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

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'.

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).

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'.

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.

In this outcome measure, participants were categorized as "Yes" or "No" according to presence of sarcomatoid component were reported.

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.

In this outcome measure participants were reported according to number of metastatic organs as a) 1 and, b) 2 or more.

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.

In this outcome measure participants were reported as "Yes" or "No" according to presence of complications.

In this outcome measure, participants who underwent nephrectomy previously, were reported as "Yes' or "No".

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).

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.

CRP was a laboratory measurement for evaluation of an acute phase reactant of inflammation through the use of an ultra-sensitive assay.

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".

In this outcome measure, participants who took concomitant drugs were reported.

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.

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.

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.

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.

In this outcome measure, number of participants who discontinued and had interruption of avelumab and axitinib treatment were reported.

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.

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.

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.

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.

In this outcome measure, participants who had dose modification (increase/decrease) were reported.

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.

Immune-related adverse events (irAEs) was defined as the serious side effect of immune checkpoint inhibitor therapy for participants with advanced cancer.

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.

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.

In this outcome measure, number of participants who received any treatment for infusion-related reaction of avelumab were reported.

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.