Study of Patients With Metastatic and/or Advanced Renal Cell Carcinoma, Treated With Sunitinib/Axitinib.

• Sponsor: Pfizer (Industry)
• Overall Status: Completed
• CT.gov ID: NCT04033991
• Collaborator: (none)
• Enrollment: 684
• Location: 1
• Actual Duration (Months): 14.7
• Patients Per Site Per Month: 46.5

Study Details

Study Description

Brief Summary

Research Questions:

To understand the clinical outcomes of patients treated with sunitinib in first line and axitinib in second line in a real world setting as therapies for metastatic and/or advanced renal cell carcinoma (mRCC).

Primary Objective:

1. What is the progression free survival (PFS) of patients treated in first line with sunitinib, and stratified by Memorial Sloan-Kettering Cancer Center / International Metastatic Renal Cell Carcinoma Database Consortium (MSKCC/IMDC) risk category (favourable, intermediate, poor)?

2. What is the progression free survival (PFS) of patients treated in second line with axitinib, and stratified by MSKCC/IMDC risk category (favourable, intermediate, poor)?

Condition or Disease	Intervention/Treatment	Phase
Carcinoma; Renal Cell	Drug: Sunitinib; Drug: Axitinib

Detailed Description

Research Questions:

To understand the clinical outcomes of patients treated with sunitinib in first line and axitinib in second line in a real world setting as therapies for metastatic and/or advanced renal cell carcinoma (mRCC).

Primary Objective:

1. What is the progression free survival (PFS) of patients treated in first line with sunitinib, and stratified by Memorial Sloan-Kettering Cancer Center / International Metastatic Renal Cell Carcinoma Database Consortium (MSKCC/IMDC) risk category (favourable, intermediate, poor)?

2. What is the progression free survival (PFS) of patients treated in second line with axitinib, and stratified by MSKCC/IMDC risk category (favourable, intermediate, poor)?

Secondary Objectives:

First Line:

1. What is the overall survival (OS) of all patients in first line with sunitinib, and stratified by MSKCC risk (favourable, intermediate, poor)?

2. What is the duration of therapy with sunitinib in first line (using time to treatment discontinuation [TTD]) for all patients and stratified by MSKCC risk (favourable, intermediate, poor)

3. Objective response rate (ORR)

4. Duration of objective response (complete response [CR] or partial response [PR])

5. Examine factors that predict TTD, e.g. risk stratification, or individual/grouped parameters that comprise the prognostic classification systems

6. Less than one year from time of diagnosis

7. Karnovsky performance status less than 80%

8. Haemoglobin less than the lower limit of normal (e.g. less than 12 g/dl)

9. Serum calcium great than the upper limit of normal (e.g. 10 mg/dl or : 2.5 mmol/l)

10. Neutrophil greater than the upper limit of normal (e.g. greater than 7.0 x109 dl)

11. Platelets greater than the upper limit of normal (e.g. greater than 400 000)

12. Lactate dehydrogenase greater than 1.5 times the upper limit of normal

13. Fuhrmann grade of tumour

14. Tumour subtype e.g. clear cell versus. non-clear cell

15. Safety and tolerability data reporting for first line sunitinib

Second line:

1. What is the OS of all patients in second line with axitinib, and stratified by MSKCC risk (favourable, intermediate, poor)?

2. What is the duration of therapy with axitinib in second line (using TTD) for all patients and stratified by MSKCC risk (favourable, intermediate, poor)

3. ORR

4. Duration of objective response (CR or PR)

5. Examine factors that predict duration of TTD, e.g. risk stratification, or individual/grouped parameters that comprise the prognostic classification systems

6. Less than one year from time of diagnosis

7. Karnovsky performance status less than 80%

8. Haemoglobin less than the lower limit of normal (e.g. less than 12 g/dl)

9. Serum calcium great than the upper limit of normal (e.g. 10 mg/dl or : 2.5 mmol/l)

10. Neutrophil greater than the upper limit of normal (e.g. greater than 7.0 x109 dl)

11. Platelets greater than the upper limit of normal (e.g. greater than 400 000)

12. Lactate dehydrogenase greater than 1.5 times the upper limit of normal

13. Fuhrmann grade of tumour

14. Tumour subtype e.g. clear cell vs. non-clear cell

15. Safety and tolerability reporting for second line axitinib

The objectives listed below will also be assessed as exploratory analyses for various patient subgroups of interest, and will be conducted if sufficient numbers of patients are available:

1. Axitinib PFS and OS, as a second line therapy following sunitinib, pazopanib, or following other Tyrosine kinase inhibitors (e.g. sorafenib)

2. Axitinib PFS and OS as a third line therapy

3. Axitinib PFS and OS post-immunotherapy (IO), taking into consideration 2nd and 3rd therapy lines, following all IO therapy options, E.g. atezolizumab/bevacizumab, nivolumab/ipilumimab, nivolumab, interleukin-2

4. For the post-sunitinib axitinib cohort: What was the duration of sunitinib therapy before patients transitioned to axitinib?

5. For the post-pazopanib axitinib cohort: What was the duration of sunitinib therapy before patients transitioned to axitinib?

6. Is the duration of therapy on first line sunitinib and/or pazopanib related to duration of therapy for second line axitinib?

Study Design

• Study Type: Observational
• Actual Enrollment: 684 participants
• Observational Model: Cohort
• Time Perspective: Retrospective
• Official Title: A Real World Retrospective Database Study of Patients Diagnosed With Metastatic and/or Advanced Renal Cell Carcinoma and Treated With Sunitinib and/or Axitinib in a Specialist United Kingdom Oncology Centre
• Actual Study Start Date: Sep 27, 2019
• Actual Primary Completion Date: Dec 18, 2020
• Actual Study Completion Date: Dec 18, 2020

Arms and Interventions

Arm	Intervention/Treatment
Patients with advanced RCC Patients with a diagnosis of kidney cancer (renal cell carcinoma, advanced or metastatic)	Drug: Sunitinib; Tyrosine kinase inhibitor, licensed for use in treatment of renal cell carcinoma.; Other Names: Sutent ; Drug: Axitinib; Tyrosine kinase inhibitor, licensed for use in treatment of renal cell carcinoma.; Other Names: Inlyta

Outcome Measures

Primary Outcome Measures

1. Progression Free Survival (PFS) [From start of treatment to PD, death or end of treatment, whichever occurred first, from inception of database (2002) until 30 June 2018, anytime in these 16 years (from the data retrieved and observed retrospectively for approximately 1.2 years)]

   PFS was duration measured from the first date of each treatment line to the date of disease progression (PD), end of treatment date or date of death. Participants who were on treatment were censored on 30 June 2018. If a participant stopped due to toxicity, the earliest date from the date of progression or end of treatment date was assigned. PD per Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1 was defined as at least a 20 percent (%) increase in sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to 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 progression.

2. Progression Free Survival (PFS): Memorial Sloan-Kettering Cancer Center (MSKCC) Stratification [From start of treatment to PD, death or end of treatment, whichever occurred first, from inception of database (2002) until 30 June 2018, anytime in these 16 years (from the data retrieved and observed retrospectively for approximately 1.2 years)]

   PFS: first date of each treatment line to the date of PD, end of treatment date or date of death. Participants who were on treatment were censored on 30 June 2018. If a participant stopped due to toxicity, the earliest date from date of PD or end of treatment date was assigned. MSKCC criteria had 5 risk factors: Karnofsky performance status (KPS) <80% (ability to perform ordinary tasks, 0 [dead] -100 [normal]); time from diagnosis to start of systemic therapy <12 months; hemoglobin <lower limit of normal (LLN); lactate dehydrogenase 1.5*upper limit of normal (ULN); corrected serum calcium >10 milligram per deciliter (mg/dL). Present risk factors were added, and participants were stratified as: favorable (0 factor), intermediate (1-2 factors), poor (>=3 factors). PD: >=20% increase in sum of diameters of target lesions, taking as reference smallest sum on study, the sum must also demonstrate an absolute increase of at least 5 mm. Appearance of 1 or more new lesions was considered PD.

3. Progression Free Survival (PFS): International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) Stratification [From start of treatment to PD, death or end of treatment, whichever occurred first, from inception of database (2002) until 30 June 2018, anytime in these 16 years (from the data retrieved and observed retrospectively for approximately 1.2 years)]

   PFS: duration measured from first date of each treatment line to the date of PD, end of treatment date or date of death. Participants who were on treatment were censored on 30 June 2018. If a participant stopped due to toxicity, the earliest date from date of PD or end of treatment date was assigned. IMDC criteria had 6 risk factors: KPS <80% (ability to perform ordinary tasks, 0 [dead] -100 [normal]); time from diagnosis to start of systemic therapy <12 months; corrected serum calcium >10 mg/dL; neutrophils and platelets >LLN; hemoglobin <LLN. Present risk factors were added, and then participants were stratified as: favorable (0 factor), intermediate (1-2 factors), poor (>=3 factors). PD: >=20% increase in sum of diameters of target lesions, taking as reference smallest sum on study, the sum must also demonstrate an absolute increase of at least 5 mm. Appearance of 1 or more new lesions was also considered PD.

Secondary Outcome Measures

1. Overall Survival (OS) [From index date until death, from inception of database (2002) until 30 June 2018, anytime in these 16 years (from the data retrieved and observed retrospectively for approximately 1.2 years)]

   OS was defined as the time between the index date and the date of death from any cause. Participants who were still alive at the study end date or the last visit date available were censored. Index date: date of initiation of first-line sunitinib therapy and second-line axitinib therapy.

2. Overall Survival (OS): Memorial Sloan-Kettering Cancer Center (MSKCC) Stratification [From index date until death, from inception of database (2002) until 30 June 2018, anytime in these 16 years (from the data retrieved and observed retrospectively for approximately 1.2 years)]

   OS was defined as the time between the index date and the date of death from any cause. Participants who were still alive at the study end date or the last visit date available were censored. MSKCC criteria had 5 risk factors: KPS <80% (ability to perform ordinary tasks, 0 [dead] -100 [normal]); time from diagnosis to start of systemic therapy <12 months; hemoglobin <LLN; lactate dehydrogenase 1.5* ULN; corrected serum calcium >10.0 mg/dL. Present risk factors were added, and then participants were stratified in following prognosis group: favorable (0 factor), intermediate (1-2 factors), poor (>=3 factors), unknown/missing = no information available. Index date: date of initiation of first-line sunitinib therapy and second-line axitinib therapy.

3. Overall Survival (OS): International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) Stratification [From index date until death, from inception of database (2002) until 30 June 2018, anytime in these 16 years (from the data retrieved and observed retrospectively for approximately 1.2 years)]

   OS was defined as the time between the index date and the date of death from any cause. Participants who were still alive at the study end date or the last visit date available were censored. IMDC criteria had 6 risk factors: KPS <80% (ability to perform ordinary tasks, 0 [dead] -100 [normal]); time from diagnosis to start of systemic therapy <12 months; corrected serum calcium >10.0 mg/dL; neutrophils and platelets >LLN and hemoglobin <LLN. Present risk factors were added, and then participants were stratified in following prognosis group: favorable (0 factor), intermediate (1-2 factors), poor (>=3 factors), unknown/missing =no information available. Index date: date of initiation of first-line sunitinib therapy and second-line axitinib therapy.

4. Number of Participants With Best Overall Response (BOR) for Complete Response (CR), Partial Response (PR), Stable Disease (SD), PD and Surgical CR as Per RECIST v 1.1 [Start of treatment till BOR of CR, PR, PD, SD, Surgical CR, or death/initiation of new therapy, whichever occurred first; from 2002 to 30 June 2018, anytime in these 16 years (data retrieved and observed retrospectively for approximately 1.2 years)]

   BOR was recorded for CR, PR, SD, PD and surgical CR. RECIST v1.1, a) CR: disappearance of target, non-target lesions and normalization of tumor markers. Pathological lymph nodes had short axis measures <10mm; b) PR: >=30% decrease in sum of measures (longest diameter for tumor lesions, short axis measure for nodes) of target lesions, taking reference baseline sum of diameters. Non-target lesions must be non-PD; c) PD: >=20% increase in sum of diameters of target lesions, taking as reference smallest sum on study, sum must demonstrate absolute increase of at least 5mm. Appearance of 1 or more new lesions; d) SD: neither shrinkage for CR/PR nor increase for PD taking as reference smallest sum of longest diameters since treatment start; e) Surgical CR: disappearance of target, non-target lesions, normalization of tumor markers, pathological lymph nodes had short axis measuring <10mm as result of surgery. Alive participants with no events were censored at final study cutoff date.

5. Objective Response Rate (ORR) [From start of treatment until CR,PR,PD,death/initiation of new therapy, whichever occurred first, from inception of database(2002) until 30 June 2018, anytime in these 16 years (from data retrieved and observed retrospectively for approximately 1.2 years)]

   ORR was defined as the percentage of participants who achieved a BOR of CR or PR as per RECIST v1.1. CR was defined as disappearance of target and non-target lesions and normalization of tumor markers. Pathological lymph nodes must have short axis measures <10 mm. PR was defined as at least a 30% decrease in the sum of measures (longest diameter for tumor lesions and short axis measure for nodes) of target lesions, taking as reference baseline sum of diameters. Non-target lesions must be non-PD. PD was defined as at least a 20% increase in sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to 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 considered progression. Alive participants who did not have event were censored at final study cutoff date.

6. Duration of Response (DOR) [From date of first documented CR/PR until PD/death/initiation of new therapy, whichever occurred first, from inception of database(2002) until 30 June 2018, anytime in these 16years (data retrieved and observed retrospectively for approximately 1.2 years)]

   DOR was defined as the time between the date of the first documented confirmed response (PR or CR) and the date of the first documented progression or death due to any cause. Alive participants who did not have event were censored at final study cutoff date. As per RECIST v1.1: CR was defined as disappearance of target and non-target lesions and normalization of tumor markers. Pathological lymph nodes short axis measures <10 mm. PR was defined as at least 30% decrease in sum of measures (tumor lesions- longest diameter and nodes- short axis) of target lesions, taking as reference baseline sum of diameters. PD was defined as at least 20% increase in sum of diameters of measured lesions taking as references smallest sum of diameters recorded on study (including baseline) and an absolute increase of >=5 mm or appearance of at least 1 new lesion.

7. Time to Treatment Discontinuation (TTD) [From start of the treatment until end of treatment, from inception of database (2002) until 30 June 2018, anytime in these 16 years (from the data retrieved and observed retrospectively for approximately 1.2 years)]

   TTD was defined as the time between initiation of treatment to the end of treatment for any reason including PD, death, and lost-to follow up. Participants were censored on the study end date or at last office visit date without clinical or radiographic evidence of PD, whichever occurred first.

8. Time to Treatment Discontinuation (TTD): Memorial Sloan-Kettering Cancer Center (MSKCC) Stratification [From start of the treatment until end of treatment, from inception of database (2002) until 30 June 2018, anytime in these 16 years (from the data retrieved and observed retrospectively for approximately 1.2 years)]

   TTD was defined as the time between initiation of treatment to the end of treatment for any reason including PD, death, and lost-to follow up. Participants were censored on the study end date or at last office visit date without clinical or radiographic evidence of PD, whichever occurred first. MSKCC criteria had following 5 risk factors: KPS <80% (ability to perform ordinary tasks, 0 [dead] -100 [normal]); time from diagnosis to start of systemic therapy <12 months; hemoglobin <LLN; lactate dehydrogenase 1.5*ULN; corrected serum calcium >10.0 mg/dL. Present risk factors were added, and then participants were stratified in following prognosis group: favorable (0 factor), intermediate (1-2 factors), poor (>=3 factors), unknown/missing = no information available.

9. Time to Treatment Discontinuation (TTD): International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) Stratification [From start of the treatment until end of treatment, from inception of database (2002) until 30 June 2018, anytime in these 16 years (from the data retrieved and observed retrospectively for approximately 1.2 years)]

   TTD was defined as the time between initiation of treatment to the end of treatment for any reason including PD, death, and lost-to follow up. Participants were censored on the study end date or at last office visit date without clinical or radiographic evidence of PD, whichever occurred first. IMDC criteria had following 6 risk factors: KPS <80% (ability to perform ordinary tasks, 0 [dead] -100 [normal]); time from diagnosis to start of systemic therapy <12 months; corrected serum calcium >10.0 mg/dL; neutrophils and platelets >LLN and hemoglobin <LLN. Present risk factors were added, and then participants were stratified in following prognosis group: favorable (0 factor), intermediate (1-2 factors), poor (>=3 factors), unknown/missing =no information available.

10. Durable Response Rate (DRR) [6 months from inception of database (2002) until 30 June 2018, anytime in these 16 years (from the data retrieved and observed retrospectively for approximately 1.2 years)]

    DRR was determined as the percentage of participants with objective response (CR or PR) with a duration of at least 6 months. As per RECIST v1.1: CR was defined as disappearance of target and non-target lesions and normalization of tumor markers. Pathological lymph nodes short axis measures <10 mm. PR was defined as at least 30% decrease in sum of measures (tumor lesions- longest diameter and nodes- short axis) of target lesions, taking as reference baseline sum of diameters.

Other Outcome Measures

1. Number of Participants Who Started Systemic Therapy Within 1 Year of Diagnosis [Baseline (data retrieved and observed retrospectively for approximately 1.2 years)]

2. Number of Participants With Karnofsky Performance Status (KPS) Less Than 80 Percent (%) [Baseline (data retrieved and observed retrospectively for approximately 1.2 years)]

   KPS: used for rating participant activities of daily living on scale from 0-100, higher score = participant is better able to carry out daily activities. Score range: 100 = normal no complaints; no disease evidence, 90 = able to carry normal activity; minor signs/symptoms of disease, 80 = normal activity with effort; some signs/symptoms, 70 = cares for self; unable to carry on normal activity, 60 = requires occasional assistance, but able to care for most personal needs, 50 = requires considerable assistance and frequent medical care, 40 = disabled; requires special care, assistance, 30 = severely disabled; hospital admission is indicated although death not imminent, 20 = very sick; hospital admission necessary, 10 = moribund; fatal processes progressing rapidly and 0 = dead. The lower the score the worse is survival for most serious illnesses. Here, number of participants with KPS <80% were reported.

3. Number of Participants With Hemoglobin Less Than Lower Limit of Normal (LLN) [Baseline (data retrieved and observed retrospectively for approximately 1.2 years)]

   In this outcome measure number of participants with hemoglobin less than LLN were reported. For male participants LLN was 130 grams per liter and for female participants LLN was 115 grams per liter.

4. Number of Participants With Serum Calcium >Upper Limit of Normal (ULN), Neutrophil >ULN, Platelets >ULN and Lactate Dehydrogenase >1.5*ULN [Baseline (data retrieved and observed retrospectively for approximately 1.2 years)]

   Number of participants with serum calcium >ULN (3.00 millimole per liter [mmol/L]), neutrophils >ULN (7.5 *10^9/L), platelets >ULN (400 *10^9/L), lactate dehydrogenase >1.5*ULN were reported in this outcome measure.

5. Number of Participants Per Tumor Fuhrman Grades [Baseline (data retrieved and observed retrospectively for approximately 1.2 years)]

   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.

6. Number of Participants With Tumor Subtype [Baseline (data retrieved and observed retrospectively for approximately 1.2 years)]

   In this outcome measure, number of participants were classified according to tumor subtype as clear cell, non-clear cell and unknown/missing.

7. Number of Participants With Adverse Events [From start of treatment until death, from inception of database (2002) until 30 June 2018, anytime in these 16 years (from the data retrieved and observed retrospectively for approximately 1.2 years)]

   An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship with the study treatment.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion criteria

1. Over the age of 18 years

2. Diagnosis of renal cell carcinoma

3. Treatment with sunitinib and/or axitinib

4. Timeframe: from database inception date (2002) until June 30, 2018.

Exclusion criteria

Patients meeting any of the following criteria will not be included in the study:

1. Under the age of 18 years

2. Diagnosis other than renal cell carcinoma

3. No treatment with sunitinib and/or axitinib

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Pfizer UK	London		United Kingdom

Sponsors and Collaborators

• Pfizer

Investigators

• Study Director: Pfizer CT.gov Call Center, Pfizer

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Aug 14, 2019

More Information

Additional Information:

• To obtain contact information for a study center near you, click here.

Publications

None provided.

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT04033991
• Other Study ID Numbers: X9001180
• First Posted: Jul 26, 2019
• Last Update Posted: Feb 18, 2022
• Last Verified: Dec 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Keywords provided by Pfizer: Carcinoma;; renal cell;; cancer;; kidney;; sunitinib;; axitinib
• Additional relevant MeSH terms: Carcinoma; Carcinoma, Renal Cell; Sunitinib; Axitinib

Study Results

Participant Flow

Recruitment Details

Data of participants treated with first-line sunitinib and/or second-line axitinib in real world settings for metastatic renal cell carcinoma (mRCC) and/or advanced renal cell carcinoma (aRCC), from 2002 until 30 June 2018, were retrieved from Christie National Health Service (NHS) database. Available data were extracted, curated and analyzed during approximately 1.2 years of this retrospective, observational study.

Arm/Group Title	Participants With mRCC and/or aRCC
Arm/Group Description	Participants who met the selection criteria, diagnosed with mRCC and/or aRCC, received sunitinib as first-line treatment and/or axitinib as second-line treatment from 2002 till 30 June 2018, according to normal routine healthcare practice in real-world setting, were included in this study. Data of these participants were derived from Christie NHS database.
Period Title: Overall Study
STARTED	684
Participants Who Took First-line Sunitinib Therapy	622
Participants Who Took Second-line Axitinib Therapy	121
Participants Who Took First-line Sunitinib Therapy and Then Second-line Axitinib Therapy	59
Participants Who Took Drugs Other Than Sunitinib as First-line and Then Second-line Axitinib Therapy	62
COMPLETED	684
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Participants With mRCC and/or aRCC
Arm/Group Description	Participants who met the selection criteria, diagnosed with mRCC and/or aRCC, received sunitinib as first-line treatment and/or axitinib as second-line treatment from 2002 till 30 June 2018, according to normal routine healthcare practice in real-world setting, were included in this study. Data of these participants were derived from Christie NHS database.
Overall Participants	684
Age, Customized (Count of Participants)
Less than (<) 65 years	301 44%
Greater than or equal to (>=) 65 to <75 years	247 36.1%
>=75 to <84 years	124 18.1%
Greater than or equal to (>=) 85 years	12 1.8%
Sex: Female, Male (Count of Participants)
Female	234 34.2%
Male	450 65.8%
Race and Ethnicity Not Collected (Count of Participants)

Outcome Measures

1. Primary Outcome

Title	Progression Free Survival (PFS)
Description	PFS was duration measured from the first date of each treatment line to the date of disease progression (PD), end of treatment date or date of death. Participants who were on treatment were censored on 30 June 2018. If a participant stopped due to toxicity, the earliest date from the date of progression or end of treatment date was assigned. PD per Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1 was defined as at least a 20 percent (%) increase in sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to 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 progression.
Time Frame	From start of treatment to PD, death or end of treatment, whichever occurred first, from inception of database (2002) until 30 June 2018, anytime in these 16 years (from the data retrieved and observed retrospectively for approximately 1.2 years)

Outcome Measure Data

Analysis Population Description

Analysis population included all eligible participants with mRCC and/or aRCC, received sunitinib as first-line treatment and/or axitinib as second-line treatment from 2002 till 30 June 2018.

Arm/Group Title	Participants With mRCC and/or aRCC: First Line Sunitinib Treatment	Participants With mRCC and/or aRCC: Second Line Axitinib Treatment
Arm/Group Description	Participants who met the selection criteria, diagnosed with mRCC and/or aRCC, received sunitinib as first-line treatment from 2002 till 30 June 2018, according to normal routine healthcare practice in real-world setting, were included in this reporting arm. Data of these participants were derived from Christie NHS database.	Participants who met the selection criteria, diagnosed with mRCC and/or aRCC, received axitinib as second-line treatment from 2002 till 30 June 2018, according to normal routine healthcare practice in real-world setting, were included in this reporting arm. Data of these participants were derived from Christie NHS database.
Measure Participants	622	121
Median (95% Confidence Interval) [Months]	8.394	6.177

2. Primary Outcome

Title	Progression Free Survival (PFS): Memorial Sloan-Kettering Cancer Center (MSKCC) Stratification
Description	PFS: first date of each treatment line to the date of PD, end of treatment date or date of death. Participants who were on treatment were censored on 30 June 2018. If a participant stopped due to toxicity, the earliest date from date of PD or end of treatment date was assigned. MSKCC criteria had 5 risk factors: Karnofsky performance status (KPS) <80% (ability to perform ordinary tasks, 0 [dead] -100 [normal]); time from diagnosis to start of systemic therapy <12 months; hemoglobin <lower limit of normal (LLN); lactate dehydrogenase 1.5*upper limit of normal (ULN); corrected serum calcium >10 milligram per deciliter (mg/dL). Present risk factors were added, and participants were stratified as: favorable (0 factor), intermediate (1-2 factors), poor (>=3 factors). PD: >=20% increase in sum of diameters of target lesions, taking as reference smallest sum on study, the sum must also demonstrate an absolute increase of at least 5 mm. Appearance of 1 or more new lesions was considered PD.
Time Frame	From start of treatment to PD, death or end of treatment, whichever occurred first, from inception of database (2002) until 30 June 2018, anytime in these 16 years (from the data retrieved and observed retrospectively for approximately 1.2 years)

Outcome Measure Data

Analysis Population Description

Analysis population included all eligible participants with mRCC and/or aRCC, received sunitinib as first-line treatment and/or axitinib as second-line treatment from 2002 till 30 June 2018. Here "Number Analyzed" signifies number of participants evaluable for specified rows.

Arm/Group Title	Participants With mRCC and/or aRCC: First Line Sunitinib Treatment	Participants With mRCC and/or aRCC: Second Line Axitinib Treatment
Arm/Group Description	Participants who met the selection criteria, diagnosed with mRCC and/or aRCC, received sunitinib as first-line treatment from 2002 till 30 June 2018, according to normal routine healthcare practice in real-world setting, were included in this reporting arm. Data of these participants were derived from Christie NHS database.	Participants who met the selection criteria, diagnosed with mRCC and/or aRCC, received axitinib as second-line treatment from 2002 till 30 June 2018, according to normal routine healthcare practice in real-world setting, were included in this reporting arm. Data of these participants were derived from Christie NHS database.
Measure Participants	622	121
Favorable	14.784	12.649
Intermediate	8.986	8.903
Poor	2.628	1.610
Unknown/missing (no information available)	NA	NA

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Participants With mRCC and/or aRCC: First Line Sunitinib Treatment
	Comments	Data were compared statistically across all 3 categories (favorable, intermediate and poor).
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Log Rank
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Participants With mRCC and/or aRCC: Second Line Axitinib Treatment
	Comments	Data were compared statistically across all 3 categories (favorable, intermediate and poor).
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Log Rank
	Comments

3. Primary Outcome

Title	Progression Free Survival (PFS): International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) Stratification
Description	PFS: duration measured from first date of each treatment line to the date of PD, end of treatment date or date of death. Participants who were on treatment were censored on 30 June 2018. If a participant stopped due to toxicity, the earliest date from date of PD or end of treatment date was assigned. IMDC criteria had 6 risk factors: KPS <80% (ability to perform ordinary tasks, 0 [dead] -100 [normal]); time from diagnosis to start of systemic therapy <12 months; corrected serum calcium >10 mg/dL; neutrophils and platelets >LLN; hemoglobin <LLN. Present risk factors were added, and then participants were stratified as: favorable (0 factor), intermediate (1-2 factors), poor (>=3 factors). PD: >=20% increase in sum of diameters of target lesions, taking as reference smallest sum on study, the sum must also demonstrate an absolute increase of at least 5 mm. Appearance of 1 or more new lesions was also considered PD.
Time Frame	From start of treatment to PD, death or end of treatment, whichever occurred first, from inception of database (2002) until 30 June 2018, anytime in these 16 years (from the data retrieved and observed retrospectively for approximately 1.2 years)

Outcome Measure Data

Analysis Population Description

Analysis population included all eligible participants with mRCC and/or aRCC, received sunitinib as first-line treatment and/or axitinib as second-line treatment from 2002 till 30 June 2018. Here "Number Analyzed" signifies number of participants evaluable for specified rows.

Arm/Group Title	Participants With mRCC and/or aRCC: First Line Sunitinib Treatment	Participants With mRCC and/or aRCC: Second Line Axitinib Treatment
Arm/Group Description	Participants who met the selection criteria, diagnosed with mRCC and/or aRCC, received sunitinib as first-line treatment from 2002 till 30 June 2018, according to normal routine healthcare practice in real-world setting, were included in this reporting arm. Data of these participants were derived from Christie NHS database.	Participants who met the selection criteria, diagnosed with mRCC and/or aRCC, received axitinib as second-line treatment from 2002 till 30 June 2018, according to normal routine healthcare practice in real-world setting, were included in this reporting arm. Data of these participants were derived from Christie NHS database.
Measure Participants	622	121
Favorable	13.979	12.649
Intermediate	9.955	7.162
Poor	5.569	2.990
Unknown/missing (no information available)	NA	NA

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Participants With mRCC and/or aRCC: First Line Sunitinib Treatment
	Comments	Data were compared statistically across all 3 categories (favorable, intermediate and poor).
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Log Rank
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Participants With mRCC and/or aRCC: Second Line Axitinib Treatment
	Comments	Data were compared statistically across all 3 categories (favorable, intermediate and poor).
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0068
	Comments
	Method	Log Rank
	Comments

4. Secondary Outcome

Title	Overall Survival (OS)
Description	OS was defined as the time between the index date and the date of death from any cause. Participants who were still alive at the study end date or the last visit date available were censored. Index date: date of initiation of first-line sunitinib therapy and second-line axitinib therapy.
Time Frame	From index date until death, from inception of database (2002) until 30 June 2018, anytime in these 16 years (from the data retrieved and observed retrospectively for approximately 1.2 years)

Outcome Measure Data

Analysis Population Description

Analysis population included all eligible participants with mRCC and/or aRCC, received sunitinib as first-line treatment and/or axitinib as second-line treatment from 2002 till 30 June 2018.

Arm/Group Title	Participants With mRCC and/or aRCC: First Line Sunitinib Treatment	Participants With mRCC and/or aRCC: Second Line Axitinib Treatment
Arm/Group Description	Participants who met the selection criteria, diagnosed with mRCC and/or aRCC, received sunitinib as first-line treatment from 2002 till 30 June 2018, according to normal routine healthcare practice in real-world setting, were included in this reporting arm. Data of these participants were derived from Christie NHS database.	Participants who met the selection criteria, diagnosed with mRCC and/or aRCC, received axitinib as second-line treatment from 2002 till 30 June 2018, according to normal routine healthcare practice in real-world setting, were included in this reporting arm. Data of these participants were derived from Christie NHS database.
Measure Participants	622	121
Median (95% Confidence Interval) [Months]	18.333	15.836

5. Secondary Outcome

Title	Overall Survival (OS): Memorial Sloan-Kettering Cancer Center (MSKCC) Stratification
Description	OS was defined as the time between the index date and the date of death from any cause. Participants who were still alive at the study end date or the last visit date available were censored. MSKCC criteria had 5 risk factors: KPS <80% (ability to perform ordinary tasks, 0 [dead] -100 [normal]); time from diagnosis to start of systemic therapy <12 months; hemoglobin <LLN; lactate dehydrogenase 1.5* ULN; corrected serum calcium >10.0 mg/dL. Present risk factors were added, and then participants were stratified in following prognosis group: favorable (0 factor), intermediate (1-2 factors), poor (>=3 factors), unknown/missing = no information available. Index date: date of initiation of first-line sunitinib therapy and second-line axitinib therapy.
Time Frame	From index date until death, from inception of database (2002) until 30 June 2018, anytime in these 16 years (from the data retrieved and observed retrospectively for approximately 1.2 years)

Outcome Measure Data

Analysis Population Description

Analysis population included all eligible participants with mRCC and/or aRCC, received sunitinib as first-line treatment and/or axitinib as second-line treatment from 2002 till 30 June 2018. Here, "Number Analyzed" signifies number of participants evaluable for specified rows.

Arm/Group Title	Participants With mRCC and/or aRCC: First Line Sunitinib Treatment	Participants With mRCC and/or aRCC: Second Line Axitinib Treatment
Arm/Group Description	Participants who met the selection criteria, diagnosed with mRCC and/or aRCC, received sunitinib as first-line treatment from 2002 till 30 June 2018, according to normal routine healthcare practice in real-world setting, were included in this reporting arm. Data of these participants were derived from Christie NHS database.	Participants who met the selection criteria, diagnosed with mRCC and/or aRCC, received axitinib as second-line treatment from 2002 till 30 June 2018, according to normal routine healthcare practice in real-world setting, were included in this reporting arm. Data of these participants were derived from Christie NHS database.
Measure Participants	622	121
Favorable	40.246	NA
Intermediate	18.497	16.164
Poor	5.322	2.694
Unknown/missing (no information available)	NA	NA

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Participants With mRCC and/or aRCC: First Line Sunitinib Treatment
	Comments	Data were compared statistically across all 3 categories (favorable, intermediate and poor).
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Log Rank
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Participants With mRCC and/or aRCC: Second Line Axitinib Treatment
	Comments	Data were compared statistically across all 3 categories (favorable, intermediate and poor).
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0004
	Comments
	Method	Log Rank
	Comments

6. Secondary Outcome

Title	Overall Survival (OS): International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) Stratification
Description	OS was defined as the time between the index date and the date of death from any cause. Participants who were still alive at the study end date or the last visit date available were censored. IMDC criteria had 6 risk factors: KPS <80% (ability to perform ordinary tasks, 0 [dead] -100 [normal]); time from diagnosis to start of systemic therapy <12 months; corrected serum calcium >10.0 mg/dL; neutrophils and platelets >LLN and hemoglobin <LLN. Present risk factors were added, and then participants were stratified in following prognosis group: favorable (0 factor), intermediate (1-2 factors), poor (>=3 factors), unknown/missing =no information available. Index date: date of initiation of first-line sunitinib therapy and second-line axitinib therapy.
Time Frame	From index date until death, from inception of database (2002) until 30 June 2018, anytime in these 16 years (from the data retrieved and observed retrospectively for approximately 1.2 years)

Outcome Measure Data

Analysis Population Description

Analysis population included all eligible participants with mRCC and/or aRCC, received sunitinib as first-line treatment and/or axitinib as second-line treatment from 2002 till 30 June 2018. Here, "Number Analyzed" signifies number of participants evaluable for specified rows.

Arm/Group Title	Participants With mRCC and/or aRCC: First Line Sunitinib Treatment	Participants With mRCC and/or aRCC: Second Line Axitinib Treatment
Arm/Group Description	Participants who met the selection criteria, diagnosed with mRCC and/or aRCC, received sunitinib as first-line treatment from 2002 till 30 June 2018, according to normal routine healthcare practice in real-world setting, were included in this reporting arm. Data of these participants were derived from Christie NHS database.	Participants who met the selection criteria, diagnosed with mRCC and/or aRCC, received axitinib as second-line treatment from 2002 till 30 June 2018, according to normal routine healthcare practice in real-world setting, were included in this reporting arm. Data of these participants were derived from Christie NHS database.
Measure Participants	622	121
Favorable	34.103	NA
Intermediate	20.435	16.394
Poor	9.347	8.049
Unknown/missing (no information available)	NA	NA

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Participants With mRCC and/or aRCC: First Line Sunitinib Treatment
	Comments	Data were compared statistically across all 3 categories (favorable, intermediate and poor).
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Log Rank
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Participants With mRCC and/or aRCC: Second Line Axitinib Treatment
	Comments	Data were compared statistically across all 3 categories (favorable, intermediate and poor).
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0014
	Comments
	Method	Log Rank
	Comments

7. Secondary Outcome

Title	Number of Participants With Best Overall Response (BOR) for Complete Response (CR), Partial Response (PR), Stable Disease (SD), PD and Surgical CR as Per RECIST v 1.1
Description	BOR was recorded for CR, PR, SD, PD and surgical CR. RECIST v1.1, a) CR: disappearance of target, non-target lesions and normalization of tumor markers. Pathological lymph nodes had short axis measures <10mm; b) PR: >=30% decrease in sum of measures (longest diameter for tumor lesions, short axis measure for nodes) of target lesions, taking reference baseline sum of diameters. Non-target lesions must be non-PD; c) PD: >=20% increase in sum of diameters of target lesions, taking as reference smallest sum on study, sum must demonstrate absolute increase of at least 5mm. Appearance of 1 or more new lesions; d) SD: neither shrinkage for CR/PR nor increase for PD taking as reference smallest sum of longest diameters since treatment start; e) Surgical CR: disappearance of target, non-target lesions, normalization of tumor markers, pathological lymph nodes had short axis measuring <10mm as result of surgery. Alive participants with no events were censored at final study cutoff date.
Time Frame	Start of treatment till BOR of CR, PR, PD, SD, Surgical CR, or death/initiation of new therapy, whichever occurred first; from 2002 to 30 June 2018, anytime in these 16 years (data retrieved and observed retrospectively for approximately 1.2 years)

Outcome Measure Data

Analysis Population Description

Analysis population included all eligible participants with mRCC and/or aRCC, received sunitinib as first-line treatment and/or axitinib as second-line treatment from 2002 till 30 June 2018.

Arm/Group Title	Participants With mRCC and/or aRCC: First Line Sunitinib Treatment	Participants With mRCC and/or aRCC: Second Line Axitinib Treatment
Arm/Group Description	Participants who met the selection criteria, diagnosed with mRCC and/or aRCC, received sunitinib as first-line treatment from 2002 till 30 June 2018, according to normal routine healthcare practice in real-world setting, were included in this reporting arm. Data of these participants were derived from Christie NHS database.	Participants who met the selection criteria, diagnosed with mRCC and/or aRCC, received axitinib as second-line treatment from 2002 till 30 June 2018, according to normal routine healthcare practice in real-world setting, were included in this reporting arm. Data of these participants were derived from Christie NHS database.
Measure Participants	622	121
CR	19 2.8%	0 NaN
PR	127 18.6%	17 NaN
SD	252 36.8%	50 NaN
PD	145 21.2%	33 NaN
Surgical CR	2 0.3%	0 NaN
NA/Missing (no clinical response recorded in data base)	77 11.3%	21 NaN

8. Secondary Outcome

Title	Objective Response Rate (ORR)
Description	ORR was defined as the percentage of participants who achieved a BOR of CR or PR as per RECIST v1.1. CR was defined as disappearance of target and non-target lesions and normalization of tumor markers. Pathological lymph nodes must have short axis measures <10 mm. PR was defined as at least a 30% decrease in the sum of measures (longest diameter for tumor lesions and short axis measure for nodes) of target lesions, taking as reference baseline sum of diameters. Non-target lesions must be non-PD. PD was defined as at least a 20% increase in sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to 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 considered progression. Alive participants who did not have event were censored at final study cutoff date.
Time Frame	From start of treatment until CR,PR,PD,death/initiation of new therapy, whichever occurred first, from inception of database(2002) until 30 June 2018, anytime in these 16 years (from data retrieved and observed retrospectively for approximately 1.2 years)

Outcome Measure Data

Analysis Population Description

Analysis population included all eligible participants with mRCC and/or aRCC, received sunitinib as first-line treatment and/or axitinib as second-line treatment from 2002 till 30 June 2018.

Arm/Group Title	Participants With mRCC and/or aRCC: First Line Sunitinib Treatment	Participants With mRCC and/or aRCC: Second Line Axitinib Treatment
Arm/Group Description	Participants who met the selection criteria, diagnosed with mRCC and/or aRCC, received sunitinib as first-line treatment from 2002 till 30 June 2018, according to normal routine healthcare practice in real-world setting, were included in this reporting arm. Data of these participants were derived from Christie NHS database.	Participants who met the selection criteria, diagnosed with mRCC and/or aRCC, received axitinib as second-line treatment from 2002 till 30 June 2018, according to normal routine healthcare practice in real-world setting, were included in this reporting arm. Data of these participants were derived from Christie NHS database.
Measure Participants	622	121
Number (95% Confidence Interval) [Percentage of participants]	23.5 3.4%	14.0 NaN

9. Secondary Outcome

Title	Duration of Response (DOR)
Description	DOR was defined as the time between the date of the first documented confirmed response (PR or CR) and the date of the first documented progression or death due to any cause. Alive participants who did not have event were censored at final study cutoff date. As per RECIST v1.1: CR was defined as disappearance of target and non-target lesions and normalization of tumor markers. Pathological lymph nodes short axis measures <10 mm. PR was defined as at least 30% decrease in sum of measures (tumor lesions- longest diameter and nodes- short axis) of target lesions, taking as reference baseline sum of diameters. PD was defined as at least 20% increase in sum of diameters of measured lesions taking as references smallest sum of diameters recorded on study (including baseline) and an absolute increase of >=5 mm or appearance of at least 1 new lesion.
Time Frame	From date of first documented CR/PR until PD/death/initiation of new therapy, whichever occurred first, from inception of database(2002) until 30 June 2018, anytime in these 16years (data retrieved and observed retrospectively for approximately 1.2 years)

Outcome Measure Data

Analysis Population Description

Analysis population included all eligible participants with mRCC and/or aRCC, received sunitinib as first-line treatment and/or axitinib as second-line treatment from 2002 till 30 June 2018. Required information for this outcome measure was not present in Christie NHS database. Hence, data could not be collected and analyzed for this outcome measure.

Arm/Group Title	Participants With mRCC and/or aRCC: First Line Sunitinib Treatment	Participants With mRCC and/or aRCC: Second Line Axitinib Treatment
Arm/Group Description	Participants who met the selection criteria, diagnosed with mRCC and/or aRCC, received sunitinib as first-line treatment from 2002 till 30 June 2018, according to normal routine healthcare practice in real-world setting, were included in this reporting arm. Data of these participants were derived from Christie NHS database.	Participants who met the selection criteria, diagnosed with mRCC and/or aRCC, received axitinib as second-line treatment from 2002 till 30 June 2018, according to normal routine healthcare practice in real-world setting, were included in this reporting arm. Data of these participants were derived from Christie NHS database.
Measure Participants	0	0

10. Secondary Outcome

Title	Time to Treatment Discontinuation (TTD)
Description	TTD was defined as the time between initiation of treatment to the end of treatment for any reason including PD, death, and lost-to follow up. Participants were censored on the study end date or at last office visit date without clinical or radiographic evidence of PD, whichever occurred first.
Time Frame	From start of the treatment until end of treatment, from inception of database (2002) until 30 June 2018, anytime in these 16 years (from the data retrieved and observed retrospectively for approximately 1.2 years)

Outcome Measure Data

Analysis Population Description

Analysis population included all eligible participants with mRCC and/or aRCC, received sunitinib as first-line treatment and/or axitinib as second-line treatment from 2002 till 30 June 2018.

Arm/Group Title	Participants With mRCC and/or aRCC: First Line Sunitinib Treatment	Participants With mRCC and/or aRCC: Second Line Axitinib Treatment
Arm/Group Description	Participants who met the selection criteria, diagnosed with mRCC and/or aRCC, received sunitinib as first-line treatment from 2002 till 30 June 2018, according to normal routine healthcare practice in real-world setting, were included in this reporting arm. Data of these participants were derived from Christie NHS database.	Participants who met the selection criteria, diagnosed with mRCC and/or aRCC, received axitinib as second-line treatment from 2002 till 30 June 2018, according to normal routine healthcare practice in real-world setting, were included in this reporting arm. Data of these participants were derived from Christie NHS database.
Measure Participants	622	121
Median (95% Confidence Interval) [Months]	8.509	6.899

11. Secondary Outcome

Title	Time to Treatment Discontinuation (TTD): Memorial Sloan-Kettering Cancer Center (MSKCC) Stratification
Description	TTD was defined as the time between initiation of treatment to the end of treatment for any reason including PD, death, and lost-to follow up. Participants were censored on the study end date or at last office visit date without clinical or radiographic evidence of PD, whichever occurred first. MSKCC criteria had following 5 risk factors: KPS <80% (ability to perform ordinary tasks, 0 [dead] -100 [normal]); time from diagnosis to start of systemic therapy <12 months; hemoglobin <LLN; lactate dehydrogenase 1.5*ULN; corrected serum calcium >10.0 mg/dL. Present risk factors were added, and then participants were stratified in following prognosis group: favorable (0 factor), intermediate (1-2 factors), poor (>=3 factors), unknown/missing = no information available.
Time Frame	From start of the treatment until end of treatment, from inception of database (2002) until 30 June 2018, anytime in these 16 years (from the data retrieved and observed retrospectively for approximately 1.2 years)

Outcome Measure Data

Analysis Population Description

Analysis population included all eligible participants with mRCC and/or aRCC, received sunitinib as first-line treatment and/or axitinib as second-line treatment from 2002 till 30 June 2018. Here, "Number Analyzed" signifies number of participants evaluable for specified rows.

Arm/Group Title	Participants With mRCC and/or aRCC: First Line Sunitinib Treatment	Participants With mRCC and/or aRCC: Second Line Axitinib Treatment
Arm/Group Description	Participants who met the selection criteria, diagnosed with mRCC and/or aRCC, received sunitinib as first-line treatment from 2002 till 30 June 2018, according to normal routine healthcare practice in real-world setting, were included in this reporting arm. Data of these participants were derived from Christie NHS database.	Participants who met the selection criteria, diagnosed with mRCC and/or aRCC, received axitinib as second-line treatment from 2002 till 30 June 2018, according to normal routine healthcare practice in real-world setting, were included in this reporting arm. Data of these participants were derived from Christie NHS database.
Measure Participants	622	121
Favorable	15.836	12.649
Intermediate	9.051	8.903
Poor	2.760	1.610
Unknown/missing (no information available)	NA	NA

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Participants With mRCC and/or aRCC: First Line Sunitinib Treatment
	Comments	Data were compared statistically across all 3 categories (favorable, intermediate and poor).
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Log Rank
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Participants With mRCC and/or aRCC: Second Line Axitinib Treatment
	Comments	Data were compared statistically across all 3 categories (favorable, intermediate and poor).
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Log Rank
	Comments

12. Secondary Outcome

Title	Time to Treatment Discontinuation (TTD): International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) Stratification
Description	TTD was defined as the time between initiation of treatment to the end of treatment for any reason including PD, death, and lost-to follow up. Participants were censored on the study end date or at last office visit date without clinical or radiographic evidence of PD, whichever occurred first. IMDC criteria had following 6 risk factors: KPS <80% (ability to perform ordinary tasks, 0 [dead] -100 [normal]); time from diagnosis to start of systemic therapy <12 months; corrected serum calcium >10.0 mg/dL; neutrophils and platelets >LLN and hemoglobin <LLN. Present risk factors were added, and then participants were stratified in following prognosis group: favorable (0 factor), intermediate (1-2 factors), poor (>=3 factors), unknown/missing =no information available.
Time Frame	From start of the treatment until end of treatment, from inception of database (2002) until 30 June 2018, anytime in these 16 years (from the data retrieved and observed retrospectively for approximately 1.2 years)

Outcome Measure Data

Analysis Population Description

Analysis population included all eligible participants with mRCC and/or aRCC, received sunitinib as first-line treatment and/or axitinib as second-line treatment from 2002 till 30 June 2018. Here, "Number Analyzed" signifies number of participants evaluable for specified rows.

Arm/Group Title	Participants With mRCC and/or aRCC: First Line Sunitinib Treatment	Participants With mRCC and/or aRCC: Second Line Axitinib Treatment
Arm/Group Description	Participants who met the selection criteria, diagnosed with mRCC and/or aRCC, received sunitinib as first-line treatment from 2002 till 30 June 2018, according to normal routine healthcare practice in real-world setting, were included in this reporting arm. Data of these participants were derived from Christie NHS database.	Participants who met the selection criteria, diagnosed with mRCC and/or aRCC, received axitinib as second-line treatment from 2002 till 30 June 2018, according to normal routine healthcare practice in real-world setting, were included in this reporting arm. Data of these participants were derived from Christie NHS database.
Measure Participants	622	121
Favorable	15.129	12.649
Intermediate	9.988	7.359
Poor	5.651	3.680
Unknown/missing (no information available)	NA	NA

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Participants With mRCC and/or aRCC: First Line Sunitinib Treatment
	Comments	Data were compared statistically across all 3 categories (favorable, intermediate and poor).
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Log Rank
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Participants With mRCC and/or aRCC: Second Line Axitinib Treatment
	Comments	Data were compared statistically across all 3 categories (favorable, intermediate and poor).
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0094
	Comments
	Method	Log Rank
	Comments

13. Secondary Outcome

Title	Durable Response Rate (DRR)
Description	DRR was determined as the percentage of participants with objective response (CR or PR) with a duration of at least 6 months. As per RECIST v1.1: CR was defined as disappearance of target and non-target lesions and normalization of tumor markers. Pathological lymph nodes short axis measures <10 mm. PR was defined as at least 30% decrease in sum of measures (tumor lesions- longest diameter and nodes- short axis) of target lesions, taking as reference baseline sum of diameters.
Time Frame	6 months from inception of database (2002) until 30 June 2018, anytime in these 16 years (from the data retrieved and observed retrospectively for approximately 1.2 years)

Outcome Measure Data

Analysis Population Description

Analysis population included all eligible participants with mRCC and/or aRCC, received sunitinib as first-line treatment and/or axitinib as second-line treatment from 2002 till 30 June 2018. Required information for this outcome measure was not present in Christie NHS database. Hence, data could not be collected and analyzed for this outcome measure.

Arm/Group Title	Participants With mRCC and/or aRCC: First Line Sunitinib Treatment	Participants With mRCC and/or aRCC: Second Line Axitinib Treatment
Arm/Group Description	Participants who met the selection criteria, diagnosed with mRCC and/or aRCC, received sunitinib as first-line treatment from 2002 till 30 June 2018, according to normal routine healthcare practice in real-world setting, were included in this reporting arm. Data of these participants were derived from Christie NHS database.	Participants who met the selection criteria, diagnosed with mRCC and/or aRCC, received axitinib as second-line treatment from 2002 till 30 June 2018, according to normal routine healthcare practice in real-world setting, were included in this reporting arm. Data of these participants were derived from Christie NHS database.
Measure Participants	0	0

14. Other Pre-specified Outcome

Title	Number of Participants Who Started Systemic Therapy Within 1 Year of Diagnosis
Time Frame	Baseline (data retrieved and observed retrospectively for approximately 1.2 years)

Outcome Measure Data

Analysis Population Description

Analysis population included all eligible participants with mRCC and/or aRCC, received sunitinib as first-line treatment and/or axitinib as second-line treatment from 2002 till 30 June 2018.

Arm/Group Title	Participants With mRCC and/or aRCC: First Line Sunitinib Treatment	Participants With mRCC and/or aRCC: Second Line Axitinib Treatment
Arm/Group Description	Participants who met the selection criteria, diagnosed with mRCC and/or aRCC, received sunitinib as first-line treatment from 2002 till 30 June 2018, according to normal routine healthcare practice in real-world setting, were included in this reporting arm. Data of these participants were derived from Christie NHS database.	Participants who met the selection criteria, diagnosed with mRCC and/or aRCC, received axitinib as second-line treatment from 2002 till 30 June 2018, according to normal routine healthcare practice in real-world setting, were included in this reporting arm. Data of these participants were derived from Christie NHS database.
Measure Participants	622	121
Count of Participants [Participants]	367 53.7%	63 NaN

15. Other Pre-specified Outcome

Title	Number of Participants With Karnofsky Performance Status (KPS) Less Than 80 Percent (%)
Description	KPS: used for rating participant activities of daily living on scale from 0-100, higher score = participant is better able to carry out daily activities. Score range: 100 = normal no complaints; no disease evidence, 90 = able to carry normal activity; minor signs/symptoms of disease, 80 = normal activity with effort; some signs/symptoms, 70 = cares for self; unable to carry on normal activity, 60 = requires occasional assistance, but able to care for most personal needs, 50 = requires considerable assistance and frequent medical care, 40 = disabled; requires special care, assistance, 30 = severely disabled; hospital admission is indicated although death not imminent, 20 = very sick; hospital admission necessary, 10 = moribund; fatal processes progressing rapidly and 0 = dead. The lower the score the worse is survival for most serious illnesses. Here, number of participants with KPS <80% were reported.
Time Frame	Baseline (data retrieved and observed retrospectively for approximately 1.2 years)

Outcome Measure Data

Analysis Population Description

Analysis population included all eligible participants with mRCC and/or aRCC, received sunitinib as first-line treatment and/or axitinib as second-line treatment from 2002 till 30 June 2018.

Arm/Group Title	Participants With mRCC and/or aRCC: First Line Sunitinib Treatment	Participants With mRCC and/or aRCC: Second Line Axitinib Treatment
Arm/Group Description	Participants who met the selection criteria, diagnosed with mRCC and/or aRCC, received sunitinib as first-line treatment from 2002 till 30 June 2018, according to normal routine healthcare practice in real-world setting, were included in this reporting arm. Data of these participants were derived from Christie NHS database.	Participants who met the selection criteria, diagnosed with mRCC and/or aRCC, received axitinib as second-line treatment from 2002 till 30 June 2018, according to normal routine healthcare practice in real-world setting, were included in this reporting arm. Data of these participants were derived from Christie NHS database.
Measure Participants	622	121
Count of Participants [Participants]	89 13%	28 NaN

16. Other Pre-specified Outcome

Title	Number of Participants With Hemoglobin Less Than Lower Limit of Normal (LLN)
Description	In this outcome measure number of participants with hemoglobin less than LLN were reported. For male participants LLN was 130 grams per liter and for female participants LLN was 115 grams per liter.
Time Frame	Baseline (data retrieved and observed retrospectively for approximately 1.2 years)

Outcome Measure Data

Analysis Population Description

Analysis population included all eligible participants with mRCC and/or aRCC, received sunitinib as first-line treatment and/or axitinib as second-line treatment from 2002 till 30 June 2018.

Arm/Group Title	Participants With mRCC and/or aRCC: First Line Sunitinib Treatment	Participants With mRCC and/or aRCC: Second Line Axitinib Treatment
Arm/Group Description	Participants who met the selection criteria, diagnosed with mRCC and/or aRCC, received sunitinib as first-line treatment from 2002 till 30 June 2018, according to normal routine healthcare practice in real-world setting, were included in this reporting arm. Data of these participants were derived from Christie NHS database.	Participants who met the selection criteria, diagnosed with mRCC and/or aRCC, received axitinib as second-line treatment from 2002 till 30 June 2018, according to normal routine healthcare practice in real-world setting, were included in this reporting arm. Data of these participants were derived from Christie NHS database.
Measure Participants	622	121
Count of Participants [Participants]	322 47.1%	72 NaN

17. Other Pre-specified Outcome

Title	Number of Participants With Serum Calcium >Upper Limit of Normal (ULN), Neutrophil >ULN, Platelets >ULN and Lactate Dehydrogenase >1.5*ULN
Description	Number of participants with serum calcium >ULN (3.00 millimole per liter [mmol/L]), neutrophils >ULN (7.5 *10^9/L), platelets >ULN (400 *10^9/L), lactate dehydrogenase >1.5*ULN were reported in this outcome measure.
Time Frame	Baseline (data retrieved and observed retrospectively for approximately 1.2 years)

Outcome Measure Data

Analysis Population Description

Analysis population included all eligible participants with mRCC and/or aRCC, received sunitinib as first-line treatment and/or axitinib as second-line treatment from 2002 till 30 June 2018.

Arm/Group Title	Participants With mRCC and/or aRCC: First Line Sunitinib Treatment	Participants With mRCC and/or aRCC: Second Line Axitinib Treatment
Arm/Group Description	Participants who met the selection criteria, diagnosed with mRCC and/or aRCC, received sunitinib as first-line treatment from 2002 till 30 June 2018, according to normal routine healthcare practice in real-world setting, were included in this reporting arm. Data of these participants were derived from Christie NHS database.	Participants who met the selection criteria, diagnosed with mRCC and/or aRCC, received axitinib as second-line treatment from 2002 till 30 June 2018, according to normal routine healthcare practice in real-world setting, were included in this reporting arm. Data of these participants were derived from Christie NHS database.
Measure Participants	622	121
Serum Calcium >ULN	45 6.6%	7 NaN
Neutrophil >ULN	132 19.3%	11 NaN
Platelets >ULN	181 26.5%	28 NaN
Lactate Dehydrogenase >1.5*ULN	368 53.8%	67 NaN

18. Other Pre-specified Outcome

Title	Number of Participants Per Tumor Fuhrman Grades
Description	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.
Time Frame	Baseline (data retrieved and observed retrospectively for approximately 1.2 years)

Outcome Measure Data

Analysis Population Description

Analysis population included all eligible participants with mRCC and/or aRCC, received sunitinib as first-line treatment and/or axitinib as second-line treatment from 2002 till 30 June 2018.

Arm/Group Title	Participants With mRCC and/or aRCC: First Line Sunitinib Treatment	Participants With mRCC and/or aRCC: Second Line Axitinib Treatment
Arm/Group Description	Participants who met the selection criteria, diagnosed with mRCC and/or aRCC, received sunitinib as first-line treatment from 2002 till 30 June 2018, according to normal routine healthcare practice in real-world setting, were included in this reporting arm. Data of these participants were derived from Christie NHS database.	Participants who met the selection criteria, diagnosed with mRCC and/or aRCC, received axitinib as second-line treatment from 2002 till 30 June 2018, according to normal routine healthcare practice in real-world setting, were included in this reporting arm. Data of these participants were derived from Christie NHS database.
Measure Participants	622	121
1	8 1.2%	0 NaN
2	113 16.5%	21 NaN
3	141 20.6%	34 NaN
4	137 20%	38 NaN
Missing (no information available)	223 32.6%	28 NaN

19. Other Pre-specified Outcome

Title	Number of Participants With Tumor Subtype
Description	In this outcome measure, number of participants were classified according to tumor subtype as clear cell, non-clear cell and unknown/missing.
Time Frame	Baseline (data retrieved and observed retrospectively for approximately 1.2 years)

Outcome Measure Data

Analysis Population Description

Analysis population included all eligible participants with mRCC and/or aRCC, received sunitinib as first-line treatment and/or axitinib as second-line treatment from 2002 till 30 June 2018.

Arm/Group Title	Participants With mRCC and/or aRCC: First Line Sunitinib Treatment	Participants With mRCC and/or aRCC: Second Line Axitinib Treatment
Arm/Group Description	Participants who met the selection criteria, diagnosed with mRCC and/or aRCC, received sunitinib as first-line treatment from 2002 till 30 June 2018, according to normal routine healthcare practice in real-world setting, were included in this reporting arm. Data of these participants were derived from Christie NHS database.	Participants who met the selection criteria, diagnosed with mRCC and/or aRCC, received axitinib as second-line treatment from 2002 till 30 June 2018, according to normal routine healthcare practice in real-world setting, were included in this reporting arm. Data of these participants were derived from Christie NHS database.
Measure Participants	622	121
Clear cell	484 70.8%	102 NaN
Non-clear cell	54 7.9%	7 NaN
Unknown/missing (no information available)	84 12.3%	12 NaN

20. Other Pre-specified Outcome

Title	Number of Participants With Adverse Events
Description	An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship with the study treatment.
Time Frame	From start of treatment until death, from inception of database (2002) until 30 June 2018, anytime in these 16 years (from the data retrieved and observed retrospectively for approximately 1.2 years)

Outcome Measure Data

Analysis Population Description

Minimum criteria for reporting an AE (i.e. identifiable participant, identifiable reporter, a suspect product, and event) could not met, hence, adverse events were not collected and reported.

Arm/Group Title	Participants With mRCC and/or aRCC: First Line Sunitinib Treatment	Participants With mRCC and/or aRCC: Second Line Axitinib Treatment
Arm/Group Description	Participants who met the selection criteria, diagnosed with mRCC and/or aRCC, received sunitinib as first-line treatment from 2002 till 30 June 2018, according to normal routine healthcare practice in real-world setting, were included in this reporting arm. Data of these participants were derived from Christie NHS database.	Participants who met the selection criteria, diagnosed with mRCC and/or aRCC, received axitinib as second-line treatment from 2002 till 30 June 2018, according to normal routine healthcare practice in real-world setting, were included in this reporting arm. Data of these participants were derived from Christie NHS database.
Measure Participants	0	0

Adverse Events

Time Frame	Not applicable as adverse events were not collected during the study
Adverse Event Reporting Description	Minimum criteria for reporting an adverse event (i.e. identifiable participant, identifiable reporter, a suspect product, and event) could not met, hence, adverse events were not collected and reported.
Arm/Group Title	Participants With mRCC and/or aRCC: First Line Sunitinib Treatment		Participants With mRCC and/or aRCC: Second Line Axitinib Treatment
Arm/Group Description	Participants who met the selection criteria, diagnosed with mRCC and/or aRCC, received sunitinib as first-line treatment from 2002 till 30 June 2018, according to normal routine healthcare practice in real-world setting, were included in this reporting arm. Data of these participants were derived from Christie NHS database.		Participants who met the selection criteria, diagnosed with mRCC and/or aRCC, received axitinib as second-line treatment from 2002 till 30 June 2018, according to normal routine healthcare practice in real-world setting, were included in this reporting arm. Data of these participants were derived from Christie NHS database.
All Cause Mortality
	Participants With mRCC and/or aRCC: First Line Sunitinib Treatment		Participants With mRCC and/or aRCC: Second Line Axitinib Treatment
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)
Serious Adverse Events
	Participants With mRCC and/or aRCC: First Line Sunitinib Treatment		Participants With mRCC and/or aRCC: Second Line Axitinib Treatment
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)
Other (Not Including Serious) Adverse Events
	Participants With mRCC and/or aRCC: First Line Sunitinib Treatment		Participants With mRCC and/or aRCC: Second Line Axitinib Treatment
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)

Limitations/Caveats

Data was originally planned to be retrieved and analyzed from the database inception date (2002) until the end of June 2017. However, due to delay in data transfer, data retrieved and analysis was extended from end of June 2017 to end of June 2018. Required information for outcome measures- duration of response and durable response rate was not present in Christie NHS database. Hence, data could not be collected and analyzed for these outcome measures.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.