An Observational Study to Evaluate the Efficacy and Safety of Avelumab + Axitinib Combination in Participants With aRCC (AVION)

Overall survival rate was defined as the percentage of participants who are alive at 12 months after the index date. Percentage of participants alive at the time of outcome assessment (12 months) were calculated as per the Kaplan-Meier (KM) approach. The index date (baseline visit) was defined as the date of first administration after obtaining informed consent of avelumab plus axitinib therapy to participants with advanced RCC.

Overall survival rate was defined as the percentage of participants who are alive at 24 months after the index date. Percentage of participants alive at the time of outcome assessment (24 months) were calculated as per the Kaplan-Meier (KM) approach. The index date (baseline visit) was defined as the date of first administration after obtaining informed consent of avelumab plus axitinib therapy to participants with advanced RCC.

Duration of overall survival is defined as the time from index date to the date of death due to any cause. The overall survival was analyzed by using the Kaplan-Meier method. The index date (baseline visit) was defined as the date of first administration after obtaining informed consent of avelumab plus axitinib therapy to participants with advanced RCC.

Objective response rate was defined as percentage of participants with either a confirmed complete response (CR) or partial response (PR) as best overall response up to 24 months after the index date. CR: Disappearance of all target and non-target lesions. PR: At least a 30 percent (%) decrease in the sum of diameters of target lesions, taking as reference the baseline sum of their diameters, and no unequivocal progression of non-target lesions. The index date (baseline visit) was defined as the date of first administration after obtaining informed consent of avelumab plus axitinib therapy to participants with advanced RCC.

Disease control rate is defined as the percentage of participants with objective response (complete response [CR] or partial response [PR] or stable disease [SD]) as best overall response up to 24 months after the index date. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30 percent (%) reduction from baseline in the sum of the longest diameter (SLD) of all lesions. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest SLD while on study. PD is defined as at least a 20 % increase in the SLD of target lesion, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. The index date (baseline visit) was defined as the date of first administration after obtaining informed consent of avelumab plus axitinib therapy to participants with advanced RCC.

DoR was defined for participants with objective response, as the time from first documentation of objective response (Complete Response [CR] or Partial Response [PR]) to the date of first documentation of progression disease (PD) or death due to any cause, whichever occurred first. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30 percent (%) reduction from baseline in the sum of the longest diameter (SLD) of all lesions. PD was defined as at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. The index date (baseline visit) was defined as the date of first administration after obtaining informed consent of avelumab plus axitinib therapy to participants with advanced RCC.

PFS time was defined as the time from index date to the date of the first documentation of objective progressive disease (PD) or death due to any cause, whichever occurred first. Per RECIST version 1.1, PD was defined as at least a 20 percent (%) increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimeter (mm). The appearance of one or more new lesions was also considered PD. The tumor response was determined according to RECIST version 1.1 and assessed by the investigator. PFS was calculated based on KM method. The index date (baseline visit) was defined as the date of first administration after obtaining informed consent of avelumab plus axitinib therapy to participants with advanced RCC.

PFS2 was defined as time interval from the index date to the date of disease progression on second-line treatment or death from any cause, whichever occurred first. Per RECIST version 1.1, PD was defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered PD. The tumor response will be determined according to RECIST version 1.1 and assessed by the investigator. PFS2 was calculated based on Kaplan Meier method. The index date (baseline visit) was defined as the date of first administration after obtaining informed consent of avelumab plus axitinib therapy to participants with advanced RCC.

NCCN-FACT FKSI-19, a validated, disease-specific questionnaire for RCC. It includes 19 items across four domains, Disease-Related Symptoms-Physical (DRS-P), Disease-Related Symptoms-Emotional (DRS-E), Treatment Side Effects (TSE), and Functional Wellbeing (FWB), based on symptoms experienced over past 7 days. Responses were recorded on 5-point Likert scale (0 = not at all to 4 = very much), yielding a total score from 0 to 76, higher scores reflecting better quality of life. A negative mean change in score indicated worsening condition. Domain score ranges and directionality: DRS-P: 0-48, higher scores = fewer physical symptoms; DRS-E: 0-4, higher = fewer emotional symptoms; TSE: 0-12, higher = more severe side effects; FWB: 0-12, higher = better functional wellbeing. As per NCCN-FACT FKSI-19 scoring guidelines, the total Health-related quality of life (HRQoL) score (range 0-76) was calculated as sum of single items scores multiplied by 19 and divided by the number of items completed.

An adverse event (AE) is defined as any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study intervention, whether considered related to the study intervention or not. A serious AE was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAEs were defined as events with onset date or worsening during the on-treatment period. TEAEs included both serious and non-serious TEAEs. Treatment-related TEAEs is defined as reasonably related to the study intervention. The index date (baseline visit) was defined as the date of first administration after obtaining informed consent of avelumab plus axitinib therapy to participants with advanced RCC.

Severity of TEAEs were evaluated using the NCI-CTCAE version 5.0. The grade are as follows: grade 1 : mild grade 2 : moderate grade 3 : severe or medically significant but not immediately life-threatening grade 4 : life threatening or disabling grade 5 : death related to AE. Number of participants with TEAEs grade greater than or equal to (>=) 3 were reported. The index date (baseline visit) was defined as the date of first administration after obtaining informed consent of avelumab plus axitinib therapy to participants with advanced RCC.

Time to therapy discontinuation due to AE >= grade 3 was reported. The index date (baseline visit) was defined as the date of first administration after obtaining informed consent of avelumab plus axitinib therapy to participants with advanced RCC.

The index date (baseline visit) was defined as the date of first administration after obtaining informed consent of avelumab plus axitinib therapy to participants with advanced RCC. Duration of Avelumab plus Axitinib therapy (days) = (Date of discontinuation of Axitinib - Date of index date + 1). Duration of avelumab plus axitinib therapy among participants who discontinued the Axitinib due to all-cause AEs >= grade 3 was reported.

Time to onset of TEAE = Start date TEAE - Index date. The index date (baseline visit) was defined as the date of first administration after obtaining informed consent of avelumab plus axitinib therapy to participants with advanced RCC.

Duration of TEAE = (Stop date of TEAE - Start date of TEAE + 1) divided by 7. The index date (baseline visit) was defined as the date of first administration after obtaining informed consent of avelumab plus axitinib therapy to participants with advanced RCC.

Percentage of participants with therapy modifications due to AE related to avelumab plus axitinib therapy were reported. The index date (baseline visit) was defined as the date of first administration after obtaining informed consent of avelumab plus axitinib therapy to participants with advanced RCC.

Number of participants with different types of medical intervention or medications used for the management of TEAE related to avelumab plus axitinib therapy (e.g., use of corticosteroids, antihypertensive therapy, treatment for thyroid dysfunction, measures to decrease hemoglobin, and hematocrit) was reported. The index date (baseline visit) was defined as the date of first administration after obtaining informed consent of avelumab plus axitinib therapy to participants with advanced RCC.

Percentage of participants receiving later-line therapy were reported. The index date (baseline visit) was defined as the date of first administration after obtaining informed consent of avelumab plus axitinib therapy to participants with advanced RCC.

Time to second line treatment was calculated as: (second line treatment start date - last dose of Avelumab plus Axitinib + 1)/30.4375.

Number of participants with patient-reported potential signs and symptoms of immune-related AEs were reported. The index date (baseline visit) was defined as the date of first administration after obtaining informed consent of avelumab plus axitinib therapy to participants with advanced RCC.