Neoplasms

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Rare Diseases

Carcinoma

Carcinoma, Renal Cell

Adenocarcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Kidney Neoplasms

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Kidney Diseases

Urologic Diseases

Male Urogenital Diseases

Renal Cell Carcinoma

Clear Cell Renal Cell Carcinoma

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Everolimus

Sirolimus

Temsirolimus

MTOR Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Immunosuppressive Agents

Immunologic Factors

everolimis

Novartis Pharmaceuticals

This is a Norwegian prospective registration, observational study of patients with advanced renal cell cancer on Afinitor treatment after failure of one Tyrosine Kinase Inhibitor (TKI) ( e.g. sunitinib or sorafenib). The goal is to document the treatment algorithm of these patients in Norway and the efficacy and tolerability of Afinitor® in a pure 2.line setting.

A Norwegian Observational Trial Evaluating the Treatment of Advanced Renal Cell Cancer Patients Under Treatment of Afinitor

Observational Study Evaluating Efficacy, Tolerability and Treatment Algorithm of Advanced Renal Cell Cancer Patients Under Afinitor Treatment

This will partly be assessed by registration of compliance (patient booklet), QoL and safety. Safety assessments will consist of monitoring and recording adverse events and serious adverse events.

Sunitinib

Angiogenesis Inhibitors

Growth Inhibitors

Patients diagnosed with metastatic RCC receiving first line (1L) combination of IOs therapies followed by Sunitinib as a second line (2L) treatment

Patients to receive sunitinib as second line therapy for mRCC

sunitinib

Pfizer CT.gov Call Center

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

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

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)

Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

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.

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.

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.

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.

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.

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.

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.

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.

IMDC group

Analysis Group

Pfizer

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.

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.

Sunitinib Following Immune-oncologic Therapy

Age, Continuous

Sex: Female, Male

Race

Race/Ethnicity, Customized

Here, number of participants with their previous nephrectomy status as "Yes" or "No" are reported.

Prior Nephrectomy Status

Here, number of participants with histology type as "Clear cell" or "Non-clear cell" are reported.

Here 'number analyzed" signifies participants evaluable for this baseline measure.

Histology Type

Here, number of participants are classified according to number of metastatic sites.

Metastatic Sites

Lung

Lymph nodes

Bone

Liver

Brain

Adrenal gland

Pancreas

Other (Soft tissues, kidney, pleura, pelvis, spleen, peritoneum, and perineal fat)

Here, number of participants are classified according to type of metastatic sites.

Here 'Number analyzed" signifies participants evaluable for this baseline measure.

Site of Metastases

Here, number of participants are classified according to duration of RCC diagnosis to first line therapy.

Participants According to Time From RCC Diagnosis to First Line Therapy

KPS is a standard way of measuring the ability of participants with cancer to perform ordinary tasks. KPS scores range from 0 percent (%) (dead) to 100% (normal, no complaints). A higher score means the participant is better able to carry out daily activities. Here, number of participants are classified with KPS score of \<80% and \>=80%.

Karnofsky Performance Status (KPS)

Here, number of participants are classified with hemoglobin level \< lower limit normal (LLN) and \>= LLN.

Hemoglobin Level

Here, number of participants are classified with serum corrected calcium level \> upper limit normal (ULN) and \<= ULN.

Serum Corrected Calcium Level

Here, number of participants are classified with neutrophil count \> ULN and \<= ULN.

Neutrophil Count

Here, number of participants are classified with platelets count \> ULN and \<= ULN.

Platelets Count

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

Pfizer ClinicalTrials.gov Call Center

Overall Survival (OS) After Initiation of Second Line Sunitinib Therapy

Time to Treatment Discontinuation (TTD) of Second Line Sunitinib Therapy

Time to Treatment Discontinuation (TTD) of First Line Immune-Oncologic Therapy

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.

Number of Participants Classified According to Reasons for Second-Line Sunitinib Treatment Discontinuation

Objective Response Rate (ORR) After Initiation of Second Line Sunitinib Therapy

Percentage of Participants With Progressive Disease (PD) After Initiation of Second Line Sunitinib Therapy

Percentage of Participants With Stable Disease (SD) After Initiation of Second Line Sunitinib Therapy

Time From First Line Immune-Oncologic Therapy Discontinuation to Initiation of Second Line Sunitinib Therapy

Number of Participants Classified According to Reasons for First-Line Immune-Oncologic Treatment Discontinuation

Overall Study

Everolimus 10 mg orally once daily until disease progression, occurrence of intolerable toxicity, start of another anticancer treatment or withdrawn consent.

Everolimus was used as commercially available formulated tablets of 10 mg strength

Everolimus (RAD001)

Patients with metastatic renal cell carcinoma (mRCC) who failed first-line therapy with sunitinib or pazopanib was treated with everolimus. Efficacy and safety of everolimus was evaluated in these patients.

Safety and Efficacy of Everolimus in Metastatic Renal Cell Carcinoma After Failure of First Line Therapy With Sunitinib or Pazopanib

An Open Label, Single Arm Trial to Evaluate Patients With Metastatic Renal Cell Carcinoma Treated With Everolimus After Failure of First Line Therapy With Sunitinib or Pazopanib

Percentage of progression-free patients by month 6 after starting everolimus treatment. For the purpose of the binomial design of the study, a patient being 'progression-free' will be defined as a patient without disease progression by month 6 whereas a subject with progressive disease by month 6 will not be counted as 'progression-free'. The primary variable was derived from radiologic tumor assessments according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1.) Disease progression was either 1) a 20% increase in the sum of the longest diameter of all target lesions, taking as reference the smallest sum of the longest diameters of all target lesions recorded at or after baseline (minimum absolute increase 5 mm in sum) or 2) the appearance of a new lesion or 3) the unequivocal progression of non-target lesions overall.

Overall response rate (ORR) is the Percentage of patients with a best overall response of complete response (CR) or partial response (PR) by month 6. ORR was assessed according to RECIST 1.1 criteria. Partial response (PR) required at least a 30% decrease in the sum of the longest diameters of all target lesions, taking as reference the baseline sum of the longest diameters. Complete response (CR) required a disappearance of all target and non-target lesions.

Progression-free survival (PFS) is the time from date of start of treatment to the date of event defined as the first documented progression or death due to any cause. If a patient did not have an event, progression-free survival was censored at the date of last adequate tumor assessment

Overall survival (OS) was defined as the time from date of start of treatment to date of death due to any cause. If a patient was not known to have died, survival will be censored at the date of last contact.

The duration of overall response (DOR) was defined as the time from the first occurrence of a confirmed Complete Response (CR) or Partial Response (PR) (as per investigator assessment according to RECIST 1.1) until the date of the first documented disease progression or death due to underlying cancer. If a patient did not have an event or received any further anticancer therapy, duration of overall response was censored at the date of last adequate tumor assessment. Duration of response was displayed only for patients whose best overall response was CR or PR. As none of the patients showed any response (CR or PR), DOR could not be calculated

Patients that failed 1st line therapy Sunitinib (SUN) prior to starting study. Patients were on Everolimus 10 mg orally once daily until disease progression, occurrence of intolerable toxicity, start of another anticancer treatment or withdrawn consent.

1st Line SUN

Patients that failed 1st line therapy Pazopanib (PAZ) prior to starting study. Patients were on Everolimus 10 mg orally once daily until disease progression, occurrence of intolerable toxicity, start of another anticancer treatment or withdrawn consent.

1st Line PAZ

Everolimus - All Patients that failed 1st line SUN and 1st Line PAZ and was on Everolimus 10mg orally once daily

Everolimus All Patients

Total

Demographic and other baseline data (including disease characteristics) were summarized descriptively for all patients for the FAS. The full analysis set (FAS) consisted of all patients who received at least one dose of everolimus.

Study Director

Full Analysis Set (FAS) consisted of all patients who received at least one dose of everolimus.

Percentage of Progression-free Patients by Month 6

Percentage of Patients With Overall Response Rate (ORR) Treated With Everolimus After Failure of First-line Sunitinib or Pazopanib Therapy at Month 6

Progression-Free Survival (PFS) as the Time Interval Between First Intake of Everolimus and First Documented Disease Progression or Death Due to Any Cause at 24 Months

Overall Survival (OS) of Patients Treated With Everolimus After Failure of First-line Sunitinib or Pazopanib Therapy up to 48 Months

Duration of response was displayed only for patients whose best overall response was CR or PR. As none of the patients showed any response (CR or PR), DOR could not be calculated

Duration of Response (DOR) in Patients Treated With Everolimus After Failure of First-line Sunitinib or Pazopanib Therapy up to 48 Months

Immunomodulating Agents

The purpose of this study is to learn about the effectiveness of the first and later lines of medicines on clinical outcomes in people with mRCC.

The study includes participants who:

* are 18 years old or above and have mRCC
* took medicines that use the bodies immunity to fight against cancer as their first choice of treatment
* took other medicines after taking the above first choice of treatment

This is a study that looks into the data collected through a particular database from selected academic clinical sites participating in this study. The data of interest include:

* the length of time between the start of a patient's treatment and the end of treatment
* the length of time between the start of treatment and death
* physician assessment of a patient's response to treatment

We will compare the experiences of people receiving different combinations of treatments and see if there are any differences in the effectiveness of these medicines.

A Study to Learn About the First and Later Lines of Medicines in Treating People With Metastatic Renal Cell Carcinoma (mRCC).

Clinical Effectiveness of First-Line Immuno-oncology (IO) Combination Treatment and Subsequent Lines of Therapy in Patients With Metastatic Renal Cell Carcinoma (mRCC) in the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC)

Gender Age at time of 1L initiation Race Region indicator (i.e., US vs. ex-US)

Histology type (i.e., clear cell vs. non-clear cell RCC) Number of metastatic sites (e.g., 1 site or more than 1 site) Site of metastases (e.g., brain, bone, lung)

Assessed on index date and at initiation of each LOT

Defined as the time from treatment initiation to discontinuation of each therapy due to any reason including progression, death, or toxicity

Defined as time from the initiation of 1L treatment to initiation of subsequent therapy or death

Overall best response rate (complete or partial) Stable disease Progressive disease

Defined as the time between initiation of 1L IO combination therapy to death

Lenvatinib

Bevacizumab

Pembrolizumab

Avelumab

Axitinib

Nivolumab

Atezolizumab

Ipilimumab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

collect global experiences with the use of immuno-combinations in patients with metastatic RCC

pembrolizumab plus axitinib

Matteo Santoni, MD, PhD

Giulia Sorgentoni, PhD

The ARON-1 Study is designed as an International Multicentric Retrospective Study to collect global experiences with the use of immuno-combinations in patients with metastatic RCC.

Two Supplementary Studies (ARON-1α and ARON-1β) have been designed. The ARON-1α Supplementary Study has been designed to investigate for the presence of genomic signatures from tumor samples of patients treated with first-line immuno-combinations for advanced RCC. The ARON-1β Supplementary Study has been designed to charaterize the immune cell populations and assess their relationship with the clinical outcome of mRCC patients treated with first-line immuno-combinations

International Multicentric Study ARON-1

Data on tumor assessment and response to therapy on elderly populaton will be statistically analyzed

Data on tumor assessment and response to therapy will be statistically analyzed

Statistical analysis of prognostic role of smoking attitude and obesity in treated RCC patients

Data on tumor assessment and response to therapy in non-clear RCC will be statistically analyzed

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Norwegian Observational Trial Evaluating the Treatment of Advanced Renal Cell Cancer Patients Under Treatment of Afinitor	NCT01390519	Metastatic Rena...	everolimis	18 Years -	Novartis
Clinical Outcomes For Patients With Metastatic Renal Cell Carcinoma (mRCC) Who Received Sunitinib After 1st Line Immune-oncology (IO) Treatments	NCT04175262	Metastatic Rena...	sunitinib	18 Years -	Pfizer
Safety and Efficacy of Everolimus in Metastatic Renal Cell Carcinoma After Failure of First Line Therapy With Sunitinib or Pazopanib	NCT01514448	Metastatic Rena...	Everolimus (RAD...	18 Years -	Novartis
A Norwegian Observational Trial Evaluating the Treatment of Advanced Renal Cell Cancer Patients Under Treatment of Afinitor	NCT01390519	Metastatic Rena...	everolimis	18 Years -	Novartis
A Study to Learn About the First and Later Lines of Medicines in Treating People With Metastatic Renal Cell Carcinoma (mRCC).	NCT05858749	Metastatic Rena...		18 Years -	Pfizer
A Study to Learn About the First and Later Lines of Medicines in Treating People With Metastatic Renal Cell Carcinoma (mRCC).	NCT05858749	Metastatic Rena...		18 Years -	Pfizer
International Multicentric Study ARON-1	NCT05287464	Metastatic Rena...	pembrolizumab p...	18 Years -	Hospital of Macerata

Spots Global Cancer Trial Database for metastatic renal cell carcinoma (mrcc)