Anemia, Bladder Cancer, Breast Cancer, Cancer, Colorectal Cancer, Endometrial Cancer, Esophageal Cancer, Gastric Cancer, Lung Cancer, Ovarian Cancer, Pancreatic Cancer, Prostate Cancer, Renal Cancer, Solid Tumors
Conditions
Keywords
Breast Cancer, Lung Cancer, Ovarian Cancer, Prostate Cancer, Colorectal Cancer, Aranesp, Chemotherapy induced anaemia, Chemotherapy, Bladder Cancer, Endometrial Cancer, Renal Cancer, Pancreatic Cancer, Esophageal Cancer, Gastric Cancer
Brief summary
This is a multicenter, international, prospective, observational study of patients who are receiving systemic chemotherapy for solid tumour cancers (breast, colorectal, ovarian, prostate, lung, bladder, endometrial, renal, pancreatic, esophageal or gastric) and who are receiving darbepoetin alfa (Aranesp®) or other erythropoiesis-stimulating agent (ESA) to treat symptomatic anaemia. Quality of Life will be assessed electronically with the aim of estimating improvement in quality of life for those patients receiving darbepoetin alfa (Aranesp®) who also have an increase in haemoglobin (Hb) of ≥1 g/dL
Detailed description
Before enrolling participants, each country was assigned to either cohort 1 (patients receiving only darbepoetin alfa) or cohort 2 (patients receiving any ESA). Cohort 2 was assigned only to those countries in which local regulations did not permit observational study participation by patients receiving a specific agent in a drug class.
Interventions
None listed
Sponsors
Amgen
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosed with breast, colorectal, ovarian, prostate, lung, bladder, endometrial, renal, pancreatic, esophageal or gastric cancer * Expected to receive at least 8 additional weeks of a given regimen of myelosuppressive chemotherapy after enrolment * Starting treatment with either darbepoetin alfa (in Cohort 1 countries) or any ESA (in Cohort 2 countries) as per European Summary of Product Characteristics (SPC) for symptomatic anaemia.
Exclusion criteria
* Received any ESA treatment or Red Blood Cell (RBC) transfusion within 28 days prior to enrolment * Known primary benign or malignant haematologic disorder which can cause anaemia * Known hypersensitivity to ESAs
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Receiving Darbepoetin Alfa With Improvement in Patient Perceived Fatigue (PPF) and Increase in Hemoglobin ≥ 1 g/dL | Baseline to Week 9 (Treatment Day 57). Due to the observational nature of the study and variation in ESA dosing schedules, assessments closest to day 57 and within Days 43 to 70 (inclusive) were used to calculate the Week 9 visit results. | Improvement in PPF was defined as improvement at Week 9 in Functional Assessment of Cancer Therapy-Fatigue (FACT-F) score of ≥ 3.5 points from Baseline (the minimally important difference \[MID\]), and an increase in hemoglobin was defined as ≥ 1 g/dL increase from Baseline. The FACT-F MID was determined by the mean FACT-F change score (between Baseline and Week 9) for participants who had an improvement in the fatigue visual analog scale (VAS) score of 5 ± 3 points. The FACT-F subscale consists of 13 fatigue-related items that are a subset of the Functional Assessment of Cancer Therapy - Anaemia (FACT-An) questionnaire. Participants indicate how they feel in response to 13 statements on a scale from 0 for Not at all to 4 for Very much. Total scores for the FACT-F subscale range from 0 to 52; the higher the score the better the quality of life. The fatigue-VAS is a 100-point scale, where fatigue-levels are rated from 0 (least fatigue) to 100 (worst possible fatigue). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants by Tumor Type With Improvement in Patient Perceived Fatigue (PPF) and Increase in Hemoglobin ≥ 1 g/dL | Baseline to Week 9 | Improvement in PPF was defined as improvement at week 9 in Functional Assessment of Cancer Therapy-Fatigue (FACT-F) score of ≥ 3.5 points from Baseline (the minimally important difference \[MID\]), and an increase in hemoglobin was defined as ≥ 1 g/dL increase from Baseline. The FACT-F MID was determined by the mean FACT-F change score (between Baseline and Week 9) for participants who had an improvement in the fatigue visual analog scale (VAS) score of 5 ± 3 points. The FACT-F subscale consists of 13 fatigue-related items that are a subset of the Functional Assessment of Cancer Therapy - Anaemia (FACT-An) questionnaire. Participants indicate how they feel in response to 13 statements on a scale from 0 for Not at all to 4 for Very much. Total scores for the FACT-F subscale range from 0 to 52; the higher the score the better the quality of life. The fatigue-VAS is a 100-point scale, where fatigue-levels are rated from 0 (least fatigue) to 100 (worst possible fatigue). |
| Mean Change From Baseline in FACT-F Score for Participants With a VAS Improvement of 5 ± 3 Points | Baseline and Week 9 | The FACT-F subscale consists of 13 fatigue-related items (statements) that are a subset of the Functional Assessment of Cancer Therapy - Anaemia (FACT-An) questionnaire. Participants are asked to indicate how they feel in response to each of the 13 statements on a scale from 0 for Not at all to 4 for Very much. Total scores for the FACT-F subscale can range from 0 to 52; the higher the score the better the quality of life. A positive change (\>0) from baseline score constitutes an improvement in fatigue between Baseline and Week 9. The fatigue-visual analog scale (VAS) is a 100-point scale where fatigue-levels are rated from 0 (least fatigue) to 100 (worst possible fatigue). |
| Time to First Increase in Hemoglobin | From Baseline until Week 9 | Time from Baseline to first increase in hemoglobin of ≥ 1 g/dL |
| Percentage of Participants With Improvement in Patient-perceived Fatigue (PPF) at Any Time | From Baseline to Week 13 | The percentage of participants with iimprovement in PPF at any time from Day 2 until the end-of-study assessment (Week 13). Improvement in PPF was defined as improvement in Functional Assessment of Cancer Therapy-Fatigue (FACT-F) score of ≥ 3.5 points from Baseline (the minimally important difference \[MID\]). The FACT-F MID was determined by the mean FACT-F change score (between Baseline and Week 9) for participants who had an improvement in the fatigue visual analog scale (VAS) score of 5 ± 3 points. The FACT-F subscale consists of 13 fatigue-related items that are a subset of the FACT-An questionnaire. Participants indicate how they feel in response to 13 statements on a scale from 0 for Not at all to 4 for Very much. Total scores for the FACT-F subscale range from 0 to 52; the higher the score the better the quality of life. The fatigue-VAS is a 100-point scale, where fatigue-levels are rated from 0 (least fatigue) to 100 (worst possible fatigue). |
| Percentage of Participants With Increase in Hemoglobin ≥ 1 g/dL at Any Time | From Baseline to Week 13 | The percentage of participants with increase in hemoglobin (≥ 1 g/dL) at any time from Day 2 until the end-of-study assessment (Week 13). |
Countries
Austria, Belgium, France, Germany, Greece, Italy, Netherlands, Poland, Romania
Participant flow
Recruitment details
Open to patients receiving systemic chemotherapy for solid tumors who also received darbepoetin alfa or another erythropoiesis-stimulating agent (ESA) to treat symptomatic anemia. First patient enrolled 10 october 2011; last patient enrolled 28 May 2013.
Pre-assignment details
Before enrolling participants, each country was assigned to either cohort 1 (patients receiving only darbepoetin alfa) or cohort 2 (patients receiving any ESA). Cohort 2 was assigned only to those countries in which local regulations did not permit observational study participation by participants receiving a specific agent in a drug class.
Participants by arm
| Arm | Count |
|---|---|
| Darbepoetin Alfa or Other ESA Participants receiving systemic chemotherapy for solid tumors who also received darbepoetin alfa (Aranesp®) or another erythropoiesis-stimulating agent (ESA) to treat symptomatic anemia according to routine institutional practice. | 1,158 |
| Total | 1,158 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 73 |
| Overall Study | Ineligibility determined | 23 |
| Overall Study | Lost to Follow-up | 37 |
| Overall Study | Not treated | 104 |
| Overall Study | Other | 18 |
| Overall Study | Physician Decision | 9 |
| Overall Study | Withdrawal by Subject | 21 |
Baseline characteristics
| Characteristic | Darbepoetin Alfa or Other ESA |
|---|---|
| Age, Continuous | 63.9 years STANDARD_DEVIATION 11.1 |
| Fatigue-Visual Analog Scale (VAS) Score | 51.2 units on a scale STANDARD_DEVIATION 22.6 |
| Functional Assessment of Cancer Therapy-Fatigue (FACT-F) score | 28.4 units on a scale STANDARD_DEVIATION 10.5 |
| Hemoglobin level | 9.3 g/dL STANDARD_DEVIATION 0.6 |
| Sex: Female, Male Female | 691 Participants |
| Sex: Female, Male Male | 467 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 8 / 1,158 |
| serious Total, serious adverse events | 2 / 1,158 |
Outcome results
Primary
Percentage of Participants Receiving Darbepoetin Alfa With Improvement in Patient Perceived Fatigue (PPF) and Increase in Hemoglobin ≥ 1 g/dL
Improvement in PPF was defined as improvement at Week 9 in Functional Assessment of Cancer Therapy-Fatigue (FACT-F) score of ≥ 3.5 points from Baseline (the minimally important difference \[MID\]), and an increase in hemoglobin was defined as ≥ 1 g/dL increase from Baseline. The FACT-F MID was determined by the mean FACT-F change score (between Baseline and Week 9) for participants who had an improvement in the fatigue visual analog scale (VAS) score of 5 ± 3 points. The FACT-F subscale consists of 13 fatigue-related items that are a subset of the Functional Assessment of Cancer Therapy - Anaemia (FACT-An) questionnaire. Participants indicate how they feel in response to 13 statements on a scale from 0 for Not at all to 4 for Very much. Total scores for the FACT-F subscale range from 0 to 52; the higher the score the better the quality of life. The fatigue-VAS is a 100-point scale, where fatigue-levels are rated from 0 (least fatigue) to 100 (worst possible fatigue).
Time frame: Baseline to Week 9 (Treatment Day 57). Due to the observational nature of the study and variation in ESA dosing schedules, assessments closest to day 57 and within Days 43 to 70 (inclusive) were used to calculate the Week 9 visit results.
Population: The Primary analysis set consists of enrolled participants who received at least 1 dose of darbepoetin alfa, have baseline assessments for each of Hemoglobin, FACT-F subscale and VAS, and analyzable post-baseline assessments for each of Hemoglobin, FACT-F subscale, and VAS at Week 9.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Darbepoetin Alfa | Percentage of Participants Receiving Darbepoetin Alfa With Improvement in Patient Perceived Fatigue (PPF) and Increase in Hemoglobin ≥ 1 g/dL | 31.8 percentage of participants |
Secondary
Mean Change From Baseline in FACT-F Score for Participants With a VAS Improvement of 5 ± 3 Points
The FACT-F subscale consists of 13 fatigue-related items (statements) that are a subset of the Functional Assessment of Cancer Therapy - Anaemia (FACT-An) questionnaire. Participants are asked to indicate how they feel in response to each of the 13 statements on a scale from 0 for Not at all to 4 for Very much. Total scores for the FACT-F subscale can range from 0 to 52; the higher the score the better the quality of life. A positive change (\>0) from baseline score constitutes an improvement in fatigue between Baseline and Week 9. The fatigue-visual analog scale (VAS) is a 100-point scale where fatigue-levels are rated from 0 (least fatigue) to 100 (worst possible fatigue).
Time frame: Baseline and Week 9
Population: Primary analysis set participants with a fatigue VAS score improvement at Week 9 of 5 ± 3 points from Baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Darbepoetin Alfa | Mean Change From Baseline in FACT-F Score for Participants With a VAS Improvement of 5 ± 3 Points | 3.5 units on a scale | Standard Deviation 5.5 |
Secondary
Percentage of Participants by Tumor Type With Improvement in Patient Perceived Fatigue (PPF) and Increase in Hemoglobin ≥ 1 g/dL
Improvement in PPF was defined as improvement at week 9 in Functional Assessment of Cancer Therapy-Fatigue (FACT-F) score of ≥ 3.5 points from Baseline (the minimally important difference \[MID\]), and an increase in hemoglobin was defined as ≥ 1 g/dL increase from Baseline. The FACT-F MID was determined by the mean FACT-F change score (between Baseline and Week 9) for participants who had an improvement in the fatigue visual analog scale (VAS) score of 5 ± 3 points. The FACT-F subscale consists of 13 fatigue-related items that are a subset of the Functional Assessment of Cancer Therapy - Anaemia (FACT-An) questionnaire. Participants indicate how they feel in response to 13 statements on a scale from 0 for Not at all to 4 for Very much. Total scores for the FACT-F subscale range from 0 to 52; the higher the score the better the quality of life. The fatigue-VAS is a 100-point scale, where fatigue-levels are rated from 0 (least fatigue) to 100 (worst possible fatigue).
Time frame: Baseline to Week 9
Population: Primary analysis set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Darbepoetin Alfa | Percentage of Participants by Tumor Type With Improvement in Patient Perceived Fatigue (PPF) and Increase in Hemoglobin ≥ 1 g/dL | Breast cancer (N=152) | 38.8 percentage of participants |
| Darbepoetin Alfa | Percentage of Participants by Tumor Type With Improvement in Patient Perceived Fatigue (PPF) and Increase in Hemoglobin ≥ 1 g/dL | Prostate cancer (N=39) | 28.2 percentage of participants |
| Darbepoetin Alfa | Percentage of Participants by Tumor Type With Improvement in Patient Perceived Fatigue (PPF) and Increase in Hemoglobin ≥ 1 g/dL | Small cell lung cancer (N=12) | 16.7 percentage of participants |
| Darbepoetin Alfa | Percentage of Participants by Tumor Type With Improvement in Patient Perceived Fatigue (PPF) and Increase in Hemoglobin ≥ 1 g/dL | Non-small cell lung cancer (N=70) | 28.6 percentage of participants |
| Darbepoetin Alfa | Percentage of Participants by Tumor Type With Improvement in Patient Perceived Fatigue (PPF) and Increase in Hemoglobin ≥ 1 g/dL | Colorectal cancer (N=71) | 31.0 percentage of participants |
| Darbepoetin Alfa | Percentage of Participants by Tumor Type With Improvement in Patient Perceived Fatigue (PPF) and Increase in Hemoglobin ≥ 1 g/dL | Ovarian cancer (N=79) | 38.0 percentage of participants |
| Darbepoetin Alfa | Percentage of Participants by Tumor Type With Improvement in Patient Perceived Fatigue (PPF) and Increase in Hemoglobin ≥ 1 g/dL | Bladder cancer (N=16) | 0.0 percentage of participants |
| Darbepoetin Alfa | Percentage of Participants by Tumor Type With Improvement in Patient Perceived Fatigue (PPF) and Increase in Hemoglobin ≥ 1 g/dL | Endometrial cancer (N=12) | 8.3 percentage of participants |
| Darbepoetin Alfa | Percentage of Participants by Tumor Type With Improvement in Patient Perceived Fatigue (PPF) and Increase in Hemoglobin ≥ 1 g/dL | Renal cancer (N=10) | 10.0 percentage of participants |
| Darbepoetin Alfa | Percentage of Participants by Tumor Type With Improvement in Patient Perceived Fatigue (PPF) and Increase in Hemoglobin ≥ 1 g/dL | Pancreatic cancer (N=31) | 35.5 percentage of participants |
| Darbepoetin Alfa | Percentage of Participants by Tumor Type With Improvement in Patient Perceived Fatigue (PPF) and Increase in Hemoglobin ≥ 1 g/dL | Esophogeal cancer (N=3) | 33.3 percentage of participants |
| Darbepoetin Alfa | Percentage of Participants by Tumor Type With Improvement in Patient Perceived Fatigue (PPF) and Increase in Hemoglobin ≥ 1 g/dL | Gastric cancer (N=15) | 26.7 percentage of participants |
Secondary
Percentage of Participants With Improvement in Patient-perceived Fatigue (PPF) at Any Time
The percentage of participants with iimprovement in PPF at any time from Day 2 until the end-of-study assessment (Week 13). Improvement in PPF was defined as improvement in Functional Assessment of Cancer Therapy-Fatigue (FACT-F) score of ≥ 3.5 points from Baseline (the minimally important difference \[MID\]). The FACT-F MID was determined by the mean FACT-F change score (between Baseline and Week 9) for participants who had an improvement in the fatigue visual analog scale (VAS) score of 5 ± 3 points. The FACT-F subscale consists of 13 fatigue-related items that are a subset of the FACT-An questionnaire. Participants indicate how they feel in response to 13 statements on a scale from 0 for Not at all to 4 for Very much. Total scores for the FACT-F subscale range from 0 to 52; the higher the score the better the quality of life. The fatigue-VAS is a 100-point scale, where fatigue-levels are rated from 0 (least fatigue) to 100 (worst possible fatigue).
Time frame: From Baseline to Week 13
Population: Primary analysis set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Darbepoetin Alfa | Percentage of Participants With Improvement in Patient-perceived Fatigue (PPF) at Any Time | 70.0 percentage of participants |
Secondary
Percentage of Participants With Increase in Hemoglobin ≥ 1 g/dL at Any Time
The percentage of participants with increase in hemoglobin (≥ 1 g/dL) at any time from Day 2 until the end-of-study assessment (Week 13).
Time frame: From Baseline to Week 13
Population: Primary analysis set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Darbepoetin Alfa | Percentage of Participants With Increase in Hemoglobin ≥ 1 g/dL at Any Time | 75.7 percentage of participants |
Secondary
Time to First Increase in Hemoglobin
Time from Baseline to first increase in hemoglobin of ≥ 1 g/dL
Time frame: From Baseline until Week 9
Population: Primary analysis set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Darbepoetin Alfa | Time to First Increase in Hemoglobin | 36.5 days |