Study On Fatigue- And Hand-Foot Syndrome-Related Quality Of Life In Patients With Metastatic Renal Cell Carcinoma Receiving A Tyrosine Kinase Inhibitor as First-Line Treatment

Primary outcomes

1. Number of Participants Categorized According to the Napping Habits for All Participants at Baseline

   Time frame: Baseline

   In this outcome measure, number of participants were classified according to their habit of taking daytime rest (naps) as never, always and sometimes. Never is defined as someone who does not take any daytime nap, always is defined as someone who takes daytime naps daily and sometimes is defined as someone who takes daytime naps on weekends or on holidays.

2. Number of Participants Categorized According to the Napping Habits for All Participants at Week 12

   Time frame: Week 12

   In this outcome measure, number of participants were classified according to their habit of taking daytime rest (naps) as never, always and sometimes. Never is defined as someone who does not take any daytime nap, always is defined as someone who takes daytime naps daily and sometimes is defined as someone who takes daytime naps on weekends or on holidays.

3. Number of Participants Categorized According to the Napping Habits for All Participants at Week 24

   Time frame: Week 24

   In this outcome measure, number of participants were classified according to their habit of taking daytime rest (naps) as never, always and sometimes. Never is defined as someone who does not take any daytime nap, always is defined as someone who takes daytime naps daily and sometimes is defined as someone who takes daytime naps on weekends or on holidays.

4. Number of Participants Categorized According to the Napping Habits for All Participants at Week 36

   Time frame: Week 36

   In this outcome measure, number of participants were classified according to their habit of taking daytime rest (naps) as never, always and sometimes. Never is defined as someone who does not take any daytime nap, always is defined as someone who takes daytime naps daily and sometimes is defined as someone who takes daytime naps on weekends or on holidays.

5. Number of Participants Categorized According to Association Between the Practice of Aerobic Physical Exercise and Fatigue at Baseline

   Time frame: Baseline

   In this outcome measure, number of participants were classified according to the presence or absence of fatigue based on their habit of performing aerobic physical exercise as never, always and sometimes.

6. Number of Participants Categorized According to Association Between the Practice of Aerobic Physical Exercise and Fatigue at Week 12

   Time frame: Week 12

   In this outcome measure, number of participants were classified according to the presence or absence of fatigue based on their habit of performing aerobic physical exercise as never, always and sometimes.

7. Number of Participants Categorized According to Association Between the Practice of Aerobic Physical Exercise and Fatigue at Week 24

   Time frame: Week 24

   In this outcome measure, number of participants were classified according to the presence or absence of fatigue based on their habit of performing aerobic physical exercise as never, always and sometimes.

8. Number of Participants Categorized According to Association Between the Practice of Aerobic Physical Exercise and Fatigue at Week 36

   Time frame: Week 36

   In this outcome measure, number of participants were classified according to the presence or absence of fatigue based on their habit of performing aerobic physical exercise as never, always and sometimes.

9. Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score at Baseline

   Time frame: Baseline

   FACIT-F was a 13-item questionnaire which assessed self-reported fatigue and its impact upon daily activities and function. Participants responded to each item on a 5-point scale based on their experience of fatigue during the past 7 days (0= not at all; 1= a little bit; 2= somewhat; 3= quite a bit; 4= very much). FACIT-F score was calculated by summing the 13 items (range 0 [not at all] to 52 [very much]); higher scores represented less fatigue and better status of participants.

10. Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score at Week 6

    Time frame: Week 6

    FACIT-F was a 13-item questionnaire which assessed self-reported fatigue and its impact upon daily activities and function. Participants responded to each item on a 5-point scale based on their experience of fatigue during the past 7 days (0= not at all; 1= a little bit; 2= somewhat; 3= quite a bit; 4= very much). FACIT-F score was calculated by summing the 13 items (range 0 [not at all] to 52 [very much]); higher scores represented less fatigue and better status of participants.

11. Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score at Week 12

    Time frame: Week 12

    FACIT-F was a 13-item questionnaire which assessed self-reported fatigue and its impact upon daily activities and function. Participants responded to each item on a 5-point scale based on their experience of fatigue during the past 7 days (0= not at all; 1= a little bit; 2= somewhat; 3= quite a bit; 4= very much). FACIT-F score was calculated by summing the 13 items (range 0 [not at all] to 52 [very much]); higher scores represented less fatigue and better status of participants.

12. Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score at Week 18

    Time frame: Week 18

    FACIT-F was a 13-item questionnaire which assessed self-reported fatigue and its impact upon daily activities and function. Participants responded to each item on a 5-point scale based on their experience of fatigue during the past 7 days (0= not at all; 1= a little bit; 2= somewhat; 3= quite a bit; 4= very much). FACIT-F score was calculated by summing the 13 items (range 0 [not at all] to 52 [very much]); higher scores represented less fatigue and better status of participants.

13. Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score at Week 24

    Time frame: Week 24

    FACIT-F was a 13-item questionnaire which assessed self-reported fatigue and its impact upon daily activities and function. Participants responded to each item on a 5-point scale based on their experience of fatigue during the past 7 days (0= not at all; 1= a little bit; 2= somewhat; 3= quite a bit; 4= very much). FACIT-F score was calculated by summing the 13 items (range 0 [not at all] to 52 [very much]); higher scores represented less fatigue and better status of participants.

14. Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score at Week 30

    Time frame: Week 30

    FACIT-F was a 13-item questionnaire which assessed self-reported fatigue and its impact upon daily activities and function. Participants responded to each item on a 5-point scale based on their experience of fatigue during the past 7 days (0= not at all; 1= a little bit; 2= somewhat; 3= quite a bit; 4= very much). FACIT-F score was calculated by summing the 13 items (range 0 [not at all] to 52 [very much]); higher scores represented less fatigue and better status of participants.

15. Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score at Week 36

    Time frame: Week 36

    FACIT-F was a 13-item questionnaire which assessed self-reported fatigue and its impact upon daily activities and function. Participants responded to each item on a 5-point scale based on their experience of fatigue during the past 7 days (0= not at all; 1= a little bit; 2= somewhat; 3= quite a bit; 4= very much). FACIT-F score was calculated by summing the 13 items (range 0 [not at all] to 52 [very much]); higher scores represented less fatigue and better status of participants.

16. Number of Participants Classified According to Time of Taking Treatment at Week 1

    Time frame: Week 1

    In this outcome measure, the number of participants were classified on the basis of the time of taking the oral medication - "morning, afternoon or night". Morning was anytime between 7 am to 12 pm. Afternoon was anytime between 1 pm and 7 pm. Night was anytime between 8 pm to 6 am. Participants who did not take medication were also classified.

17. Number of Participants Classified According to Time of Taking Treatment at Week 6

    Time frame: Week 6

    In this outcome measure, the number of participants were classified on the basis of the time of taking the oral medication - "morning, afternoon or night". Morning was anytime between 7 am to 12 pm. Afternoon was anytime between 1 pm and 7 pm. Night was anytime between 8 pm to 6 am. Participants who did not take medication were also classified.

18. Number of Participants Classified According to Time of Taking Treatment at Week 12

    Time frame: Week 12

    In this outcome measure, the number of participants were classified on the basis of the time of taking the oral medication - "morning, afternoon or night". Morning was anytime between 7 am to 12 pm. Afternoon was anytime between 1 pm and 7 pm. Night was anytime between 8 pm to 6 am. Participants who did not take medication were also classified.

19. Number of Participants Classified According to Time of Taking Treatment at Week 18

    Time frame: Week 18

    In this outcome measure, the number of participants were classified on the basis of the time of taking the oral medication - "morning, afternoon or night". Morning was anytime between 7 am to 12 pm. Afternoon was anytime between 1 pm and 7 pm. Night was anytime between 8 pm to 6 am. Participants who did not take medication were also classified.

20. Number of Participants Classified According to Time of Taking Treatment at Week 24

    Time frame: Week 24

    In this outcome measure, the number of participants were classified on the basis of the time of taking the oral medication - "morning, afternoon or night". Morning was anytime between 7 am to 12 pm. Afternoon was anytime between 1 pm and 7 pm. Night was anytime between 8 pm to 6 am. Participants who did not take medication were also classified.

21. Number of Participants Classified According to Time of Taking Treatment at Week 30

    Time frame: Week 30

    In this outcome measure, the number of participants were classified on the basis of the time of taking the oral medication - "morning, afternoon or night". Morning was anytime between 7 am to 12 pm. Afternoon was anytime between 1 pm and 7 pm. Night was anytime between 8 pm to 6 am. Participants who did not take medication were also classified.

22. Number of Participants Classified According to Time of Taking Treatment at Week 36

    Time frame: Week 36

    In this outcome measure, the number of participants were classified on the basis of the time of taking the oral medication - "morning, afternoon or night". Morning was anytime between 7 am to 12 pm. Afternoon was anytime between 1 pm and 7 pm. Night was anytime between 8 pm to 6 am. Participants who did not take medication were also classified.

23. Number of Participants Categorized According to Number of Changes to Dose Per Treatment Cycle During 9 Months of Follow-up

    Time frame: During 9 months

    In this outcome measure, number of participants were classified according to the number of changes to dose that is (i.e). 0, 1 or 2 occurred per treatment cycle during 9 months of follow-up.

24. Number of Participants Categorized According to Number of Interruptions to Dose Occurred in Each Treatment Cycle During 9 Months of Follow-up

    Time frame: During 9 months

    In this outcome measure, number of participants were classified according to the number of interruptions to dose i.e. 0, 1, 2, 3 or 4 occurred in each treatment cycle during 9 months follow-up.

25. Number of Participants With Best Response Per Response Evaluation Criteria for Solid Tumours Version 1.1. (RECIST v1.1)

    Time frame: From start of treatment with TKI until first documented best response of CR, PR, SD or DP (approximately maximum up to 3.8 years)

    Best response was recorded from start of treatment with TKI until best complete response (CR), partial response (PR), stable disease (SD) or disease progression (DP) was achieved. RECIST v1.1, a) CR: disappearance of all lesions; any pathological lymph nodes (target lesions [TLs]) or non-target lesions (non-TLs) must have reduction in short axis to <10 mm; normalization of tumor marker level for non-TLs; b) PR: >=30% decrease in sum of diameter of all TLs, taking as reference baseline sum of diameters; c) DP: >=20% increase in sum of diameter of all TLs, taking as reference the smallest sum on study (including baseline measurement), sum must also be absolute increase of >=5 mm. Unequivocal progression of existing non TLs. Appearance of at least 1 new lesion; d) SD: neither sufficient shrinkage to qualify for PR nor sufficient increase in lesions to qualify for PD referring smallest sum diameter. Participant whose best response was not determined were classified as "Undetermined".

26. Mean Duration of Treatment

    Time frame: From start of treatment till end of treatment (approximately maximum up to 3.8 years)

    In this outcome measure, the mean duration of treatment was calculated and reported below.

27. Time to Treatment Failure (TTF) After Initiation of Tyrosine Kinase Inhibitor Therapy

    Time frame: From start of treatment with a TKI to tumour progression, treatment discontinuation for any reason or death from any cause or till follow-up in case of no event (approximately maximum up to 3.8 years)

    TTF was defined as the time from the start of treatment with a TKI to tumour progression, treatment discontinuation for any reason or death from any cause. Participants who did not had the event were censored on the date of their final follow-up. Per RECIST 1.1, tumour progression: >=20% increase in sum of diameter of all measured target lesions, taking as reference smallest sum on study (including baseline measurement) of diameter of all target lesions, sum must also demonstrate an absolute increase of >=5 mm. Unequivocal progression of existing non target lesions. Appearance of at least 1 new lesion.

28. Number of Participants Categorized According to Number of Treatment Cycles Received

    Time frame: From start of treatment till end of treatment (approximately maximum up to 3.8 years)

    In this outcome measure, number of participants were classified according to number of treatment cycles received.

29. Progression-Free Survival (PFS)

    Time frame: From start of treatment with a TKI to tumour progression or death for any reason or till follow-up in case of no event (approximately maximum up to 3.8 years)

    PFS was defined as the time from the start of treatment with a TKI to tumour progression or death for any reason. Participants who, did not had the event were censored on the date of their final follow-up. Per RECIST v1.1, tumour progression: >=20% increase in sum of diameter of all measured target lesions, taking as reference smallest sum on study (including baseline measurement) of diameter of all target lesions, sum must also demonstrate an absolute increase of >=5 mm. Unequivocal progression of existing non target lesions. Appearance of at least 1 new lesion.

30. Objective Response Rate (ORR)

    Time frame: From start of treatment with TKI until first documented CR or PR (approximately maximum up to 3.8 years)

    ORR was defined as the percentage of participants who achieved CR or PR. Per RECIST V1.1, a) CR: disappearance of all lesions; any pathological lymph nodes (target lesions or non-target lesions) must have reduction in short axis to <10 mm; normalization of tumor marker level for non-TLs; b) PR: >=30% decrease in sum of diameter of all target lesions, taking as reference baseline sum of diameters.

31. Duration of Response (DOR)

    Time frame: From day of documented CR or PR to the first day that DP was observed (approximately maximum up to 3.8 years)

    In participants who achieved CR or PR, DOR was defined as the duration from the documentation date of CR or PR to the first day when DP was observed. Per RECIST V1.1, a) CR: disappearance of all lesions; any pathological lymph nodes (target lesions or non-target lesions must have reduction in short axis to <10 mm; normalization of tumor marker level for non-target lesions; b) PR: >=30% decrease in sum of diameter of all target lesions, taking as reference baseline sum of diameters; c) DP: >=20% increase in sum of diameter of all measured target lesions, taking as reference smallest sum on study (including baseline measurement), sum must also demonstrate an absolute increase of >=5 mm. Unequivocal progression of existing non TLs. Appearance of at least 1 new lesion.

32. Number of Participants With Fatigue Event Graded Per Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0

    Time frame: During 9 months

    An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. As per CTCAE version 4, Grade 1= mild AE; Grade 2= moderate AE; Grade 3= severe AE; Grade 4= life-threatening or disabling AE; Grade 5= death related to an AE. In this outcome measure number of participants with fatigue event were classified into following: CTCAE grade 1 to 2 and CTCAE grade 3 to 4.

33. Number of Participants With Hand Foot Syndrome Event Graded Per Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0

    Time frame: During 9 months

    An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. As per CTCAE version 4, Grade 1= mild AE; Grade 2= moderate AE; Grade 3= severe AE; Grade 4= life-threatening or disabling AE; Grade 5= death related to an AE. In this outcome measure number of participants with hand foot syndrome event were classified into following: CTCAE grade 1 to 2 and CTCAE grade 3 to 4.

34. Number of Participants With Palmar-Plantar Erythrodysaesthesia (HFS) Event Graded Per CTCAE Version 4.0 at Week 12

    Time frame: Week 12

    AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. As per CTCAE version 4, Grade 1= mild AE; Grade 2= moderate AE; Grade 3= severe AE; Grade 4= life-threatening or disabling AE; Grade 5= death related to an AE. In this outcome measure number of participants with HFS event graded per CTCAE version 4.0 at Week 12 are reported.

35. Number of Participants With Palmar-Plantar Erythrodysaesthesia (HFS) Event Graded Per CTCAE Version 4.0 at Week 24

    Time frame: Week 24

    AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. As per CTCAE version 4, Grade 1= mild AE; Grade 2= moderate AE; Grade 3= severe AE; Grade 4= life-threatening or disabling AE; Grade 5= death related to an AE. In this outcome measure number of participants with HFS event graded per CTCAE version 4.0 at Week 24 are reported.

36. Number of Participants With Palmar-Plantar Erythrodysaesthesia (HFS) Event Graded Per CTCAE Version 4.0 at Week 36

    Time frame: Week 36

    AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. As per CTCAE version 4, Grade 1= mild AE; Grade 2= moderate AE; Grade 3= severe AE; Grade 4= life-threatening or disabling AE; Grade 5= death related to an AE. In this outcome measure number of participants with HFS event graded per CTCAE version 4.0 at Week 36 are reported.