Retrospective Analysis of Clinical Factors Associated With Greater Benefit of Axitinib in Metastatic Renal Cancer (AXILONG Study)
Overview
- Phase
- Not Applicable
- Intervention
- Not specified
- Conditions
- Carcinoma, Renal Cell
- Sponsor
- Pfizer
- Enrollment
- 157
- Locations
- 40
- Primary Endpoint
- Number of Participants With Age Less Than or Equal to (<=) 65 Years and Greater Than (>) 65 Years at Initiation of Axitinib Treatment: Long Responders Versus Refractory Participants
- Status
- Completed
- Last Updated
- 4 years ago
Overview
Brief Summary
Retrospective study to collect data from Patients with advanced/metastatic renal cell carcinoma previously treated with Axitinib under standard clinical practice, to describe the clinical profile of the patients with a long response to Axitinib and to try to identify clinical factors which could be related with the long response to Axitinib, through the comparison between long responder patients and a group of refractory patients
Detailed Description
To describe the clinical profile of patients with a long response to Axitinib and to identify clinical factors which could be related with the long response to Axitinib, through the comparison between long responder patients and a group of refractory patients. For this study are defined as "long responder", those patients who has a Progression Free Survival (PFS) of at least 9 months since the initiation of Axitinib treatment, and "refractory patients" those who have Progression Disease (PD) in the first response assessment since the initiation of Axitinib treatment (estimated PFS ≤3 months\] Secondary Objectives * To describe the efficacy of Axitinib treatment in the long responders group, and in relation with the treatment received before Axitinib, in terms of PFS, ORR, CB, OS, TTP ... * To describe the tolerability and drug management of Axitinib in this population. * To describe treatment received after Axitinib in this population. Study procedures: For the recruitment, the Investigator should review the inclusion / exclusion criteria. In case of patients alive at the moment of the inclusion, the investigator will require them to sign the IC. With the data available in the medical records, the information requested will be recorded in the electronic data collection tool.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Age ≥ 18 years
- •Patients with advanced or metastatic renal cell carcinoma, histologically confirmed, with at least one radiological response assessment
- •Patients who had received Axitinib treatment in second or further line with a PFS ≥9 months or DP (disease progression) at the first tumor assessment.
- •For the patients alive at the moment of the inclusion, patients must have a signed informed consent document
Exclusion Criteria
- •Axitinib received out of the approved indication Patients who do not meet any of the inclusion criteria
Outcomes
Primary Outcomes
Number of Participants With Age Less Than or Equal to (<=) 65 Years and Greater Than (>) 65 Years at Initiation of Axitinib Treatment: Long Responders Versus Refractory Participants
Time Frame: At initiation of axitinib treatment, within axitinib therapy of maximum 5.4 years approximately (from the data collected and observed retrospectively during 1 year)
Number of Participants With International Metastatic Database Consortium (IMDC) Risk Group at Initiation of Axitinib Treatment: Long Responders Versus Refractory Participants
Time Frame: At initiation of axitinib treatment, within axitinib therapy of maximum 5.4 years approximately (from the data collected and observed retrospectively during 1 year)
IMDC risk group stratifies participants with mRCC into poor, intermediate and favorable risk groups based on number of adverse clinical and laboratory parameters present. Favorable-risk group: participants had no poor prognostic factors. Intermediate-risk group: participants had 1 or 2 poor prognostic factors. Poor-risk group: participants had 3 to 6 poor prognostic factors. Poor prognostic factors included KPS score of \<80 at the initiation of treatment, time from diagnosis to metastasis treatment of \<12 months, anemia, hypercalcemia (corrected calcium \>10 mg/dL), neutrophilia and thrombocythemia. In this outcome measure, IMDC risk group (favorable, intermediate, poor: at initiation of axitinib) was compared between long responders and refractory participants.
Number of Participants With 1 or More Different Treatment Lines Before Axitinib Treatment Initiation: Long Responders Versus Refractory Participants
Time Frame: Prior to first dose of axitinib treatment, within axitinib therapy of maximum 5.4 years approximately (from the data collected and observed retrospectively during 1 year)
Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status Before First Line Treatment Initiation: Long Responders Versus Refractory Participants
Time Frame: Prior to first dose of first line treatment, within first line therapy of maximum 6.6 years approximately (from the data collected and observed retrospectively during 1 year)
ECOG: participant's performance status was measured on a 6-point scale: 0= fully active/able to carry on all pre-disease activities without restriction; 1= restricted in physically strenuous activity but ambulatory and able to carry out work of a light and sedentary nature; 2= ambulatory and capable of all self-care, but unable to carry out any work activities, up and about more than 50 percent (%) of waking hours; 3= capable of only limited self-care, confined to bed/chair \>50% of waking hours; 4= completely disabled, cannot carry on any self-care, totally confined to bed/chair: 5= dead. In this outcome measure, data for ECOG status (0, 1, \>=2: before first line treatment initiation), was compared between long responders and refractory participants.
Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status on Axitinib Discontinuation: Long Responders Versus Refractory Participants
Time Frame: On discontinuation of axitinib treatment, within axitinib therapy of maximum 5.4 years approximately (from the data collected and observed retrospectively during 1 year)
ECOG: participant's performance status was measured on a 6-point scale: 0= fully active/able to carry on all pre-disease activities without restriction; 1= restricted in physically strenuous activity but ambulatory and able to carry out work of a light and sedentary nature; 2= ambulatory and capable of all self-care, but unable to carry out any work activities, up and about more than 50 percent (%) of waking hours; 3= capable of only limited self-care, confined to bed/chair \>50% of waking hours; 4= completely disabled, cannot carry on any self-care, totally confined to bed/chair: 5= dead. In this outcome measure, data for ECOG status (0, 1, \>=2: on axitinib discontinuation), was compared between long responders and refractory participants.
Number of Participants With Different Type of Renal Cells Before Axitinib Treatment Initiation: Long Responders Versus Refractory Participants
Time Frame: Prior to first dose of axitinib treatment, within axitinib therapy of maximum 5.4 years approximately (from the data collected and observed retrospectively during 1 year)
In this outcome measure, data for participants who had renal cells with different type of histology as 100% clear cells, 100% non-clear cells, majority component of clear cells and majority component of non-clear cells was compared between long responders and refractory participants.
Number of Participants With Memorial Sloan Kettering Cancer Center (MSKCC) Risk Group at Initiation of Axitinib Treatment: Long Responders Versus Refractory Participants
Time Frame: At initiation of axitinib treatment, within axitinib therapy of maximum 5.4 years approximately (from the data collected and observed retrospectively during 1 year)
MSKCC risk system stratifies participants with mRCC into poor, intermediate and favorable risk groups based on number of adverse clinical and laboratory parameters present. Favorable-risk group: participants had no poor prognostic factors. Intermediate-risk group: participants had 1 or 2 adverse prognostic factors. Poor-risk group: participants had more than 2 poor prognostic factors. Poor prognostic factors included a KPS of \<80 (KPS score quantify participant's general well-being and activities of daily life, based on their functional impairment. KPS score ranges between 0= death to 100= no evidence of disease; higher score means higher ability to perform daily tasks), time from diagnosis to treatment for more than 12 months, serum LDH \>1.5\*ULN, corrected serum calcium level \>10.0 mg/dL and hemoglobin \< LLN.
Number of Participants With Memorial Sloan Kettering Cancer Center (MSKCC) Risk Group on Discontinuation of Axitinib Treatment: Long Responders Versus Refractory Participants
Time Frame: On discontinuation of axitinib treatment, within axitinib therapy during treatment of maximum 5.4 years, approximately (from the data collected and observed retrospectively during 1 year)
MSKCC risk system stratifies participants with mRCC into poor, intermediate and favorable risk groups based on number of adverse clinical and laboratory parameters present. Favorable-risk group: participants had no poor prognostic factors. Intermediate-risk group: participants had 1 or 2 adverse prognostic factors. Poor-risk group: participants had more than 2 poor prognostic factors. Poor prognostic factors included a KPS of \<80 (KPS score quantify participant's general well-being and activities of daily life, based on their functional impairment. KPS score ranges between 0= death to 100= no evidence of disease; higher score means higher ability to perform daily tasks), time from diagnosis to treatment for more than 12 months, serum LDH \>1.5\*ULN, corrected serum calcium level \>10.0 mg/dL and hemoglobin \< LLN.
Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status at Initiation of Axitinib Treatment: Long Responders Versus Refractory Participants
Time Frame: At initiation of axitinib treatment, within axitinib therapy of maximum 5.4 years approximately (from the data collected and observed retrospectively during 1 year)
ECOG: participant's performance status was measured on a 6-point scale: 0= fully active/able to carry on all pre-disease activities without restriction; 1= restricted in physically strenuous activity but ambulatory and able to carry out work of a light and sedentary nature; 2= ambulatory and capable of all self-care, but unable to carry out any work activities, up and about more than 50 percent (%) of waking hours; 3= capable of only limited self-care, confined to bed/chair \>50% of waking hours; 4= completely disabled, cannot carry on any self-care, totally confined to bed/chair: 5= dead. In this outcome measure, data for ECOG status (0, 1, \>=2: at initiation of axitinib), was compared between long responders and refractory participants.
Number of Participants With Nephrectomy Procedure Status Before Axitinib Treatment Initiation: Long Responders Versus Refractory Participants
Time Frame: Prior to first dose of axitinib treatment, within axitinib therapy of maximum 5.4 years approximately (from the data collected and observed retrospectively during 1 year)
Nephrectomy is a surgical removal of kidney. Data for participants was categorized as yes and no to depict their nephrectomy status before axitinib treatment initiation and comparison was done between long responders and refractory participants.
Number of Participants With Different Metastatic Sites Locations at Diagnosis of Advance or Metastatic Renal Cell Carcinoma Before Axitinib Treatment Initiation: Long Responders Versus Refractory Participants
Time Frame: At diagnosis of advance or mRCC prior to first dose of first line treatment, within first line therapy of maximum 6.6 years approximately (from the data collected and observed retrospectively during 1 year)
In this outcome measure, data for participants with different metastatic sites as lymph nodes, central nervous system (CNS), hepatic, pulmonary, bone and another site of metastasis at diagnosis of advance or mRCC before axitinib treatment initiation, was compared between long responders and refractory participants.
Number of Participants With Laboratory Parameters at Initiation of First Line Treatment: Long Responders Versus Refractory Participants
Time Frame: At initiation of first line treatment, within first line therapy of maximum 6.6 years approximately (from the data collected and observed retrospectively during 1 year)
In this outcome measure, data for different laboratory parameters at initiation of first line treatment: LDH level \>1.5\*ULN, haemoglobin (Hgb) levels \<=LLN, corrected Ca levels \>10 mg/dL, neutrophil levels \>ULN, platelet levels \>ULN and neutrophil-to-lymphocyte ratio of \<=3 was compared between long responders and refractory participants.
Number of Participants With Memorial Sloan Kettering Cancer Center (MSKCC) Risk Group Before First Line Treatment Initiation: Long Responders Versus Refractory Participants
Time Frame: Prior to first dose of first line treatment, within first line therapy of maximum 6.6 years approximately (from the data collected and observed retrospectively during 1 year)
MSKCC risk system stratifies participants with mRCC into poor, intermediate and favorable risk groups based on number of adverse clinical and laboratory parameters present. Favorable-risk group: participants had no poor prognostic factors. Intermediate-risk group: participants had 1 or 2 adverse prognostic factors. Poor-risk group: participants had more than 2 poor prognostic factors. Poor prognostic factors included a Karnofsky performance status (KPS) of less than (\<) 80 (KPS score quantify participant's general well-being and activities of daily life, based on their functional impairment. KPS score ranges between 0= death to 100= no evidence of disease; higher score means higher ability to perform daily tasks), time from diagnosis to treatment for more than 12 months, serum lactate dehydrogenase (LDH) \>1.5\*upper limit of normal (ULN), corrected serum calcium level \>10.0 milligram per deciliter (mg/dL) and hemoglobin \< lower limit of normal (LLN).
Number of Participants With International Metastatic Database Consortium (IMDC) Risk Group on Discontinuation of Axitinib Treatment: Long Responders Versus Refractory Participants
Time Frame: On discontinuation of axitinib treatment, within axitinib therapy of maximum 5.4 years approximately (from the data collected and observed retrospectively during 1 year)
IMDC risk group stratifies participants with mRCC into poor, intermediate and favorable risk groups based on number of adverse clinical and laboratory parameters present. Favorable-risk group: participants had no poor prognostic factors. Intermediate-risk group: participants had 1 or 2 poor prognostic factors. Poor-risk group: participants had 3 to 6 poor prognostic factors. Poor prognostic factors included KPS score of \<80 at the initiation of treatment, time from diagnosis to metastasis treatment of \<12 months, anemia, hypercalcemia (corrected calcium \>10 mg/dL), neutrophilia and thrombocythemia. In this outcome measure, IMDC risk group (favorable, intermediate, poor: on discontinuation of axitinib) was compared between long responders and refractory participants.
Number of Participants With Duration of First Line Treatment With Tyrosine Kinase Inhibitor (TKI) Before Axitinib Treatment Initiation: Long Responders Versus Refractory Participants
Time Frame: First dose of first line treatment, within first line therapy of maximum 6.6 years approximately (from the data collected and observed retrospectively during 1 year)
Duration of first line treatment with TKI was stratified into 0-3 months, 3-6 months, 6-9 months, 9-12 months and \>12 months and compared between long responders and refractory participants.
Number of Participants With 1 or More Metastatic Locations at Diagnosis of Advance or Metastatic Renal Cell Carcinoma Before First Line Treatment Initiation: Long Responders Versus Refractory Participants
Time Frame: At diagnosis of advance or mRCC prior to first dose of first line treatment, within first line therapy of maximum 6.6 years approximately (from the data collected and observed retrospectively during 1 year)
Number of Participants With Best Response to First Line Treatment With Tyrosine Kinase Inhibitor (TKI) Before Axitinib Treatment Initiation: Long Responders Versus Refractory Participants
Time Frame: First dose of first line treatment, within first line therapy of maximum 6.6 years approximately (from the data collected and observed retrospectively during 1 year)
In this outcome measure, data for participants with their best response as complete response (CR) and partial response (PR), stable disease (SD) or progressive-disease (PD) to the first line treatment with TKI, was compared between long responders and refractory participants. As per response evaluation criteria in solid tumors (RECIST) 1.1 criteria: CR = disappearance of all target lesions. PR = greater than equal to (\>=) 30% decrease in sum of target lesions taking as reference baseline sum diameters. PD: \>= 20% increase in sum of diameters of target lesions, taking as a reference smallest sum on treatment, the sum must also demonstrate an absolute increase of at least 5 millimeter (mm), or the appearance of \>=1 new lesions. SD =neither shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum of diameters during treatment.
Number of Participants With Smoking Habits at Initiation of First Line Treatment: Long Responders Versus Refractory Participants
Time Frame: At initiation of first line treatment, within first line therapy of maximum 6.6 years approximately (from the data collected and observed retrospectively during 1 year)
In this outcome measure, data for smoking habit of participants was compared between long responders and refractory participants.
Secondary Outcomes
- Clinical Benefit Rate (CBR) to Axitinib as the Second Line of Treatment and Subsequent Treatment in Group of Long Responders(From first dose of axitinib as second line of treatment and from first dose of axitinib as subsequent treatment up to a maximum axitinib therapy duration of 5.4 years approximately (data collected and observed retrospectively for 1 year))
- Progression-free Survival (PFS) to Axitinib as Second Line of Treatment and Subsequent Treatment in Group of Long Responders(From first dose of axitinib as second line and from first dose of axitinib as subsequent lines to PD/death by any cause/date of latest follow-up if censored up to a max. axitinib therapy of 5.4 yrs. approx. (data collected, observed retrospectively 1 yr.))
- Percentage of Participants With Reduced Doses of Axitinib of More Than 5 Milligram (mg) Twice Daily: All Participants(For maximum axitinib treatment duration of 5.4 years, approximately (data collected and observed retrospectively for 1 year))
- Progression-free Survival (PFS) to Axitinib Treatment in Group of Long Responders(Day 1 of axitinib dose to disease progression or death due to any cause or date of latest follow-up in case of censored up to a maximum axitinib therapy of 5.4 years, approximately (from the data collected and observed retrospectively during 1 year))
- Overall Survival (OS) From Axitinib Treatment in Group of Long Responders(Day 1 of axitinib dose to death due to any cause or date of latest follow-up in case of censored up to a maximum axitinib therapy of 5.4 years, approximately (from the data collected and observed retrospectively during 1 year))
- Number of Participants With Best Response to Axitinib as Second Line of Treatment and Subsequent Treatment in Group of Long Responders(From first dose of axitinib as second line of treatment and from first dose of axitinib as subsequent treatment up to a maximum axitinib therapy duration of 5.4 years approximately (data collected and observed retrospectively for 1 year))
- Time to Progression (TTP) to Axitinib Treatment in Group of Long Responders(Day 1 of axitinib dose to disease progression or date of latest follow-up in case of censored up to a maximum (max.)axitinib therapy duration of 5.4 years(yrs.)approximately(approx.)(from the data collected, observed retrospectively during 1 year [yr.]))
- Objective Response Rate (ORR) to Axitinib as Second Line of Treatment and Subsequent Treatment in Group of Long Responders(From first dose of axitinib as second line of treatment and from first dose of axitinib as subsequent treatment up to a maximum axitinib therapy duration of 5.4 years approximately (data collected and observed retrospectively for 1 year))
- Time to Progression (TTP) to Axitinib as the Second Line of Treatment and Subsequent Treatment in Group of Long Responders(From first dose of axitinib as second line of treatment and from first dose of axitinib as subsequent treatment to PD/date of latest follow-up if censored up to max. treatment duration of 5.4 yrs., approx. (data collected, observed retrospectively 1 year))
- Overall Survival (OS) to Axitinib as the Second Line of Treatment and Subsequent Treatment in Group of Long Responders(From first dose of axitinib as second line of treatment and from first dose of axitinib as subsequent treatment to death due to any cause/date of latest follow-up if censored upto max. of 5.4 yrs., approx. (data collected, observed retrospectively 1 year))
- Duration of Axitinib Treatment: All Participants(Day 1 of axitinib treatment to end of treatment or date of latest follow-up if not suspended for maximum axitinib therapy duration of 5.4 years, approximately (from data collected and observed retrospectively for 1 year))
- Number of Participants Receiving Subsequent Treatment Post Axitinib Treatment: All Participants(Upon initiation of subsequent treatment (post axitinib treatment) to a maximum subsequent treatment duration of 2.9 years approximately (from data collected and observed retrospectively for 1 year))
- Number of Participants With Reasons to Discontinue Subsequent Treatments Post Axitinib Treatment: All Participants(From initiation of subsequent treatment (post axitinib treatment) to a maximum subsequent treatment duration of 2.9 years approximately (from data collected and observed retrospectively for 1 year))
- Percentage of Participants With Titrated (Increased) Doses of Axitinib of More Than 5 Milligram (mg) Twice Daily: All Participants(For maximum axitinib treatment duration of 5.4 years, approximately (from data collected and observed retrospectively for 1 year))
- Number of Participants as Per Number of Subsequent Lines of Treatment Received Post Axitinib Treatment: All Participants(Upon initiation of subsequent treatment (post axitinib treatment) to a maximum subsequent treatment duration of 2.9 years approximately (from data collected and observed retrospectively for 1 year))
- Number of Participants With Adverse Events (AE): All Participants(For first line treatment: maximum of 6.6 years approximately; for axitinib treatment: maximum of 5.4 years approximately; for post-axitinib subsequent treatments: maximum of 2.9 years approximately (data collected and observed retrospectively for 1 year))
- Number of Participants With First Best Response to Subsequent Treatments Post Axitinib Treatment(From initiation of subsequent treatment (post axitinib treatment) to a maximum subsequent treatment duration of 2.9 years approximately (from data collected and observed retrospectively for 1 year))
- Overall Survival (OS) From Subsequent Treatments Post Axitinib Treatment(From initiation of subsequent treatment (post axitinib treatment) to a maximum subsequent treatment duration of 2.9 years approximately (from data collected and observed retrospectively for 1 year))
- Duration of Subsequent Treatments Post Axitinib Treatment: All Participants(Upon initiation of subsequent treatment (post axitinib treatment) to a maximum subsequent treatment duration of 2.9 years approximately (from data collected and observed retrospectively for 1 year))