Observational Study Evaluating The Efficacy And Effects On Quality Of Life Of Targeted Treatments Following TKIs In mRCC

PFS was defined as the time duration (in months) during and after the treatment of disease that a participant lived with the disease but it did not get worse or progressed. Progressive disease as per response evaluation criteria in solid tumors (RECIST) version 1.1 defined as at least a 20 percent (%) increase in the sum of longest dimensions of target lesions, reference to the smallest sum of the longest dimensions recorded since the treatment started, or the appearance of one or more new lesions or increase of at least 5 millimeter (mm) in addition to the relative increase of 20%.

Overall objective response was defined as the percentage of participants with best confirmed response (partial response [PR], stable disease [SD] or progressive disease [PD]) recorded from the start of the study treatment until the end of treatment as assessed by RECIST version 1.1. PR defined as a 30% or more decrease in the sum of longest dimensions of the target lesions, taking as reference the baseline sum of longest dimensions. PD defined as at least a 20% increase in the sum of longest dimensions of target lesions, reference to the smallest sum of the longest dimensions recorded since the treatment started, or the appearance of one or more new lesions or increase of at least 5 mm in addition to the relative increase of 20%. SD defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, reference to the smallest sum diameters while on study.

FKSI was used to assess quality of life (QoL) of the participants and consisted of 15 items (lack of energy, side effects, pain, losing weight, bone pain, fatigue, enjoying life, short of breath, worsened condition, appetite, coughing, bothered by fevers, ability to work, hematuria and sleep). Each of the 15 items was answered on a 5-point Likert scale ranging from 0 to 4 (0= not at all, 1= a little bit, 2= somewhat, 3= quite a bit, 4= very much). Total FKSI score = sum of the 15 item scores; total range: 0 - 60; 0 (no symptoms) to 60 (very much); higher score indicated greater presence of symptoms/worse quality of life.

FKSI was used to assess QoL of the participants and consisted of 15 items (lack of energy, side effects, pain, losing weight, bone pain, fatigue, enjoying life, short of breath, worsened condition, appetite, coughing, bothered by fevers, ability to work, hematuria and sleep). Each of the 15 items was answered on a 5-point Likert scale ranging from 0 to 4 (0= not at all, 1= a little bit, 2= somewhat, 3= quite a bit, 4= very much). Total FKSI score = sum of the 15 item scores; total range: 0 - 60; 0 (no symptoms) to 60 (very much); higher score indicated greater presence of symptoms/worse quality of life.

FKSI was used to assess quality of life (QoL) of the participants and consisted of 15 items (lack of energy, side effects, pain, losing weight, bone pain, fatigue, enjoying life, short of breath, worsened condition, appetite, coughing, bothered by fevers, ability to work, hematuria and sleep). Each of the 15 items was answered on a 5-point Likert scale ranging from 0 to 4 (0= not at all, 1= a little bit, 2= somewhat, 3= quite a bit, 4= very much). Total FKSI score = sum of the 15 item scores; total range: 0 - 60; 0 (no symptoms) to 60 (very much); higher score indicated greater presence of symptoms/worse quality of life.

FKSI was used to assess quality of life (QoL) of the participants and consisted of 15 items (lack of energy, side effects, pain, losing weight, bone pain, fatigue, enjoying life, short of breath, worsened condition, appetite, coughing, bothered by fevers, ability to work, hematuria and sleep). Each of the 15 items was answered on a 5-point Likert scale ranging from 0 to 4 (0= not at all, 1= a little bit, 2= somewhat, 3= quite a bit, 4= very much). Total FKSI score = sum of the 15 item scores; total range: 0 - 60; 0 (no symptoms) to 60 (very much); higher score indicated greater presence of symptoms/worse quality of life.

FKSI was used to assess quality of life (QoL) of the participants and consisted of 15 items (lack of energy, side effects, pain, losing weight, bone pain, fatigue, enjoying life, short of breath, worsened condition, appetite, coughing, bothered by fevers, ability to work, hematuria and sleep). Each of the 15 items was answered on a 5-point Likert scale ranging from 0 to 4 (0= not at all, 1= a little bit, 2= somewhat, 3= quite a bit, 4= very much). Total FKSI score = sum of the 15 item scores; total range: 0 - 60; 0 (no symptoms) to 60 (very much); higher score indicated greater presence of symptoms/worse quality of life.

EQ-5D-3L, a health profile questionnaire was used to assess quality of life along 5 dimensions. Participants rated 5 aspects of health (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) by choosing from 3 answering options (1=no problems; 2=some problems; 3=extreme problems). The mean of the summed score ranged from 1 to 3 with "1" corresponding to no problems and "3" corresponding to severe problems in the 5 dimensions, where higher score indicates more severe problems. Total index EQ-5D-3L summary score is weighted with a range of -0.594 (worst) to 1.0 (best).

EQ-5D-3L, a health profile questionnaire was used to assess quality of life along 5 dimensions. Participants rated 5 aspects of health (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) by choosing from 3 answering options (1=no problems; 2=some problems; 3=extreme problems). The summed score ranged from 1-15 with "1" corresponding to no problems and "15" corresponding to severe problems in the 5 dimensions, where higher score indicates more severe problems.

EQ-5D-3L, a health profile questionnaire was used to assess quality of life along 5 dimensions. Participants rated 5 aspects of health (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) by choosing from 3 answering options (1=no problems; 2=some problems; 3=extreme problems). The summed score ranged from 1-15 with "1" corresponding to no problems and "15" corresponding to severe problems in the 5 dimensions, where higher score indicates more severe problems.

EQ-5D-3L, a health profile questionnaire was used to assess quality of life along 5 dimensions. Participants rated 5 aspects of health (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) by choosing from 3 answering options (1=no problems; 2=some problems; 3=extreme problems). The summed score ranged from 1-15 with "1" corresponding to no problems and "15" corresponding to severe problems in the 5 dimensions, where higher score indicates more severe problems.

EQ-5D-3L, a health profile questionnaire was used to assess quality of life along 5 dimensions. Participants rated 5 aspects of health (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) by choosing from 3 answering options (1=no problems; 2=some problems; 3=extreme problems). The summed score ranged from 1-15 with "1" corresponding to no problems and "15" corresponding to severe problems in the 5 dimensions, where higher score indicates more severe problems.

FKSI-DRS was used to assess quality of life in participants and consisted of 9 items (lack of energy, pain, losing weight, bone pain, fatigue, short of breath, coughing, bothered by fevers, and hematuria). Each of the 9 items was answered on a 5-point Likert scale ranging from 0 to 4 (0= not at all, 1= a little bit, 2= somewhat, 3= quite a bit, 4= very much). Total FKSI-DRS score = sum of the 9 item scores; total range: 0 - 36; 0 (no symptom) to 36 (very much); higher score indicated greater presence of symptom.

FKSI-DRS was used to assess quality of life in participants and consisted of 9 items (lack of energy, pain, losing weight, bone pain, fatigue, short of breath, coughing, bothered by fevers, and hematuria). Each of the 9 items was answered on a 5-point Likert scale ranging from 0 to 4 (0= not at all, 1= a little bit, 2= somewhat, 3= quite a bit, 4= very much). Total FKSI-DRS score = sum of the 9 item scores; total range: 0 - 36; 0 (no symptom) to 36 (very much); higher score indicated greater presence of symptom.

FKSI-DRS was used to assess quality of life in participants and consisted of 9 items (lack of energy, pain, losing weight, bone pain, fatigue, short of breath, coughing, bothered by fevers, and hematuria). Each of the 9 items was answered on a 5-point Likert scale ranging from 0 to 4 (0= not at all, 1= a little bit, 2= somewhat, 3= quite a bit, 4= very much). Total FKSI-DRS score = sum of the 9 item scores; total range: 0 - 36; 0 (no symptom) to 36 (very much); higher score indicated greater presence of symptom.

FKSI-DRS was used to assess quality of life in participants and consisted of 9 items (lack of energy, pain, losing weight, bone pain, fatigue, short of breath, coughing, bothered by fevers, and hematuria). Each of the 9 items was answered on a 5-point Likert scale ranging from 0 to 4 (0= not at all, 1= a little bit, 2= somewhat, 3= quite a bit, 4= very much). Total FKSI-DRS score = sum of the 9 item scores; total range: 0 - 36; 0 (no symptom) to 36 (very much); higher score indicated greater presence of symptom.

FKSI-DRS was used to assess quality of life in participants and consisted of 9 items (lack of energy, pain, losing weight, bone pain, fatigue, short of breath, coughing, bothered by fevers, and hematuria). Each of the 9 items was answered on a 5-point Likert scale ranging from 0 to 4 (0= not at all, 1= a little bit, 2= somewhat, 3= quite a bit, 4= very much). Total FKSI-DRS score = sum of the 9 item scores; total range: 0 - 36; 0 (no symptom) to 36 (very much); higher score indicated greater presence of symptom.

Overall survival was defined as the time from the start of 3rd line treatment until date of death due to any cause.

Overall survival at Year 1 (Month 12) was defined as the time from the start of 3rd line treatment until death or 1 year due to any cause (measured at the end of 12 month follow-up/observation period). Percentage of participants who survived at the completion of 1 year (12 months) period were reported in this outcome measure.

Time to treatment failure was defined as the time from the start of treatment to the date of disease progression or date of permanent discontinuation. PD as per RECIST version 1.1 was defined as at least a 20% increase in the sum of longest dimensions of target lesions, reference to the smallest sum of the longest dimensions recorded since the treatment started, or the appearance of one or more new lesions or increase of at least 5 mm in addition to the relative increase of 20%.

An AE was any untoward medical occurrence in a participant who received disease treatment without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant and jeopardized the participants or required treatment to prevent other AE outcomes for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment emergent AEs were events which occurred between start of disease treatment and up to Month 12 follow-up visit, that were absent before treatment or that worsened relative to pre-treatment state. AEs included both non-SAE and SAEs.

An AE was any untoward medical occurrence in a participant who received disease treatment without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant and jeopardized the participants or required treatment to prevent other AE outcomes for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. AEs were graded according to the National Cancer Institute- Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03 and coded using the Medical Dictionary for Regulatory Activities (MedDRA) as Grade 1: Mild, Grade 2: Moderate, Grade 3: Severe, Grade 4: Life threatening, Grade 5: Death related to AE. AEs included both SAEs and non-SAEs.

An AE was any untoward medical occurrence in a participant who received disease treatment without regard to possibility of causal relationship. Treatment emergent AEs during third line targeted treatment were events which occurred between first dose of third line targeted treatment and up to Month 12 follow-up visit, that were absent before treatment or that worsened relative to pre-treatment state.

Number of participants that required dose modifications of third line treatment due to AEs were reported in this outcome measure. Dose modification was categorized as escalation (increase in dose), delay or interruptions (change in dose time or skipping any dose), reduction (decrease in dose).