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

Study Overview
=================
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: 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)? 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)?

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: 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)? 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: What is the overall survival (OS) of all patients in first line with sunitinib, and stratified by MSKCC risk (favourable, intermediate, poor)? 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) Objective response rate (ORR) Duration of objective response (complete response [CR] or partial response [PR]) Examine factors that predict TTD, e.g. risk stratification, or individual/grouped parameters that comprise the prognostic classification systems Less than one year from time of diagnosis Karnovsky performance status less than 80% Haemoglobin less than the lower limit of normal (e.g. less than 12 g/dl) Serum calcium great than the upper limit of normal (e.g. 10 mg/dl or : 2.5 mmol/l) Neutrophil greater than the upper limit of normal (e.g. greater than 7.0 x109 dl) Platelets greater than the upper limit of normal (e.g. greater than 400 000) Lactate dehydrogenase greater than 1.5 times the upper limit of normal Fuhrmann grade of tumour Tumour subtype e.g. clear cell versus. non-clear cell Safety and tolerability data reporting for first line sunitinib Second line: What is the OS of all patients in second line with axitinib, and stratified by MSKCC risk (favourable, intermediate, poor)? What is the duration of therapy with axitinib in second line (using TTD) for all patients and stratified by MSKCC risk (favourable, intermediate, poor) ORR Duration of objective response (CR or PR) Examine factors that predict duration of TTD, e.g. risk stratification, or individual/grouped parameters that comprise the prognostic classification systems Less than one year from time of diagnosis Karnovsky performance status less than 80% Haemoglobin less than the lower limit of normal (e.g. less than 12 g/dl) Serum calcium great than the upper limit of normal (e.g. 10 mg/dl or : 2.5 mmol/l) Neutrophil greater than the upper limit of normal (e.g. greater than 7.0 x109 dl) Platelets greater than the upper limit of normal (e.g. greater than 400 000) Lactate dehydrogenase greater than 1.5 times the upper limit of normal Fuhrmann grade of tumour Tumour subtype e.g. clear cell vs. non-clear cell 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: Axitinib PFS and OS, as a second line therapy following sunitinib, pazopanib, or following other Tyrosine kinase inhibitors (e.g. sorafenib) Axitinib PFS and OS as a third line therapy 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 For the post-sunitinib axitinib cohort: What was the duration of sunitinib therapy before patients transitioned to axitinib? For the post-pazopanib axitinib cohort: What was the duration of sunitinib therapy before patients transitioned to axitinib? Is the duration of therapy on first line sunitinib and/or pazopanib related to duration of therapy for second line axitinib?

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

Conditions
-----------------
Carcinoma, Renal Cell

Intervention / Treatment
-----------------
* Drug: Sunitinib
* Drug: Axitinib


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion criteria Over the age of 18 years Diagnosis of renal cell carcinoma Treatment with sunitinib and/or axitinib 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: Under the age of 18 years Diagnosis other than renal cell carcinoma No treatment with sunitinib and/or axitinib

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Patients with advanced RCC<br>Patients with a diagnosis of kidney cancer (renal cell carcinoma, advanced or metastatic) | Drug: Sunitinib<br>* Tyrosine kinase inhibitor, licensed for use in treatment of renal cell carcinoma.<br>* Other names: Sutent;Drug: Axitinib<br>* Tyrosine kinase inhibitor, licensed for use in treatment of renal cell carcinoma.<br>* Other names: Inlyta;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS) | 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. | 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) | 
| Progression Free Survival (PFS): Memorial Sloan-Kettering Cancer Center (MSKCC) Stratification | 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. | 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) | 
| Progression Free Survival (PFS): International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) Stratification | 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. | 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) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | 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. | 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) | 
| Overall Survival (OS): Memorial Sloan-Kettering Cancer Center (MSKCC) Stratification | 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. | 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) | 
| Overall Survival (OS): International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) Stratification | 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. | 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) | 
| 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 | 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. | 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) | 
| Objective Response Rate (ORR) | 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. | 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) | 
| Duration of Response (DOR) | 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. | 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) | 
| Time to Treatment Discontinuation (TTD) | 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. | 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) | 
| Time to Treatment Discontinuation (TTD): Memorial Sloan-Kettering Cancer Center (MSKCC) Stratification | 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. | 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) | 
| Time to Treatment Discontinuation (TTD): International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) Stratification | 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. | 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) | 
| Durable Response Rate (DRR) | 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. | 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) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Carcinoma;, renal cell;, cancer;, kidney;, sunitinib;, axitinib