Post Marketing Surveillance Study to Observe Safety and Efficacy of Inlyta in South Korea

Primary outcomes

1. Number of Participants With Adverse Events (AEs), Adverse Drug Reactions (ADRs), Serious Adverse Events (SAEs) and Serious Adverse Drug Reactions (SADRs)

   Time frame: From first dose of Inlyta or time of the participant's informed consent through the end of the observation period of the study, which included at least 28 calendar days post last dose of drug under study (observation period for the study was of 9 years)

   An AE was any untoward medical occurrence in a participant administered a medicinal or nutritional product (including pediatric formulas) without regard to possibility of a causal relationship with product treatment or usage. SAE was any untoward medical occurrence that at any dose resulted in death; was life-threatening; required inpatient hospitalization or prolongation of hospitalization; resulted in persistent or significant disability/incapacity; congenital anomaly/birth defect. An ADR was any untoward medical occurrence attributed to Inlyta in a participant who received Inlyta. SADR was an ADR resulting in any of the following outcomes or deemed significant for any other reason: death; life-threatening experience; initial or prolonged inpatient hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect. Relatedness to Inlyta was assessed by the physician.

2. Number of Participants With Unexpected AEs, Unexpected SAEs, Unexpected ADRs and Unexpected SADRs

   Time frame: From first dose of Inlyta or time of the participant's informed consent through the end of the observation period of the study, which included at least 28 calendar days post last dose of drug under study (observation period for the study was of 9 years)

   An AE was any untoward medical occurrence in a participant administered a medicinal or nutritional product (including pediatric formulas) without regard to possibility of a causal relationship with product treatment or usage. SAE was any untoward medical occurrence that at any dose resulted in death; was life-threatening; required inpatient hospitalization or prolongation of hospitalization; resulted in persistent or significant disability/incapacity; congenital anomaly/birth defect. An ADR was any untoward medical occurrence attributed to Inlyta in a participant who received Inlyta. SADR was any SAE that is attributed to Inlyta. Relatedness to Inlyta was assessed by the physician. An unexpected AE was an AE with a difference in nature, severity, specificity, or outcome, compared to the product licensure/safety notification of the drug. Unexpected ADRs were unexpected AEs that were, in the investigator's opinion, of causal relationship to the study treatment.

3. Duration of Adverse Events

   Time frame: From first dose of Inlyta or time of the participant's informed consent through the end of the observation period of the study, which included at least 28 calendar days post last dose of drug under study (observation period for the study was of 9 years)

4. Number of Participants With Adverse Events by Their Severity

   Time frame: From first dose of Inlyta or time of the participant's informed consent through the end of the observation period of the study, which included at least 28 calendar days post last dose of drug under study (observation period for the study was of 9 years)

   An AE was any untoward medical occurrence in a participant administered a medicinal or nutritional product (including pediatric formulas) without regard to possibility of a causal relationship with product treatment or usage. Severity was graded using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0 where, Grade 1: mild; Grade 2: moderate; Grade 3:severe or medically significant; Grade 4: life-threatening consequences; Grade 5: death related to AE. One participant may experience more than one event hence, one participant may be included in more than one category specified below.

5. Number of Participants With Adverse Events by Their Outcome

   Time frame: From first dose of Inlyta or time of the participant's informed consent through the end of the observation period of the study, which included at least 28 calendar days post last dose of drug under study (observation period for the study was of 9 years)

   An AE was any untoward medical occurrence in a participant administered a medicinal or nutritional product (including pediatric formulas) without regard to possibility of a causal relationship with product treatment or usage. The outcomes of AE included recovered, recovered with sequelae, recovering, not recovered and unknown. One participant may experience more than one event hence one participant may be included in more than one category specified below.

6. Number of Participants With Adverse Events by Their Seriousness Criteria

   Time frame: From first dose of Inlyta or time of the participant's informed consent through the end of the observation period of the study, which included at least 28 calendar days post last dose of drug under study (observation period for the study was of 9 years)

   An AE was any untoward medical occurrence in a participant administered a medicinal or nutritional product (including pediatric formulas) without regard to possibility of a causal relationship with product treatment or usage. The seriousness criteria for AEs included results in death, is life-threatening, requires inpatient hospitalization or prolongation of hospitalization, results in persistent or significant disability/incapacity, results in congenital anomaly/birth defect, other important medical event.

7. Number of Participants With Adverse Events by Their Causality to Inlyta

   Time frame: From first dose of Inlyta or time of the participant's informed consent through the end of the observation period of the study, which included at least 28 calendar days post last dose of drug under study (observation period for the study was of 9 years)

   An AE was any untoward medical occurrence in a participant administered a medicinal or nutritional product (including pediatric formulas) without regard to possibility of a causal relationship. The causality of AEs to Inlyta were assessed by physician according to the following criteria: certain, probable/likely, possible, unlikely, conditional/unclassified and unaccessible/unclassifiable. One participant may experience more than one event hence, one participant may be included in more than one category specified below.

8. Number of Participants With Adverse Events by Their Other Causality

   Time frame: From first dose of Inlyta or time of the participant's informed consent through the end of the observation period of the study, which included at least 28 calendar days post last dose of drug under study (observation period for the study was of 9 years)

   An AE was any untoward medical occurrence in a participant administered a medicinal or nutritional product (including pediatric formulas) without regard to possibility of a causal relationship with product treatment or usage. If the AEs were not related to Inlyta, physicians were required to indicate the most appropriate cause of AEs from the following: disease under the study, other disease, concomitant treatment drug or non-drug and others.

9. Number of Participants With Adverse Events by Their Action Taken With Study Drug

   Time frame: From first dose of Inlyta or time of the participant's informed consent through the end of the observation period of the study, which included at least 28 calendar days post last dose of drug under study (observation period for the study was of 9 years)

   An AE was any untoward medical occurrence in a participant administered a medicinal or nutritional product (including pediatric formulas) without regard to possibility of a causal relationship with product treatment or usage. The action taken with study drug due to AEs included discontinuation, dosage reduced, no change, unknown and not applicable. One participant may experience more than one event hence, one participant may be included in more than one category specified below.

10. Number of Participants With Adverse Events According to Demographic Characteristics

    Time frame: From first dose of Inlyta or time of the participant's informed consent through the end of the observation period of the study, which included at least 28 calendar days post last dose of drug under study (observation period for the study was of 9 years)

    An AE was any untoward medical occurrence in a participant administered a medicinal or nutritional product (including pediatric formulas) without regard to possibility of a causal relationship with product treatment or usage. Number of participants with AEs classified according to the following demographic characteristics: sex: male and female; age: less than (<) 60 years, greater than or equal to (>=) 60 and < 70 years and >= 70 years; pediatric (<19 years); geriatric (>=65 years); classification: outpatient and inpatient were reported in the outcome measure.

11. Number of Participants With Adverse Events According to Other Baseline Characteristics

    Time frame: From first dose of Inlyta or time of the participant's informed consent through the end of the observation period of the study, which included at least 28 calendar days post last dose of drug under study (observation period for the study was of 9 years)

    An AE was any untoward medical occurrence in a participant administered a medicinal or nutritional product (including pediatric formulas) without regard to possibility of a causal relationship with product treatment or usage. Number of participants with AEs classified according to the following characteristics: duration of aRCC: < 30 months, >= 30 months and < 60 months,>= 60 months; cell component of aRCC : clear cell ,other; metastasis: yes,no; site of metastasis: liver, lung, bone, brain, skin, lymph nodes, other; primary lesion surgery: done and not done; medical history: yes and no; renal impairment: yes and no; hepatic impairment: yes and no; allergic history: yes and no; prior chemotherapy: yes and no; prior immunotherapy: yes and no; prior radiation therapy: yes and no; concomitant medication: yes and no; duration of administration: < 90 days, >=90 and <180 days and >= 180 days; daily average dose: <10 and >=10 milligrams per day (mg/day).

12. Number of Participants With Adverse Events - Multivariate Logistic Regression Analysis

    Time frame: From first dose of Inlyta or time of the participant's informed consent through the end of the observation period of the study, which included at least 28 calendar days post last dose of drug under study (observation period for the study was of 9 years)

    An AE was any untoward medical occurrence in a participant administered a medicinal or nutritional product (including pediatric formulas) without regard to possibility of a causal relationship with product treatment or usage.

13. Number of Participants With AEs and ADRs - Special Participant Population

    Time frame: From first dose of Inlyta or time of the participant's informed consent through the end of the observation period of the study, which included at least 28 calendar days post last dose of drug under study (observation period for the study was of 9 years)

    An AE was any untoward medical occurrence in a participant administered a medicinal or nutritional product (including pediatric formulas) without regard to possibility of a causal relationship with product treatment or usage. An ADR was any untoward medical occurrence attributed to Inlyta in a participant who received Inlyta.

14. Number of Participants With Tumor Response Based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1

    Time frame: From first dose of Inlyta up to first documented CR, PR, PD or SD, during observation period of the study of 9 years

    Tumor response based on RECIST 1.1 was defined as: complete response (CR): complete disappearance of all target and non-target lesions. All lymph nodes must be non-pathological in size (<10 mm short axis); partial response (PR): at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters; progressive disease (PD): at least 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 5 mm or unequivocal progression of existing non-target lesions. The appearance of one or more new lesions is also considered a sign of progression; stable disease (SD): neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study and not done.

15. Number of Participants With Objective Response

    Time frame: From first dose of Inlyta up to first documented CR or PR, during observation period of the study of 9 years

    Objective response (OR) was defined as the achievement of partial or complete response to therapy based on RECIST 1.1. CR: complete disappearance of all target and non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (<10 mm short axis). PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

16. Number of Participants With Objective Response According to Demographic Characteristics

    Time frame: From first dose of Inlyta up to first documented CR or PR, during observation period of the study of 9 years

    OR was defined as the number of participants who have a partial or complete response to therapy. CR: complete disappearance of all target and non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (<10 mm short axis). PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Number of participants with objective response categorized according to the following demographic characteristics was presented in this outcome measure: sex: male and female; age: < 60 years, >= 60 and < 70 years, >= 70 years; pediatric (<19 years); geriatric (>=65 years); classification: outpatient and inpatient.

17. Number of Participants With Objective Response According to Other Baseline Characteristics

    Time frame: From first dose of Inlyta up to first documented CR or PR, during observation period of the study of 9 years

    OR was defined as the number of participants who have a partial or complete response to therapy. Number of participants with OR classified according to the following characteristics included duration of aRCC: < 30 months, >= 30 months and < 60 months and >= 60 months; cell component of aRCC : clear cell and other; metastasis: yes and no; site of metastasis: liver, lung, bone, brain, skin, lymph nodes and other; primary lesion surgery: done and not done; medical history: yes and no; renal impairment: yes and no; hepatic impairment: yes and no; allergic history: yes and no; prior chemotherapy: yes and no; prior immunotherapy: yes and no; prior radiation therapy: yes and no; concomitant medication: yes and no; duration of administration: < 90 days, >=90 and <180 days and >= 180 days; daily average dose: <10 and >=10 mg/day.

18. Number of Participants With Objective Response - Multivariate Logistic Regression Analysis

    Time frame: From first dose of Inlyta up to first documented CR or PR, during observation period of the study of 9 years

    OR was defined as the achievement of partial or complete response to therapy based on RECIST 1.1. CR: complete disappearance of all target and non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (<10 mm short axis). PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

19. Progression Free Survival (PFS)

    Time frame: From first dose of Inlyta up to first documented tumor progression or death, whichever occurred first, during observation period of the study of 9 years

    PFS was defined as the time from first dose of Inlyta to first documentation of objective tumor progression, or to death due to any cause, whichever occurred first. Tumor progression was determined from tumor assessment criteria(where data meet the criteria for progressive disease [PD]), or from death report on case report forms (CRFs). PD: at least 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 5 mm or unequivocal progression of existing non-target lesions. The appearance of one or more new lesions is also considered a sign of progression.

20. Time to Progression (TTP)

    Time frame: From first dose of Inlyta up to first documented disease progression or latest follow-up, during observation period of the study of 9 years

    TTP was defined as the time from the start of Inlyta treatment to date of disease progression. If there was no progression, the case was censored as TTP at latest follow-up. Disease progression was defined as >20% increase in sum of longest diameter of target lesions compared to baseline.