Clinical Outcomes For Patients With Metastatic Renal Cell Carcinoma (mRCC) Who Received Sunitinib After 1st Line Immune-oncology (IO) Treatments

• Sponsor: Pfizer (Industry)
• Overall Status: Completed
• CT.gov ID: NCT04175262
• Collaborator: IMDC group (Other), Analysis Group (Other)
• Enrollment: 102
• Location: 1
• Actual Duration (Months): 4.3
• Patients Per Site Per Month: 23.9

Study Details

Study Description

Brief Summary

The study aims to assess clinical outcomes in mRCC patients treated with sunitinib in second-line following IO therapy in real world clinical practices.

Condition or Disease	Intervention/Treatment	Phase
Metastatic Renal Cell Carcinoma (mRCC)	Drug: sunitinib

Study Design

• Study Type: Observational
• Actual Enrollment: 102 participants
• Observational Model: Cohort
• Time Perspective: Retrospective
• Official Title: Clinical Effectiveness of Second-Line Sunitinib Following Immune-oncologic (IO) Therapy in Patients With Metastatic Renal Cell Carcinoma in the International Metastatic Renal Cell Carcinoma Database (IMDC)
• Actual Study Start Date: Oct 31, 2019
• Actual Primary Completion Date: Mar 9, 2020
• Actual Study Completion Date: Mar 9, 2020

Arms and Interventions

Arm	Intervention/Treatment
Patients with mRCC Patients diagnosed with metastatic RCC receiving first line (1L) combination of IOs therapies followed by Sunitinib as a second line (2L) treatment	Drug: sunitinib; Patients to receive sunitinib as second line therapy for mRCC

Outcome Measures

Primary Outcome Measures

1. Overall Survival (OS) After Initiation of Second Line Sunitinib Therapy [From the date of initiation of second line sunitinib to the date of death or censored date, up to a maximum of approximately 5.5 years (from the data collected and observed retrospectively for approximately 4 months)]

   Overall survival was defined as the time (in months) from second line sunitinib initiation to death. Participants were censored at their date of last follow-up. Kaplan-Meier method was used for analysis.

2. Time to Treatment Discontinuation (TTD) of Second Line Sunitinib Therapy [From the date of initiation of second line sunitinib to discontinuation or censored date, up to a maximum of approximately 5.5 years (from the data collected and observed retrospectively for approximately 4 months)]

   TTD was defined as the time (in months) between initiation of second line sunitinib therapy and discontinuation of therapy for any reason including progression, death, and toxicity. Participants were censored at their date of last follow-up. As per response evaluation criteria in solid tumors (RECIST) 1.1 criteria: disease progression was at least a 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 at least 1 new lesion. Unequivocal progression of existing non-target lesions. Kaplan-Meier method was used for analysis.

3. Time to Treatment Discontinuation (TTD) of First Line Immune-Oncologic Therapy [From the initiation of immune-oncologic therapy to discontinuation of immune-oncologic therapy (approximately up to 2 years)]

   TTD was defined as the time (in months) between initiation of first line Immune-Oncologic therapy and discontinuation of therapy for any reason including progression, death, and toxicity. Participants were censored at their date of last follow-up. As per RECIST 1.1 criteria: disease progression was at least a 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 mm, or the appearance of at least 1 new lesion. Unequivocal progression of existing non-target lesions. Kaplan-Meier method was used for analysis.

4. Number of Participants Classified According to Reasons for Second-Line Sunitinib Treatment Discontinuation [From the date of initiation of second line sunitinib to discontinuation or censored date, up to a maximum of approximately 5.5 years (from the data collected and observed retrospectively for approximately 4 months)]

   Reasons for treatment discontinuation included disease progression, death, toxicity and other reasons including urosepsis, nausea, vomiting, diarrhea, comorbidity, and other unspecified. As per RECIST v1.1. criteria, disease progression was at least a 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 mm, or the appearance of at least 1 new lesion. Unequivocal progression of existing non-target lesions.

5. Objective Response Rate (ORR) After Initiation of Second Line Sunitinib Therapy [From the date of initiation of second line sunitinib to the date of PR and CR or censored date, up to a maximum of approximately 5.5 years (from the data collected and observed retrospectively for approximately 4 months)]

   The objective response rate was defined as the percentage of participants with partial response (PR) and complete response (CR). As per RECIST 1.1 criteria: CR = disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Disappearance of all non-target lesions and normalisation of tumour marker level. All lymph nodes must be non-pathological in size (<10 mm short axis); PR = at least 30% decrease in sum of diameters of target lesions taking as reference baseline sum diameters.

6. Percentage of Participants With Progressive Disease (PD) After Initiation of Second Line Sunitinib Therapy [From the date of initiation of second line sunitinib to occurrence of disease progression, up to a maximum of approximately 5.5 years (from the data collected and observed retrospectively for approximately 4 months)]

   Progressive disease (PD) was defined as an increase in visible disease. According to RECIST 1.1; PD = at least a 20% increase in the sum of diameters of target lesions taking as reference the smallest sum on the study. This includes the baseline sum if that is the smallest on study. In addition to the relative increase of 20%, the sum also demonstrated an absolute increase of at least 5 mm or the appearance of at least 1 new lesion. Unequivocal progression of existing non-target lesions.

7. Percentage of Participants With Stable Disease (SD) After Initiation of Second Line Sunitinib Therapy [From the date of initiation of second line sunitinib to the date stable disease or censored date, up to a maximum of approximately 5.5 years (from the data collected and observed retrospectively for approximately 4 months)]

   Stable disease was defined as no change in size of visible disease. According to RECIST 1.1, stable disease: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease , taking as reference the smallest sum diameters while on study; PD = at least a 20% increase in the sum of diameters of target lesions taking as reference the smallest sum on the study. This includes the baseline sum if that is the smallest on study. In addition to the relative increase of 20%, the sum also demonstrated an absolute increase of at least 5 mm or the appearance of at least 1 new lesion. Unequivocal progression of existing non-target lesions. PR = at least 30% decrease in sum of diameters of target lesions taking as reference baseline sum diameters.

8. Time From First Line Immune-Oncologic Therapy Discontinuation to Initiation of Second Line Sunitinib Therapy [From the discontinuation of immune-oncologic therapy to the initiation of sunitinib therapy (approximately up to 2 years)]

9. Number of Participants Classified According to Reasons for First-Line Immune-Oncologic Treatment Discontinuation [From the date of initiation of first line Immune-Oncologic to discontinuation or follow-up (approximately up to 2 years)]

   Reasons for treatment discontinuation included disease progression, toxicity and other reasons including itchiness, mouth dryness, comorbidity, and other unspecified. As per RECIST 1.1 criteria: disease progression was at least a 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 mm, or the appearance of at least 1 new lesion. Unequivocal progression of existing non-target lesions.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Patients must meet all of the following inclusion criteria to be eligible for inclusion in the study:

• Diagnosed with mRCC

• Received IO therapy as 1L therapy

• Received sunitinib as 2L therapy

• Age 18 years or over at the time of mRCC diagnosis

• Actively treated at an IMDC clinical center (to avoid incomplete data)

Exclusion Criteria:

None

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Calgary	Calgary	Alberta	Canada	p2n 4n2

Sponsors and Collaborators

• Pfizer
• IMDC group
• Analysis Group

Investigators

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

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Oct 21, 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: NCT04175262
• Other Study ID Numbers: A6181233
• First Posted: Nov 25, 2019
• Last Update Posted: Apr 2, 2021
• Last Verified: Mar 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Additional relevant MeSH terms: Carcinoma; Carcinoma, Renal Cell; Sunitinib

Study Results

Participant Flow

Recruitment Details	Participants included in this study, were diagnosed with metastatic renal cell carcinoma (mRCC), who were treated with sunitinib from 2014 to 2019, after first-line immune-oncologic therapy.
Pre-assignment Detail	In this study, data for participants was collected retrospectively through the international mRCC database consortium (IMDC) database. Data was collected and analyzed during study duration of approximately 4 months.

Arm/Group Title	Sunitinib Following Immune-oncologic Therapy
Arm/Group Description	Participants with mRCC who received sunitinib as second line therapy from 2014 to 2019 after first line immune-oncologic therapy in real world clinical practices were included in this study.
Period Title: Overall Study
STARTED	102
COMPLETED	102
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Sunitinib Following Immune-oncologic Therapy
Arm/Group Description	Participants with mRCC who received sunitinib as second line therapy from 2014 to 2019 after first line immune-oncologic therapy in real world clinical practices were included in this study.
Overall Participants	102
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	61.3 (11.0)
Sex: Female, Male (Count of Participants)
Female	24 23.5%
Male	78 76.5%
Race/Ethnicity, Customized (Count of Participants)
White	54 52.9%
Non-White	48 47.1%
Prior Nephrectomy Status (Count of Participants)
Yes	78 76.5%
No	24 23.5%
Histology Type (Count of Participants)
Clear cell	81 79.4%
Non-clear cell	7 6.9%
Metastatic Sites (Count of Participants)
Greater than (>) 1	77 75.5%
1	6 5.9%
Site of Metastases (Count of Participants)
Lung	36 35.3%
Lymph nodes	26 25.5%
Bone	22 21.6%
Liver	12 11.8%
Brain	8 7.8%
Adrenal gland	7 6.9%
Pancreas	5 4.9%
Other (Soft tissues, kidney, pleura, pelvis, spleen, peritoneum, and perineal fat)	21 20.6%
Participants According to Time From RCC Diagnosis to First Line Therapy (Count of Participants)
Less than (<) 1 year	67 65.7%
Greater than or equal to (>= 1) year	35 34.3%
Karnofsky Performance Status (KPS) (Count of Participants)
< 80%	23 22.5%
>= 80%	68 66.7%
Hemoglobin Level (Count of Participants)
< LLN	57 55.9%
>=LLN	34 33.3%
Serum Corrected Calcium Level (Count of Participants)
> ULN	5 4.9%
Less than or equal to (<=) ULN	78 76.5%
Neutrophil Count (Count of Participants)
> ULN	22 21.6%
<= ULN	68 66.7%
Platelets Count (Count of Participants)
> ULN	17 16.7%
<= ULN	74 72.5%

Outcome Measures

1. Primary Outcome

Title	Overall Survival (OS) After Initiation of Second Line Sunitinib Therapy
Description	Overall survival was defined as the time (in months) from second line sunitinib initiation to death. Participants were censored at their date of last follow-up. Kaplan-Meier method was used for analysis.
Time Frame	From the date of initiation of second line sunitinib to the date of death or censored date, up to a maximum of approximately 5.5 years (from the data collected and observed retrospectively for approximately 4 months)

Outcome Measure Data

Analysis Population Description

Analysis population included all eligible participants whose data was collected and analyzed in this study.

Arm/Group Title	Sunitinib Following Immune-oncologic Therapy
Arm/Group Description	Participants with mRCC who received sunitinib as second line therapy from 2014 to 2019 after first line immune-oncologic therapy in real world clinical practices were included in this study.
Measure Participants	102
Median (95% Confidence Interval) [Months]	15.6

2. Primary Outcome

Title	Time to Treatment Discontinuation (TTD) of Second Line Sunitinib Therapy
Description	TTD was defined as the time (in months) between initiation of second line sunitinib therapy and discontinuation of therapy for any reason including progression, death, and toxicity. Participants were censored at their date of last follow-up. As per response evaluation criteria in solid tumors (RECIST) 1.1 criteria: disease progression was at least a 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 at least 1 new lesion. Unequivocal progression of existing non-target lesions. Kaplan-Meier method was used for analysis.
Time Frame	From the date of initiation of second line sunitinib to discontinuation or censored date, up to a maximum of approximately 5.5 years (from the data collected and observed retrospectively for approximately 4 months)

Outcome Measure Data

Analysis Population Description

Analysis population included all eligible participants whose data was collected and analyzed in this study.

Arm/Group Title	Sunitinib Following Immune-oncologic Therapy
Arm/Group Description	Participants with mRCC who received sunitinib as second line therapy from 2014 to 2019 after first line immune-oncologic therapy in real world clinical practices were included in this study.
Measure Participants	102
Median (95% Confidence Interval) [Months]	5.4

3. Primary Outcome

Title	Time to Treatment Discontinuation (TTD) of First Line Immune-Oncologic Therapy
Description	TTD was defined as the time (in months) between initiation of first line Immune-Oncologic therapy and discontinuation of therapy for any reason including progression, death, and toxicity. Participants were censored at their date of last follow-up. As per RECIST 1.1 criteria: disease progression was at least a 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 mm, or the appearance of at least 1 new lesion. Unequivocal progression of existing non-target lesions. Kaplan-Meier method was used for analysis.
Time Frame	From the initiation of immune-oncologic therapy to discontinuation of immune-oncologic therapy (approximately up to 2 years)

Outcome Measure Data

Analysis Population Description

Analysis population included all eligible participants whose data was collected and analyzed in this study.

Arm/Group Title	Sunitinib Following Immune-oncologic Therapy
Arm/Group Description	Participants with mRCC who received sunitinib as second line therapy from 2014 to 2019 after first line immune-oncologic therapy in real world clinical practices were included in this study.
Measure Participants	102
Mean (Standard Deviation) [Months]	7.4 (8.8)

4. Primary Outcome

Title	Number of Participants Classified According to Reasons for Second-Line Sunitinib Treatment Discontinuation
Description	Reasons for treatment discontinuation included disease progression, death, toxicity and other reasons including urosepsis, nausea, vomiting, diarrhea, comorbidity, and other unspecified. As per RECIST v1.1. criteria, disease progression was at least a 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 mm, or the appearance of at least 1 new lesion. Unequivocal progression of existing non-target lesions.
Time Frame	From the date of initiation of second line sunitinib to discontinuation or censored date, up to a maximum of approximately 5.5 years (from the data collected and observed retrospectively for approximately 4 months)

Outcome Measure Data

Analysis Population Description

Analysis population included all eligible participants whose data was collected and analyzed in this study. Here, "Overall Number of Participants Analyzed" signifies participants who discontinued second line sunitinib treatment.

Arm/Group Title	Sunitinib Following Immune-oncologic Therapy
Arm/Group Description	Participants with mRCC who received sunitinib as second line therapy from 2014 to 2019 after first line immune-oncologic therapy in real world clinical practices were included in this study.
Measure Participants	58
Disease progression	28 27.5%
Toxicity	17 16.7%
Death	3 2.9%
Disease progression and Toxicity	1 1%
Disease progression and Death	1 1%
Other (urosepsis, nausea, vomiting, diarrhea, comorbidity, and other unspecified)	8 7.8%

5. Primary Outcome

Title	Objective Response Rate (ORR) After Initiation of Second Line Sunitinib Therapy
Description	The objective response rate was defined as the percentage of participants with partial response (PR) and complete response (CR). As per RECIST 1.1 criteria: CR = disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Disappearance of all non-target lesions and normalisation of tumour marker level. All lymph nodes must be non-pathological in size (<10 mm short axis); PR = at least 30% decrease in sum of diameters of target lesions taking as reference baseline sum diameters.
Time Frame	From the date of initiation of second line sunitinib to the date of PR and CR or censored date, up to a maximum of approximately 5.5 years (from the data collected and observed retrospectively for approximately 4 months)

Outcome Measure Data

Analysis Population Description

Analysis population included all eligible participants whose data was collected and analyzed in this study.

Arm/Group Title	Sunitinib Following Immune-oncologic Therapy
Arm/Group Description	Participants with mRCC who received sunitinib as second line therapy from 2014 to 2019 after first line immune-oncologic therapy in real world clinical practices were included in this study.
Measure Participants	102
Number (95% Confidence Interval) [Percentage of participants]	22.5 22.1%

6. Primary Outcome

Title	Percentage of Participants With Progressive Disease (PD) After Initiation of Second Line Sunitinib Therapy
Description	Progressive disease (PD) was defined as an increase in visible disease. According to RECIST 1.1; PD = at least a 20% increase in the sum of diameters of target lesions taking as reference the smallest sum on the study. This includes the baseline sum if that is the smallest on study. In addition to the relative increase of 20%, the sum also demonstrated an absolute increase of at least 5 mm or the appearance of at least 1 new lesion. Unequivocal progression of existing non-target lesions.
Time Frame	From the date of initiation of second line sunitinib to occurrence of disease progression, up to a maximum of approximately 5.5 years (from the data collected and observed retrospectively for approximately 4 months)

Outcome Measure Data

Analysis Population Description

Analysis population included all eligible participants whose data was collected and analyzed in this study.

Arm/Group Title	Sunitinib Following Immune-oncologic Therapy
Arm/Group Description	Participants with mRCC who received sunitinib as second line therapy from 2014 to 2019 after first line immune-oncologic therapy in real world clinical practices were included in this study.
Measure Participants	102
Number (95% Confidence Interval) [Percentage of participants]	43.7 42.8%

7. Primary Outcome

Title	Percentage of Participants With Stable Disease (SD) After Initiation of Second Line Sunitinib Therapy
Description	Stable disease was defined as no change in size of visible disease. According to RECIST 1.1, stable disease: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease , taking as reference the smallest sum diameters while on study; PD = at least a 20% increase in the sum of diameters of target lesions taking as reference the smallest sum on the study. This includes the baseline sum if that is the smallest on study. In addition to the relative increase of 20%, the sum also demonstrated an absolute increase of at least 5 mm or the appearance of at least 1 new lesion. Unequivocal progression of existing non-target lesions. PR = at least 30% decrease in sum of diameters of target lesions taking as reference baseline sum diameters.
Time Frame	From the date of initiation of second line sunitinib to the date stable disease or censored date, up to a maximum of approximately 5.5 years (from the data collected and observed retrospectively for approximately 4 months)

Outcome Measure Data

Analysis Population Description

Analysis population included all eligible participants whose data was collected and analyzed in this study.

Arm/Group Title	Sunitinib Following Immune-oncologic Therapy
Arm/Group Description	Participants with mRCC who received sunitinib as second line therapy from 2014 to 2019 after first line immune-oncologic therapy in real world clinical practices were included in this study.
Measure Participants	102
Number (95% Confidence Interval) [Percentage of participants]	33.8 33.1%

8. Primary Outcome

Title	Time From First Line Immune-Oncologic Therapy Discontinuation to Initiation of Second Line Sunitinib Therapy
Time Frame	From the discontinuation of immune-oncologic therapy to the initiation of sunitinib therapy (approximately up to 2 years)

Outcome Measure Data

Analysis Population Description

Analysis population included all eligible participants whose data was collected and analyzed in this study.

Arm/Group Title	Sunitinib Following Immune-oncologic Therapy
Arm/Group Description	Participants with mRCC who received sunitinib as second line therapy from 2014 to 2019 after first line immune-oncologic therapy in real world clinical practices were included in this study.
Measure Participants	102
Mean (Standard Deviation) [Months]	3.1 (6.2)

9. Primary Outcome

Title	Number of Participants Classified According to Reasons for First-Line Immune-Oncologic Treatment Discontinuation
Description	Reasons for treatment discontinuation included disease progression, toxicity and other reasons including itchiness, mouth dryness, comorbidity, and other unspecified. As per RECIST 1.1 criteria: disease progression was at least a 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 mm, or the appearance of at least 1 new lesion. Unequivocal progression of existing non-target lesions.
Time Frame	From the date of initiation of first line Immune-Oncologic to discontinuation or follow-up (approximately up to 2 years)

Outcome Measure Data

Analysis Population Description

Analysis population included all eligible participants whose data was collected and analyzed in this study.

Arm/Group Title	Sunitinib Following Immune-oncologic Therapy
Arm/Group Description	Participants with mRCC who received sunitinib as second line therapy from 2014 to 2019 after first line immune-oncologic therapy in real world clinical practices were included in this study.
Measure Participants	102
Disease progression	53 52%
Toxicity	23 22.5%
Disease progression and Toxicity	1 1%
Other (itchiness, mouth dryness, comorbidity, and other unspecified)	25 24.5%

Adverse Events

Time Frame	Not applicable as adverse events not collected during the study
Adverse Event Reporting Description	Due to the nature of claims database from which data were queried, the minimum criteria for reporting an adverse event (i.e., identifiable participant, identifiable reporter, a suspect product, and event) would not meet, hence safety data was not planned to be collected and reported.
Arm/Group Title	Sunitinib Following Immune-oncologic Therapy
Arm/Group Description	Participants with mRCC who received sunitinib as second line therapy from 2014 to 2019 after first line immune-oncologic therapy in real world clinical practices were included in this study.
All Cause Mortality
	Sunitinib Following Immune-oncologic Therapy
	Affected / at Risk (%)	# Events
Total	0/0 (NaN)
Serious Adverse Events
	Sunitinib Following Immune-oncologic Therapy
	Affected / at Risk (%)	# Events
Total	0/0 (NaN)
Other (Not Including Serious) Adverse Events
	Sunitinib Following Immune-oncologic Therapy
	Affected / at Risk (%)	# Events
Total	0/0 (NaN)

Limitations/Caveats

[Not Specified]

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.