distant detectable metastases as determined by clinical and radiographic means and/or histologically proven >0.2 mm, and MX: metastases cannot be assessed. | Baseline (before first dose of avelumab plus axitinib, during data identification period from 20-Dec-2019 to 20-Dec-2020 [approximately 1 year]) retrieved data was analyzed during 4.5 months of this observational study | 
| Number of Participants Categorized According to Number of Metastatic Organs | In this outcome measure participants were reported according to number of metastatic organs as a) 1 and, b) 2 or more. | Baseline (before first dose of avelumab plus axitinib, during data identification period from 20-Dec-2019 to 20-Dec-2020 [approximately 1 year]) retrieved data was analyzed during 4.5 months of this observational study | 
| Number of Participants Categorized According to Type of Site of Metastases | Sites of metastases included: metastases of lung, liver, bone, brain, regional lymph nodes, distant nodal metastases and others. One participant could have more than 1 type of metastases. | Baseline (before first dose of avelumab plus axitinib, during data identification period from 20-Dec-2019 to 20-Dec-2020 [approximately 1 year]) retrieved data was analyzed during 4.5 months of this observational study | 
| Number of Participants According to Presence of Complications | In this outcome measure participants were reported as Yes or No according to presence of complications. | Baseline (before first dose of avelumab plus axitinib, during data identification period from 20-Dec-2019 to 20-Dec-2020 [approximately 1 year]) retrieved data was analyzed during 4.5 months of this observational study | 
| Number of Participants Who Underwent Nephrectomy Previously | In this outcome measure, participants who underwent nephrectomy previously, were reported as Yes' or No. | Baseline (before first dose of avelumab plus axitinib, during data identification period from 20-Dec-2019 to 20-Dec-2020 [approximately 1 year]) retrieved data was analyzed during 4.5 months of this observational study | 
| Estimated Glomerular Filtration Rate (eGFR) | GFR is an index of kidney function that describes the flow of filtered fluid through the kidney. eGFR was reported in millimeter per minute per 1.73 square meter (ml/min/1.73 m^2). | Baseline (before first dose of avelumab plus axitinib, during data identification period from 20-Dec-2019 to 20-Dec-2020 [approximately 1 year]) retrieved data was analyzed during 4.5 months of this observational study | 
| Number of Participants With Proteinuria | Proteinuria is the presence of an excess of serum proteins in the urine, which may be an early sign of kidney disease. Here, negative = <15 milligrams per deciliter (mg/dL), positive=15-29 mg/dL, 1 = 30 mg/dL, 2= 100 mg/dL, 3= 300 mg/dL. | Baseline (before first dose of avelumab plus axitinib, during data identification period from 20-Dec-2019 to 20-Dec-2020 [approximately 1 year]) retrieved data was analyzed during 4.5 months of this observational study | 
| C-reactive Protein (CRP) | CRP was a laboratory measurement for evaluation of an acute phase reactant of inflammation through the use of an ultra-sensitive assay. | Baseline (before first dose of avelumab plus axitinib, during data identification period from 20-Dec-2019 to 20-Dec-2020 [approximately 1 year]) retrieved data was analyzed during 4.5 months of this observational study | 
| Number of Participants Categorized According to Smoking Status | In this outcome measure, participants with smoking history were reported as No (No smoking history, never smoked), No (Smoking history exists, quit smoking), Yes (currently smoking). Participant whose smoking status was not known were reported against Unknown. | Baseline (before first dose of avelumab plus axitinib, during data identification period from 20-Dec-2019 to 20-Dec-2020 [approximately 1 year]) retrieved data was analyzed during 4.5 months of this observational study | 
| Number of Participants Who Took Concomitant Drugs | In this outcome measure, participants who took concomitant drugs were reported. | Baseline (before first dose of avelumab plus axitinib, during data identification period from 20-Dec-2019 to 20-Dec-2020 [approximately 1 year]) retrieved data was analyzed during 4.5 months of this observational study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Treatment Failure (TTF) of Avelumab Plus Axitinib as a First-line Therapy | TTF was defined as the time from the date of first dose of avelumab plus axitinib as first line therapy to the end of treatment for any cause earlier, including death. Kaplan-Meier method was used for analysis. | From index date up to 20-June-2021, where index date was date of first prescription for avelumab plus axitinib between 20-Dec-2019 and 20 December 2020 (maximum observation period was of 1.5 years approximately). | 
| Real-world Progression Free Survival (PFS) | PFS was defined as time from start of avelumab/axitinib treatment to date of first disease progression (DP) (as clinically assessed by local investigator based on radiology, laboratory evidence, pathology, or other assessments) or death due to any cause, whichever came first. If there were no clinical records of death or disease progression, they were censored at the date of initiation of the next line of therapy for the participants undertaking 2 or more lines of therapy based on the record, or at their last visit date during the study period for the participants undertaking only 1 line of therapy based on the record. | From avelumab plus axitinib initiation to disease progression or death due to any cause/censored date (during data identification period from 20-Dec-2019 to 20-Jun-2021 [approx 1.6 years]); retrieved data was analyzed during 4.5 months of this OS | 
| Percentage of Participants With Objective Response | Objective response was defined as percentage of participants with complete response (CR) or partial response (PR) as the best adjudication result in a method complied with RECIST version. 1.1 tumor assessment as closely as possible in clinical practice by investigator's judgment. CR: disappearance of all non-nodal target lesions and of all non-target lesions. In addition, any pathological lymph nodes assigned as target lesions/ non-target lesions must have a reduction in short axis to <10 mm. PR: at least a 30 percent (%) decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. | From avelumab plus axitinib initiation to CR or PR (during data identification period from 20-Dec-2019 to 20-Jun-2021 [approximately 1.6 years]) retrieved data was analyzed during 4.5 months of this observational study | 
| Time to Treatment Failure in Participants With Avelumab and Axitinib Treatment | TTF was defined as the time from the date of first dose of avelumab plus axitinib to the end of treatment for any cause earlier, including death. Kaplan-Meier method was used for analysis. | From avelumab plus axitinib initiation to end of treatment (during data identification period from 20-Dec-2019 to 20-Jun-2021 [approximately 1.6 years]) retrieved data was analyzed during 4.5 months of this observational study | 
| Number of Participants With Discontinuation and Interruption of Avelumab and Axitinib Treatment | In this outcome measure, number of participants who discontinued and had interruption of avelumab and axitinib treatment were reported. | From avelumab plus axitinib initiation to end of treatment (during data identification period from 20-Dec-2019 to 20-Jun-2021 [approximately 1.6 years]); retrieved data was analyzed during 4.5 months of this observational study | 
| Number of Participants With Reason for Discontinuation of Avelumab Treatment | In this outcome measure, participant who discontinued the avelumab treatment due to reasons including disease progression, adverse event, sufficient efficacy and others were reported. One participant could have more than 1 reason for discontinuation of treatment. | From avelumab plus axitinib initiation to end of treatment (during data identification period from 20-Dec-2019 to 20-Jun-2021 [approximately 1.5 years]); retrieved data was analyzed during 4.5 months of this observational study | 
| Number of Participants With Reason for Discontinuation of Axitinib Treatment | In this outcome measure, participant who discontinued the axitinib treatment due to reasons including disease progression, adverse event, sufficient efficacy and others were reported. One participant could have more than 1 reason for discontinuation of treatment. | From avelumab plus axitinib initiation to end of treatment (during data identification period from 20-Dec-2019 to 20-Jun-2021 [approximately 1.5 years]); retrieved data was analyzed during 4.5 months of this observational study | 
| Number of Participants With Reason for Interruption of Avelumab Treatment | In this outcome measure, participant who had treatment interruption due to reasons including adverse event, sufficient efficacy and others were reported. One participant could have more than 1 reason for interruption of treatment. | From avelumab plus axitinib initiation to end of treatment (during data identification period from 20-Dec-2019 to 20-Jun-2021 [approximately 1.5 years]); retrieved data was analyzed during 4.5 months of this observational study | 
| Number of Participants With Reason for Interruption of Axitinib Treatment | In this outcome measure, participant who had treatment interruption due to reasons including adverse event, sufficient efficacy and others were reported. One participant could have more than 1 reason for interruption of treatment. | From avelumab plus axitinib initiation to end of treatment (during data identification period from 20-Dec-2019 to 20-Jun-2021 [approximately 1.5 years]); retrieved data was analyzed during 4.5 months of this observational study | 
| Number of Participants With Dose Modification of Axitinib Treatment | In this outcome measure, participants who had dose modification (increase/decrease) were reported. | From avelumab plus axitinib initiation to end of treatment (during data identification period from 20-Dec-2019 to 20-Jun-2021 [approximately 1.5 years]); retrieved data was analyzed during 4.5 months of this observational study | 
| Number of Participants According to Reason for Dose Modification of Axitinib Treatment | In this outcome measure, number of participants were reported against the reasons for dose modification of axitinib treatment. One participant could have more than 1 reason for modification of axitinib treatment. | From avelumab plus axitinib initiation to end of treatment (during data identification period from 20-Dec-2019 to 20-Jun-2021 [approximately 1.5 years]); retrieved data was analyzed during 4.5 months of this observational study | 
| Cumulative Dose of Corticosteroid for Immune-related Adverse Events (irAE) During Avelumab Plus Axitinib Treatment | Immune-related adverse events (irAEs) was defined as the serious side effect of immune checkpoint inhibitor therapy for participants with advanced cancer. | From avelumab plus axitinib initiation to end of treatment (during data identification period from 20-Dec-2019 to 20-Jun-2021 [approximately 1.5 years]); retrieved data was analyzed during 4.5 months of this observational study | 
| Duration of Corticosteroid Treatment for irAE During Avelumab Plus Axitinib Treatment |  | From avelumab plus axitinib initiation to end of treatment (during data identification period from 20-Dec-2019 to 20-Jun-2021 [approximately 1.5 years]); retrieved data was analyzed during 4.5 months of this observational study | 
| Number of Corticosteroid Doses for irAE During Avelumab Plus Axitinib Treatment |  | From avelumab plus axitinib initiation to end of treatment (during data identification period from 20-Dec-2019 to 20-Jun-2021 [approximately 1.5 years]); retrieved data was analyzed during 4.5 months of this observational study | 
| Number of Participants With Presence of Pre-medication for Potential Infusion-related Reaction of Avelumab | In this outcome measure, number of participants who were on pre-medication and presence of these medications were reason for potential infusion-related reaction of avelumab, were reported. | From avelumab plus axitinib initiation to end of treatment (during data identification period from 20-Dec-2019 to 20-Jun-2021 [approximately 1.5 years]); retrieved data was analyzed during 4.5 months of this observational study | 
| Number of Participants Categorized According to Type of Pre-medication for Infusion-related Reaction of Avelumab | In this outcome measure, number of participants who were on pre-medication and presence of these medications were reason for potential infusion-related reaction of avelumab, were reported according to type of pre-medications. One participant could have taken more than 1 type of pre-medication. | From avelumab plus axitinib initiation to end of treatment (during data identification period from 20-Dec-2019 to 20-Jun-2021 [approximately 1.5 years]); retrieved data was analyzed during 4.5 months of this observational study | 
| Number of Participants Who Received Treatment for Infusion-related Reaction of Avelumab | In this outcome measure, number of participants who received any treatment for infusion-related reaction of avelumab were reported. | From avelumab plus axitinib initiation to end of treatment (during data identification period from 20-Dec-2019 to 20-Jun-2021 [approximately 1.5 years]); retrieved data was analyzed during 4.5 months of this observational study | 
| Number of Participants by Type of Received Subsequent Treatment After Avelumab Plus Axitinib | In this outcome measure, number of participants who received subsequent treatment after avelumab plus axitinib therapy, were reported according to type of subsequent treatment including tyrosine kinase inhibitors (TKI), immuno-oncology (IO) drugs and others. Categories with at least 1 non-zero data are reported below. | From avelumab plus axitinib end of treatment to end of study observation (during data identification period from 20-Dec-2019 to 20-Jun-2021 [approximately 1.5 years]); retrieved data was analyzed during 4.5 months of this observational study | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Retrospective, Multicenter, Non-interventional, Medical chart review, Japan, Metastatic renal cell cancer(mRCC), Avelumab, Axitinib, First-line therapy, Standard care in real-world clinical setting