Trial Outcomes & Findings for Anemia Treatment for Advanced Non-Small Cell Lung Cancer (NSCLC) Patients Receiving Chemotherapy (NCT NCT00858364)

Last Updated: 2022-11-30

Results Overview

Overall survival (OS) was defined as the time from randomization to the date of death due to any cause. Participants were censored on the date of last contact (ie, the date the participant was last known to be alive) if they were not known to have died.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

2549 participants

Primary outcome timeframe

From randomization until death or end of study; maximum time on follow-up was 93.6 months.

Results posted on

2022-11-30

Participant Flow

This study was conducted at 371 centers in Europe, Latin America, Asia, India, North America, Israel, and South Africa.

Eligible participants were randomized to darbepoetin alfa or placebo in a 2:1 ratio. Randomization was stratified by histology (squamous vs other), screening hemoglobin (\< 10.0 g/dL vs ≥ 10.0 g/dL), and geographic region.

Participant milestones

Participant milestones
Measure	Placebo Participants received placebo once every 3 weeks (Q3W) administered subcutaneously until 3 weeks after the completion of chemotherapy or upon determination of disease progression, whichever occurred first.	Darbepoetin Alfa Participants received darbepoetin alfa 500 µg once every 3 weeks (Q3W) administered subcutaneously until 3 weeks after the completion of chemotherapy or upon determination of disease progression, whichever occurred first.
Overall Study STARTED	846	1703
Overall Study Received Study Drug	837	1681
Overall Study COMPLETED	642	1246
Overall Study NOT COMPLETED	204	457

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Participants received placebo once every 3 weeks (Q3W) administered subcutaneously until 3 weeks after the completion of chemotherapy or upon determination of disease progression, whichever occurred first.	Darbepoetin Alfa Participants received darbepoetin alfa 500 µg once every 3 weeks (Q3W) administered subcutaneously until 3 weeks after the completion of chemotherapy or upon determination of disease progression, whichever occurred first.
Overall Study Administrative Decision	3	2
Overall Study Adverse Event	5	2
Overall Study Withdrawal by Subject	44	118
Overall Study Ineligibility Determined	1	10
Overall Study Lost to Follow-up	24	54
Overall Study Noncompliance	3	4
Overall Study Protocol Deviation	0	2
Overall Study Other	9	17
Overall Study Missing	1	1
Overall Study Still on-study	114	247

Baseline Characteristics

The primary analysis set includes all randomized and consented participants with non-small cell lung cancer who received at least one dose of study drug.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=846 Participants Participants received placebo once every 3 weeks (Q3W) administered subcutaneously until 3 weeks after the completion of chemotherapy or upon determination of disease progression, whichever occurred first.	Darbepoetin Alfa n=1703 Participants Participants received darbepoetin alfa 500 µg once every 3 weeks (Q3W) administered subcutaneously until 3 weeks after the completion of chemotherapy or upon determination of disease progression, whichever occurred first.	Total n=2549 Participants Total of all reporting groups
Age, Continuous	62.2 years STANDARD_DEVIATION 9.9 • n=846 Participants	61.6 years STANDARD_DEVIATION 9.8 • n=1703 Participants	61.8 years STANDARD_DEVIATION 9.8 • n=2549 Participants
Age, Customized 18 - 64 years	482 Participants n=846 Participants	1014 Participants n=1703 Participants	1496 Participants n=2549 Participants
Age, Customized 65 - 74 years	287 Participants n=846 Participants	547 Participants n=1703 Participants	834 Participants n=2549 Participants
Age, Customized 75 - 84 years	71 Participants n=846 Participants	134 Participants n=1703 Participants	205 Participants n=2549 Participants
Age, Customized ≥ 85 years	6 Participants n=846 Participants	8 Participants n=1703 Participants	14 Participants n=2549 Participants
Sex: Female, Male Female	281 Participants n=846 Participants	585 Participants n=1703 Participants	866 Participants n=2549 Participants
Sex: Female, Male Male	565 Participants n=846 Participants	1118 Participants n=1703 Participants	1683 Participants n=2549 Participants
Race/Ethnicity, Customized White or Caucasian	404 Participants n=846 Participants	808 Participants n=1703 Participants	1212 Participants n=2549 Participants
Race/Ethnicity, Customized Black or African American	27 Participants n=846 Participants	46 Participants n=1703 Participants	73 Participants n=2549 Participants
Race/Ethnicity, Customized Asian	357 Participants n=846 Participants	741 Participants n=1703 Participants	1098 Participants n=2549 Participants
Race/Ethnicity, Customized Japanese	7 Participants n=846 Participants	12 Participants n=1703 Participants	19 Participants n=2549 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	1 Participants n=846 Participants	0 Participants n=1703 Participants	1 Participants n=2549 Participants
Race/Ethnicity, Customized Aborigine	0 Participants n=846 Participants	1 Participants n=1703 Participants	1 Participants n=2549 Participants
Race/Ethnicity, Customized Other	5 Participants n=846 Participants	14 Participants n=1703 Participants	19 Participants n=2549 Participants
Race/Ethnicity, Customized Hispanic	45 Participants n=846 Participants	81 Participants n=1703 Participants	126 Participants n=2549 Participants
Geographic Region Western Europe, Israel and South Africa	54 Participants n=836 Participants • The primary analysis set includes all randomized and consented participants with non-small cell lung cancer who received at least one dose of study drug.	108 Participants n=1680 Participants • The primary analysis set includes all randomized and consented participants with non-small cell lung cancer who received at least one dose of study drug.	162 Participants n=2516 Participants • The primary analysis set includes all randomized and consented participants with non-small cell lung cancer who received at least one dose of study drug.
Geographic Region Central and Eastern Europe	220 Participants n=836 Participants • The primary analysis set includes all randomized and consented participants with non-small cell lung cancer who received at least one dose of study drug.	451 Participants n=1680 Participants • The primary analysis set includes all randomized and consented participants with non-small cell lung cancer who received at least one dose of study drug.	671 Participants n=2516 Participants • The primary analysis set includes all randomized and consented participants with non-small cell lung cancer who received at least one dose of study drug.
Geographic Region Latin America and Asia	166 Participants n=836 Participants • The primary analysis set includes all randomized and consented participants with non-small cell lung cancer who received at least one dose of study drug.	337 Participants n=1680 Participants • The primary analysis set includes all randomized and consented participants with non-small cell lung cancer who received at least one dose of study drug.	503 Participants n=2516 Participants • The primary analysis set includes all randomized and consented participants with non-small cell lung cancer who received at least one dose of study drug.
Geographic Region India	168 Participants n=836 Participants • The primary analysis set includes all randomized and consented participants with non-small cell lung cancer who received at least one dose of study drug.	339 Participants n=1680 Participants • The primary analysis set includes all randomized and consented participants with non-small cell lung cancer who received at least one dose of study drug.	507 Participants n=2516 Participants • The primary analysis set includes all randomized and consented participants with non-small cell lung cancer who received at least one dose of study drug.
Geographic Region North America	99 Participants n=836 Participants • The primary analysis set includes all randomized and consented participants with non-small cell lung cancer who received at least one dose of study drug.	192 Participants n=1680 Participants • The primary analysis set includes all randomized and consented participants with non-small cell lung cancer who received at least one dose of study drug.	291 Participants n=2516 Participants • The primary analysis set includes all randomized and consented participants with non-small cell lung cancer who received at least one dose of study drug.
Geographic Region China	123 Participants n=836 Participants • The primary analysis set includes all randomized and consented participants with non-small cell lung cancer who received at least one dose of study drug.	243 Participants n=1680 Participants • The primary analysis set includes all randomized and consented participants with non-small cell lung cancer who received at least one dose of study drug.	366 Participants n=2516 Participants • The primary analysis set includes all randomized and consented participants with non-small cell lung cancer who received at least one dose of study drug.
Geographic Region Japan	6 Participants n=836 Participants • The primary analysis set includes all randomized and consented participants with non-small cell lung cancer who received at least one dose of study drug.	10 Participants n=1680 Participants • The primary analysis set includes all randomized and consented participants with non-small cell lung cancer who received at least one dose of study drug.	16 Participants n=2516 Participants • The primary analysis set includes all randomized and consented participants with non-small cell lung cancer who received at least one dose of study drug.
Histology Squamous	289 Participants n=836 Participants • Primary analysis set	589 Participants n=1680 Participants • Primary analysis set	878 Participants n=2516 Participants • Primary analysis set
Histology Non-squamous	547 Participants n=836 Participants • Primary analysis set	1091 Participants n=1680 Participants • Primary analysis set	1638 Participants n=2516 Participants • Primary analysis set
Screening Hemoglobin < 10 g/dL	433 Participants n=836 Participants • Primary analysis set	870 Participants n=1680 Participants • Primary analysis set	1303 Participants n=2516 Participants • Primary analysis set
Screening Hemoglobin ≥ 10 g/dL	403 Participants n=836 Participants • Primary analysis set	810 Participants n=1680 Participants • Primary analysis set	1213 Participants n=2516 Participants • Primary analysis set

PRIMARY outcome

Timeframe: From randomization until death or end of study; maximum time on follow-up was 93.6 months.

Population: Primary analysis set (all randomized and consented participants with non-small cell lung cancer who received at least one dose of study drug)

Outcome measures

Outcome measures
Measure	Placebo n=836 Participants Participants received placebo once every 3 weeks (Q3W) administered subcutaneously until 3 weeks after the completion of chemotherapy or upon determination of disease progression, whichever occurred first.	Darbepoetin Alfa n=1680 Participants Participants received darbepoetin alfa 500 µg once every 3 weeks (Q3W) administered subcutaneously until 3 weeks after the completion of chemotherapy or upon determination of disease progression, whichever occurred first.
Overall Survival (OS)	9.260 months Interval 8.25 to 10.02	9.460 months Interval 8.9 to 10.12

SECONDARY outcome

Timeframe: From randomization until disease progression or death; maximum time on follow-up was 87.23 months.

Population: The radiographic endpoint primary analysis set includes all participants in the primary analysis set who did not have disease progression prior to randomization.

Progression-free survival was defined as the time from randomization to the date of radiographic disease progression or death from any cause, whichever event occurred first. Participants without either event were censored on the date of their last disease assessment. Disease progression was based on the investigator's assessment of scans using the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0 or 1.1 depending on the timing of enrollment.

Outcome measures

Outcome measures
Measure	Placebo n=819 Participants Participants received placebo once every 3 weeks (Q3W) administered subcutaneously until 3 weeks after the completion of chemotherapy or upon determination of disease progression, whichever occurred first.	Darbepoetin Alfa n=1638 Participants Participants received darbepoetin alfa 500 µg once every 3 weeks (Q3W) administered subcutaneously until 3 weeks after the completion of chemotherapy or upon determination of disease progression, whichever occurred first.
Progression-free Survival (PFS)	4.340 months Interval 4.17 to 4.7	4.800 months Interval 4.37 to 5.32

SECONDARY outcome

Timeframe: Week 5 (day 29) to end of the efficacy treatment period (EOETP; defined as 21 days after either the last dose of study drug or the last dose of chemotherapy, whichever was later); median (range) duration of dosing was 10 (1 to 106) weeks in both groups.

Population: Primary analysis set participants who were on study as of day 29

Any red blood cell (RBC) transfusion (packed RBCs or whole blood) given or a hemoglobin ≤ 8.0 g/dL on or after study day 29 until the EOETP, inclusive.

Outcome measures

Outcome measures
Measure	Placebo n=764 Participants Participants received placebo once every 3 weeks (Q3W) administered subcutaneously until 3 weeks after the completion of chemotherapy or upon determination of disease progression, whichever occurred first.	Darbepoetin Alfa n=1517 Participants Participants received darbepoetin alfa 500 µg once every 3 weeks (Q3W) administered subcutaneously until 3 weeks after the completion of chemotherapy or upon determination of disease progression, whichever occurred first.
Percentage of Participants With a Red Blood Cell Transfusion or Hemoglobin ≤ 8.0 g/dL From Week 5 to End of the Efficacy Treatment Period	29.2 percentage of participants	22.5 percentage of participants

SECONDARY outcome

Timeframe: From first dose of study drug until 30 days after last dose; the median (range) duration of treatment was 10 (1 to 106) weeks in both groups.

Population: All randomized and consented participants who received at least 1 dose of study drug. Four participants in the placebo group received at least 1 dose of darbepoetin alfa during the study and were included in the darbepoetin alfa group for safety analyses.

Adverse events of interest for darbepoetin alfa, based on clinical data in anemic patients with cancer to date, included the following categories: antibody-mediated pure red cell aplasia (PRCA), cardiac failure, central nervous system vascular disorders, convulsions, embolic and thrombotic events, hypersensitivity, hypertension, ischemic heart disease, malignancies, and severe cutaneous adverse reactions. Lack of efficacy and medication errors were also evaluated.

Outcome measures

Outcome measures
Measure	Placebo n=833 Participants Participants received placebo once every 3 weeks (Q3W) administered subcutaneously until 3 weeks after the completion of chemotherapy or upon determination of disease progression, whichever occurred first.	Darbepoetin Alfa n=1685 Participants Participants received darbepoetin alfa 500 µg once every 3 weeks (Q3W) administered subcutaneously until 3 weeks after the completion of chemotherapy or upon determination of disease progression, whichever occurred first.
Number of Participants With Adverse Events of Special Interest Central nervous system vascular disorders	8 Participants	25 Participants
Number of Participants With Adverse Events of Special Interest Convulsions	8 Participants	9 Participants
Number of Participants With Adverse Events of Special Interest Embolic and thrombotic events, venous	23 Participants	51 Participants
Number of Participants With Adverse Events of Special Interest Embolic and thrombotic events, unspecified/mixed	10 Participants	26 Participants
Number of Participants With Adverse Events of Special Interest Severe cutaneous adverse reactions	11 Participants	35 Participants
Number of Participants With Adverse Events of Special Interest Any adverse events of interest	157 Participants	369 Participants
Number of Participants With Adverse Events of Special Interest Antibody-mediated pure red cell aplasia	20 Participants	51 Participants
Number of Participants With Adverse Events of Special Interest Cardiac failure	7 Participants	12 Participants
Number of Participants With Adverse Events of Special Interest Embolic and thrombotic events	34 Participants	89 Participants
Number of Participants With Adverse Events of Special Interest Embolic and thrombotic events, arterial	6 Participants	19 Participants
Number of Participants With Adverse Events of Special Interest Hypersensitivity	75 Participants	178 Participants
Number of Participants With Adverse Events of Special Interest Hypertension	26 Participants	41 Participants
Number of Participants With Adverse Events of Special Interest Ischaemic heart disease	9 Participants	23 Participants
Number of Participants With Adverse Events of Special Interest Lack of efficacy/effect	0 Participants	0 Participants
Number of Participants With Adverse Events of Special Interest Malignancies	16 Participants	38 Participants
Number of Participants With Adverse Events of Special Interest Medication errors	0 Participants	1 Participants

SECONDARY outcome

Timeframe: Day 1 to end of the efficacy treatment period (EOETP; defined as 21 days after either the last dose of study drug or the last dose of chemotherapy, whichever was later); median (range) duration of dosing was 10 (1 to 106) weeks in both groups.

Population: The radiographic endpoint primary analysis set includes all participants in the primary analysis set who did not have disease progression prior to randomization.

Objective response was defined as the incidence of a complete or partial response at any time during the study. Response was determined by the investigator's assessment of the scans using RECIST version 1.0 or 1.1 depending on the timing of enrollment.

Outcome measures

Outcome measures
Measure	Placebo n=819 Participants Participants received placebo once every 3 weeks (Q3W) administered subcutaneously until 3 weeks after the completion of chemotherapy or upon determination of disease progression, whichever occurred first.	Darbepoetin Alfa n=1638 Participants Participants received darbepoetin alfa 500 µg once every 3 weeks (Q3W) administered subcutaneously until 3 weeks after the completion of chemotherapy or upon determination of disease progression, whichever occurred first.
Percentage of Participants With an Objective Tumor Response	32.6 percentage of participants	36.2 percentage of participants

SECONDARY outcome

Timeframe: Baseline and end of the efficacy treatment period (EOETP; defined as 21 days after either the last dose of study drug or the last dose of chemotherapy, whichever was later. the median (range) duration of treatment was 10 (1 to 106) weeks in both groups.

Population: Randomized and consented participants who received at least one dose of study drug and with a postbaseline result.

Developing antibody incidence was defined as neutralizing antibody positive postbaseline with a negative or no result at baseline.

Outcome measures

Outcome measures
Measure	Placebo n=803 Participants Participants received placebo once every 3 weeks (Q3W) administered subcutaneously until 3 weeks after the completion of chemotherapy or upon determination of disease progression, whichever occurred first.	Darbepoetin Alfa n=1606 Participants Participants received darbepoetin alfa 500 µg once every 3 weeks (Q3W) administered subcutaneously until 3 weeks after the completion of chemotherapy or upon determination of disease progression, whichever occurred first.
Number of Participants Who Developed Neutralizing Antibodies to Darbepoetin Alfa	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Week 1 to end of the efficacy treatment period (EOETP; defined as 21 days after either the last dose of study drug or the last dose of chemotherapy, whichever was later); the median (range) duration of treatment was 10 (1 to 106) weeks in both groups.

Population: Primary analysis set

Any red blood cell (RBC) transfusion (packed RBCs or whole blood) given or a hemoglobin ≤ 8.0 g/dL on or after study day 1 until the EOETP, inclusive.

Outcome measures

Outcome measures
Measure	Placebo n=836 Participants Participants received placebo once every 3 weeks (Q3W) administered subcutaneously until 3 weeks after the completion of chemotherapy or upon determination of disease progression, whichever occurred first.	Darbepoetin Alfa n=1680 Participants Participants received darbepoetin alfa 500 µg once every 3 weeks (Q3W) administered subcutaneously until 3 weeks after the completion of chemotherapy or upon determination of disease progression, whichever occurred first.
Percentage of Participants With a Red Blood Cell Transfusion or Hemoglobin ≤ 8.0 g/dL From Week 1 to End of the Efficacy Treatment Period	29.7 percentage of participants	24.2 percentage of participants

SECONDARY outcome

Timeframe: Baseline and end of the efficacy treatment period (EOETP; defined as 21 days after either the last dose of study drug or the last dose of chemotherapy, whichever was later); the median (range) duration of treatment was 10 (1 to 106) weeks in both groups.

Population: Primary analysis set with available baseline and at least 1 postbaseline value; if the EOETP value was missing, the last available postbaseline value was used.

Post-baseline hemoglobin values within 28 days after a RBC transfusion were not be used in the calculation of change.

Outcome measures

Outcome measures
Measure	Placebo n=633 Participants Participants received placebo once every 3 weeks (Q3W) administered subcutaneously until 3 weeks after the completion of chemotherapy or upon determination of disease progression, whichever occurred first.	Darbepoetin Alfa n=1344 Participants Participants received darbepoetin alfa 500 µg once every 3 weeks (Q3W) administered subcutaneously until 3 weeks after the completion of chemotherapy or upon determination of disease progression, whichever occurred first.
Change From Baseline in Hemoglobin to End of Efficacy Treatment Period	-0.11 g/dL Standard Deviation 1.71	0.50 g/dL Standard Deviation 1.81

Adverse Events

Placebo

Serious events: 259 serious events

Other events: 674 other events

Deaths: 657 deaths

Darbepoetin Alfa

Serious events: 524 serious events

Other events: 1319 other events

Deaths: 1273 deaths

Serious adverse events

Other adverse events

Additional Information

Study Director

Amgen Inc.

Phone: 866-572-6436

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results after completion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.
Publication restrictions are in place

Restriction type: OTHER