Treatment Outcomes in Japanese RCC Patients Treated With Avelumab Plus Axitinib as First-line Therapy: Retrospective Study (J-DART2)

A Multicenter, NI, Retrospective, Observational Study Evaluating Real-World Treatment Outcomes in Japanese Patients With Metastatic Renal Cell Carcinoma (mRCC) Treated With Avelumab Plus Axitinib as First-line Therapy: J-DART2

This study is a multicenter, non-interventional, retrospective, medical chart review of participants with metastatic renal cell cancer(mRCC) treated with avelumab plus axitinib as a first-line therapy in Japan between 20 December 2019 and 17 October 2022. 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.

Study Overview

• Status: Completed
• Conditions: Renal Cell Carcinoma
• Intervention / Treatment: Drug: avelumab; Drug: axitinib

• Study Type: Observational
• Enrollment (Actual): 171

Contacts and Locations

Study Locations

• Japan
  • Fukuoka, Japan, 812-8582
    • Kyushu University Hospital
  • Hiroshima, Japan, 734-8551
    • Hiroshima University Hospital
  • Kyoto, Japan, 602-8566
    • University Hospital Kyoto Prefectural University of Medicine
  • Aichi
    • Nagoya, Aichi, Japan, 466-8560
      • Nagoya University Hospital
  • Aomori
    • Hirosaki, Aomori, Japan, 036-8563
      • Hirosaki University Hospital
  • Fukuoka
    • Kurume-shi, Fukuoka, Japan, 830-0011
      • Kurume University Hospital
  • Hokkaido
    • Asahikawa, Hokkaido, Japan, 078-8510
      • Asahikawa Medical University Hospital
    • Sapporo, Hokkaido, Japan, 060-8543
      • Sapporo Medical University Hospital
  • Hyogo
    • Kobe, Hyogo, Japan, 650-0017
      • Kobe University Hospital
    • Kobe-city, Hyogo, Japan, 650-0047
      • Kobe City Medical Center General Hospital
  • Ishikawa
    • Kanazawa-shi, Ishikawa, Japan, 920-8641
      • Kanazawa University Hospital
  • Kyoto
    • Kyoto-shi, Kyoto, Japan, 612-8555
      • National Hospital Organization Kyoto Medical Center
  • Kōchi
    • Nankoku, Kōchi, Japan, 783-8505
      • Kochi Medical School Hospital
  • Osaka
    • Osakasayama, Osaka, Japan, 589-8511
      • Kindai University Hospital
    • Suita-city, Osaka, Japan, 565-0871
      • Osaka University Hospital
  • Saitama
    • Saitama City, Saitama, Japan, 330-8503
      • Jichi Medical University Saitama Medical Center
  • Tokyo
    • Shinjuku-ku, Tokyo, Japan, 160-8582
      • Keio University Hospital
  • Wakayama
    • Wakayama-shi, Wakayama, Japan, 641-8510
      • Wakayama Medical University Hospital
  • Yamagata
    • Yamagata-Shi, Yamagata, Japan, 990-9585
      • Yamagata University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Patients with metastatic renal cell cancer(mRCC) treated with avelumab plus axitinib as a first-line therapy in Japan between 20 December 2019 and 17 October 2022

Description

Inclusion Criteria:

1. Diagnoses of mRCC based on the General Rule for Clinical and Pathological Studies on RCC (Fifth Edition) before receiving avelumab plus axitinib as first-line therapy. Patients with mRCC who have unresectable disease, either unresectable locally advanced or metastatic disease.
2. Age over 18 years at the time of the first administration of avelumab plus axitinib as firstline therapy for mRCC (baseline).
3. Index date from 20 December 2019 to 17 October 2022.

Exclusion Criteria:

1. Patients participating in a prospective interventional clinical trial assessing an investigational product during the observation period.
2. Patients (or a patient's legally representative) refusing to provide patient data during the consent process.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Retrospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Participants with metastatic renal cell carcinoma	Drug: avelumab; as provided in real world practice; Drug: axitinib; as provided in real world practice

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Age of Participants at Baseline	The age of participants at baseline was reported.	At Baseline (prior to initial treatment with avelumab plus axitinib)
Height of Participants at Baseline	The height of participants at baseline was reported.	At Baseline (prior to initial treatment with avelumab plus axitinib)
Body Weight of Participants at Baseline	The body weight of participants at baseline was reported.	At Baseline (prior to initial treatment with avelumab plus axitinib)
Body Mass Index of Participants at Baseline	The body mass index (BMI) of participants at baseline was reported.	At Baseline (prior to initial treatment with avelumab plus axitinib)
C-Reactive Protein Levels of Participants at Baseline	The C-reactive protein levels of participants at baseline was reported.	At Baseline (prior to initial treatment with avelumab plus axitinib)
Estimated Glomerular Filtration Rate of Participants at Baseline	The estimated Glomerular Filtration Rate (eGFR) is an index of kidney function. eGFR was calculated using factors such as serum creatinine level, age, sex, and in millimeter per minute per 1.73 square meter (ml/min/1.73 m^2), and tabulated in three categories (<60, ≥60, unknown). An eGFR <60 indicates some degree of kidney impairment. And eGFR > 60 is generally considered to be within the normal range.	At Baseline (prior to initial treatment with avelumab plus axitinib)
Smoking History Status of Participants at Baseline	The smoking history status of participants at baseline was reported.	At Baseline (prior to initial treatment with avelumab plus axitinib)
Eastern Cooperative Oncology Group (ECOG) Performance Scale Score Status of Participants at Baseline	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.	At Baseline (prior to initial treatment with avelumab plus axitinib)
Number of Participants With Metastatic Organs at Baseline	The Number of participants with Metastatic Organs of participants at baseline was reported.	At Baseline (prior to initial treatment with avelumab plus axitinib)
Invasion Depth (T Factor) of Participants at Baseline	TX: Primary tumor cannot be assessed, T0: No evidence of primary tumor, T1: Tumor ≤7 cm in greatest dimension, limited to the kidney, T1a: Tumor≤4cm in greatest dimension, limited to the kidney, T1b: Tumor>4 cm but ≤7 cm in greatest dimension, limited to the kidney, T2: Tumor >7 cm in greatest dimension, limited to the kidney, T2a: Tumor >7 cm but ≤10 cm in greatest dimension, limited to the kidney, T2b: Tumor >10 cm, limited to the kidney, T3: Tumor extends into major veins or perinephric tissues, but not into the ipsilateral adrenal gland and not beyond Gerota's fascia,T3a: Tumor extends into the renal vein or its segmental branches, or invades the pelvicalyceal system, or invades perirenal and, T3b: Tumor extends into the vena cava below the diaphragm, T3c: Tumor extends into the vena cava above the diaphragm or invades the wall of the vena cava, T4: Tumor invades beyond Gerota's fascia (including contiguous extension into the ipsilateral adrenal gland)	At Baseline (prior to initial treatment with avelumab plus axitinib)
Lymph Node Metastasis (N Factor) Status of Participants at Baseline	Lymph node metastasis (N factor) of participants at baseline was reported. NX: Regional lymph nodes cannot be assessed, N0: No regional lymph node metastasis, N1: Metastasis in regional lymph node(s).	At Baseline (prior to initial treatment with avelumab plus axitinib)
Distant Metastasis (M Factor) Status of Participants at Baseline	Distant metastasis (M factor) of participants at baseline was reported. M0: No distant metastasis, M1: Distant metastasis.	At Baseline (prior to initial treatment with avelumab plus axitinib)
Tumor Histological Type of Participants at Baseline	Tumor histological type of participants at baseline was reported.	At Baseline (prior to initial treatment with avelumab plus axitinib)
Number of Participants With Presence or Absence of Sarcomatoid Component in Participants at Baseline	Number of Participants with Presence or Absence of Sarcomatoid Component at baseline was reported.	At Baseline (prior to initial treatment with avelumab plus axitinib)
Fuhrman Grade Status of Participants at Baseline	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'.	At Baseline (prior to initial treatment with avelumab plus axitinib)
Availability of Proteinuria in Participants at Baseline	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) (Normal), positive (±) =15-29 mg/dL (increased risk for kidney disease), (1+) = 30 mg/dL(Early stages of kidney disease), (2+)= 100 mg/dL (Underlying kidney disease), (3+)= 300 mg/dL (kidney dysfunction).	At Baseline (prior to initial treatment with avelumab plus axitinib)
Performance of Nephrectomy in Participants	Performance of nephrectomy at baseline was reported.	At Baseline (prior to initial treatment with avelumab plus axitinib)
Number of Participants With Presence or Absence of Clinically Important Comorbidities of Participants at Baseline	Number of Participants with Presence or absence of clinically important comorbidities at baseline was reported.	At Baseline (prior to initial treatment with avelumab plus axitinib)
Number of Participants With Presence or Absence of Clinically Important Concomitant Drugs in Participants at Baseline	Number of participants with Presence or absence of clinically important concomitant drugs at baseline was reported.	At Baseline (prior to initial treatment with avelumab plus axitinib)
Number of Participants With Initiation of Systemic Therapy Within One Year of Diagnosis	Number of Participants with Initiation of Systemic Therapy within One Year of Diagnosis was reported.	At Baseline (prior to initial treatment with avelumab plus axitinib)
Number of Participants With Karnofsky Performance Status Less Than (<) 80 Percent (%) at Baseline	Karnofsky performance score was used to quantify participant's general well-being and activities of daily life and participants were classified based on their functional impairment. Karnofsky performance score ranges between 0 (death) to 100 (no evidence of disease). Higher score means higher ability to perform daily tasks.	At Baseline (prior to initial treatment with avelumab plus axitinib)
Number of Participants With Hemoglobin Value Below the Lower Normal Limit at Baseline	Number of participants with Hemoglobin value below the lower normal limit at baseline was reported.	At Baseline (prior to initial treatment with avelumab plus axitinib)
Number of Participants With Corrected Calcium Value Above the Upper Normal Limit in Participants at Baseline	Number of participants with Corrected calcium value above the upper normal limit at baseline was reported.	At Baseline (prior to initial treatment with avelumab plus axitinib)
Number of Participants With Neutrophil Count Above the Upper Normal Limit in Participants at Baseline	Number of Participants with Neutrophil count above the upper normal limit at baseline was reported.	At Baseline (prior to initial treatment with avelumab plus axitinib)
International Metastatic RCC Database Consortium (IMDC) Risk Group in Participants at Baseline	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: Low risk (0 factor), Medium risk (1-2 factors), High risk (more than or equal to [>=]3 factors).	At Baseline (prior to initial treatment with avelumab plus axitinib)
Number of Risk Factors in Participants at Baseline	Number of risk factors in participants at baseline was reported	At Baseline (prior to initial treatment with avelumab plus axitinib)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Real-World Progression-Free Survival (Rw-PFS)	rwPFS is defined as: The time from start of avelumab plus axitinib therapy to date of first disease progression (as clinically assessed by local investigator based on radiology, laboratory evidence, pathology, or other assessments) or death due to any cause, whichever occurred first.	From index date up to 31 Oct 2022, where index date was date of first prescription for avelumab plus axitinib between 20 December 2019 and 17 October 2022 (maximum observation period was of 34 months approximately)
Time to Treatment Discontinuation (TTD)	TTD is defined as the time from the start of treatment with avelumab plus axitinib to the end of treatment due to any cause except the effectiveness of the treatment.	From index date up to 31 Oct 2022, where index date was date of first prescription for avelumab plus axitinib between 20 December 2019 and 17 October 2022 (maximum observation period was of 34 months approximately)
Overall Survival (OS)	OS is defined as the time from the start of treatment with avelumab plus axitinib to the date of death due to any cause. If there are no clinical records of death, the date when the patient was last documented to be alive will be confirmed based on medical records. The data will be censored at the date of last contact.	From index date up to 31 Oct 2022, where index date was date of first prescription for avelumab plus axitinib between 20 December 2019 and 17 October 2022 (maximum observation period was of 34 months approximately)
Percentage of Participants With Best Overall Response of CR or PR (Objective Response Rate)	The ORR is defined as the proportion of participants with a documented BOR (complete response (CR) or partial response (PR)) by the investigator during treatment with avelumab plus axitinib as firstline therapy. The BOR is defined as the best tumor response recorded during the observation period. The definitions of tumor responses are as follows: Complete or PR as the best adjudication result (CR > PR > stable disease [SD] > progressive disease [PD], not Evaluable [NE]) complies with the RECIST tumor assessment guidelines as closely as possible in clinical practice.	From index date up to 31 Oct 2022, where index date was date of first prescription for avelumab plus axitinib between 20 December 2019 and 17 October 2022 (maximum observation period was of 34 months approximately)
Number of Participants With Best Overall Response (BOR) for Primary Lesions	BOR is the best tumor response recorded during observation period.Tumor response are defined as follows:Complete or PR as the best adjudication result (CR > PR > stable disease [SD] > progressive disease [PD],not Evaluable[NE]) in a method complied with RECIST version. 1.1tumor assessment as closely as possible in clinical practice by investigator's judgment.CR:Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR:Atleast 30% decrease in sum of diameters of target lesions,taking as reference the baseline sum diameters.SD:Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD,taking as reference the smallest sum diameters. PD:atleast a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study.In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5mm.	From index date up to 31 Oct 2022, where index date was date of first prescription for avelumab plus axitinib between 20 December 2019 and 17 October 2022 (maximum observation period was of 34 months approximately)

Collaborators and Investigators

• Sponsor: Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
• Investigators: Study Director: Medical Responsible, Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

Publications and helpful links

Helpful Links

• Trial Awareness and Transparency website

Study record dates

Study Major Dates

• Study Start (Actual): January 25, 2023
• Primary Completion (Actual): October 13, 2023
• Study Completion (Actual): October 13, 2023

Study Registration Dates

• First Submitted: December 6, 2022
• First Submitted That Met QC Criteria: December 6, 2022
• First Posted (Actual): December 14, 2022

Study Record Updates

• Last Update Posted (Actual): March 28, 2025
• Last Update Submitted That Met QC Criteria: March 27, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: Avelumab; Japan; Non-interventional; Multicenter; Retrospective; Axitinib; First-line therapy; Medical chart review; Metastatic renal cell cancer(mRCC); Standard care in real-world clinical setting
• Additional Relevant MeSH Terms: Urogenital Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Urologic Neoplasms; Kidney Neoplasms; Carcinoma; Carcinoma, Renal Cell; Antineoplastic Agents, Immunological; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; Avelumab; Axitinib
• Other Study ID Numbers: B9991052; J-DART2 (Other Identifier: Alias Study Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: We are committed to enhancing public health through responsible sharing of clinical trial data. Following approval of a new product or a new indication for an approved product in both the US and the European Union, the study sponsor and/or its affiliated companies will share study protocols, anonymized patient data and study level data, and redacted clinical study reports with qualified scientific and medical researchers, upon request, as necessary for conducting legitimate research. Further information on how to request data can be found on our website bit.ly/IPD21

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No