Phase 3 Study With Carfilzomib and Dexamethasone Versus Bortezomib and Dexamethasone for Relapsed Multiple Myeloma Patients (ENDEAVOR)

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ClinicalTrials.gov Identifier: NCT01568866

Recruitment Status : Completed

First Posted : April 2, 2012

Results First Posted : December 11, 2015

Last Update Posted : November 14, 2022

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Sponsor:

Information provided by (Responsible Party):

Amgen

Study Type	Interventional
Study Design	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition	Multiple Myeloma
Interventions	Drug: Carfilzomib Drug: Bortezomib Drug: Dexamethasone
Enrollment	929

Participant Flow

Recruitment Details

Adults with relapsed multiple myeloma were enrolled between 20 June 2012 and 30 June 2014 at 198 centers in 27 countries in Europe, North America, South America, and the Asia-Pacific region.

Results are reported as of the data cut-off date of 03 January 2017, the pre-specified 2nd interim analysis of the secondary endpoint of overall survival.

Pre-assignment Details

Randomization was stratified by previous proteasome inhibitor therapy (yes vs no), previous lines of treatment (1 vs 2 or 3), International Staging System stage (I vs II-III), and planned route of bortezomib administration (intravenous vs subcutaneous) if randomly assigned to the bortezomib group.


Arm/Group Title	Bortezomib + DEX	Carfilzomib + DEX
Arm/Group Description	Participants received bortezomib 1....	Participants received 20 mg/m² carf...
Arm/Group Description	Participants received bortezomib 1.3 mg/m² administered intravenously (IV) or subcutaneously (SC) on Days 1, 4, 8, and 11 of a 21-day cycle plus dexamethasone (DEX) 20 mg administered on Days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle.	Participants received 20 mg/m² carfilzomib administered by IV infusion on Days 1 and 2 of Cycle 1, followed by 56 mg/m² on Days 8, 9, 15, and 16 of Cycle 1 and for each 28-day cycle thereafter. Additionally, participants received 20 mg dexamethasone on Days 1, 2, 8, 9, 15, 16, 22, and 23 of each 28 day cycle.
Period Title: Overall Study
Started	465	464
Received Treatment	456	463
Completed	27 ^[1]	48 ^[1]
Not Completed	438	416
Reason Not Completed
Disease Progression	208	183
Adverse Event	94	96
Patient Request	55	71
Physician Decision	40	32
Withdrawal by Subject	19	11
Death	10	18
Protocol Non-compliance	2	4
Lost to Follow-up	1	0
Randomized but Not Dosed	9	1
[1] Indicates participants still receiving treatment

Baseline Characteristics

Arm/Group Title		Bortezomib + DEX	Carfilzomib + DEX	Total
Arm/Group Description		Participants received bortezomib 1....	Participants received 20 mg/m² carf...	Total of all reporting groups
Arm/Group Description		Participants received bortezomib 1.3 mg/m² administered intravenously (IV) or subcutaneously (SC) on Days 1, 4, 8, and 11 of a 21-day cycle plus dexamethasone (DEX) 20 mg administered on Days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle.	Participants received 20 mg/m² carfilzomib administered by IV infusion on Days 1 and 2 of Cycle 1, followed by 56 mg/m² on Days 8, 9, 15, and 16 of Cycle 1 and for each 28-day cycle thereafter. Additionally, participants received 20 mg dexamethasone on Days 1, 2, 8, 9, 15, 16, 22, and 23 of each 28 day cycle.	Total of all reporting groups
Overall Number of Baseline Participants		465	464	929
Baseline Analysis Population Description		...
Baseline Analysis Population Description		Intent-to-treat population (all randomized participants)
Age, Continuous Median (Full Range) Unit of measure: Years
	Number Analyzed	465 participants	464 participants	929 participants
		65.0 (30.0 to 88.0)	65.0 (35.0 to 89.0)	65.0 (30.0 to 89.0)
Age, Customized Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	465 participants	464 participants	929 participants
	< 65 years	210 45.2%	223 48.1%	433 46.6%
	65 -74 years	189 40.6%	164 35.3%	353 38.0%
	≥ 75 years	66 14.2%	77 16.6%	143 15.4%
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	465 participants	464 participants	929 participants
	Female	236 50.8%	224 48.3%	460 49.5%
	Male	229 49.2%	240 51.7%	469 50.5%
Race/Ethnicity, Customized Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	465 participants	464 participants	929 participants
	White	353 75.9%	348 75.0%	701 75.5%
	Black	9 1.9%	8 1.7%	17 1.8%
	Asian	57 12.3%	56 12.1%	113 12.2%
	Native Hawaiian/Other Pacific Islander	0 0.0%	2 0.4%	2 0.2%
	Not Reported	45 9.7%	50 10.8%	95 10.2%
	Multiple	1 0.2%	0 0.0%	1 0.1%
Eastern Cooperative Oncology Group (ECOG) Performance Status ^[1] Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	465 participants	464 participants	929 participants
	0 (Fully active)	232 49.9%	221 47.6%	453 48.8%
	1 (Restrictive but ambulatory)	203 43.7%	211 45.5%	414 44.6%
	2 (Ambulatory but unable to work)	30 6.5%	32 6.9%	62 6.7%
		[1] Measure Description: Eastern Cooperative Oncology Group (ECOG) Performance Status is used by doctors and researchers to assess how a participants disease is progressing, assess how the disease affects the daily living activities of the participant and determine appropriate treatment and prognosis. 0 = Fully Active; 1 = Restricted activity but ambulatory; 2 = Ambulatory but unable to carry out work activities; 3 = Limited Self-Care; 4 = Completely Disabled, no self-care, confined to bed or chair; 5 = Dead.
Stratification Factor: Prior Proteasome Inhibitor Treatment Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	465 participants	464 participants	929 participants
	Carfilzomib or bortezomib	253 54.4%	252 54.3%	505 54.4%
	No prior carfilzomib or bortezomib	212 45.6%	212 45.7%	424 45.6%
Stratification Factor: Lines of Prior Treatment Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	465 participants	464 participants	929 participants
	1 line	229 49.2%	231 49.8%	460 49.5%
	2 or 3 lines	236 50.8%	233 50.2%	469 50.5%
Stratification Factor: International Staging System (ISS) Stage ^[1] Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	465 participants	464 participants	929 participants
	Stage I	204 43.9%	205 44.2%	409 44.0%
	Stage II or III	261 56.1%	259 55.8%	520 56.0%
		[1] Measure Description: The International Staging System (ISS) for myeloma was published by the International Myeloma Working Group: Stage I: β2-microglobulin (β2M) < 3.5 mg/L, albumin >= 3.5 g/dL Stage II: β2M < 3.5 mg/L and albumin < 3.5 g/dL; or β2M 3.5 mg/L - 5.5 mg/L irrespective of the serum albumin Stage III: β2M ≥ 5.5 mg/L
Stratification Factor: Route of Bortezomib Administration ^[1] Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	465 participants	464 participants	929 participants
	Intravenous	108 23.2%	108 23.3%	216 23.3%
	Subcutaneous	357 76.8%	356 76.7%	713 76.7%
		[1] Measure Description: The route of bortezomib administration (IV versus SC) was made in accordance with local regulatory approved route of administration. The value for this variable was selected for all participants prior to randomization to treatment group in order to balance the baseline characteristics that led to the choice of the particular route of bortezomib administration between the 2 arms.

Outcome Measures

1.Primary Outcome


Title	Progression-free Survival
Description	Progression-free survival (PFS) was defined as the time from randomiza...
Description	Progression-free survival (PFS) was defined as the time from randomization to the earlier of disease progression or death due to any cause. Participants were evaluated for disease response and progression according to the International Myeloma Working Group-Uniform Response Criteria (IMWG-URC) as assessed by an Independent Review Committee (IRC). Median PFS was estimated using the Kaplan-Meier method. Participants with no baseline disease assessments, starting a new anticancer therapy before documentation of disease progression or death, death or disease progression immediately after more than 1 consecutively missed disease assessment visit, or alive without documentation of disease progression before the data cut-off date were censored.
Time Frame	From randomization until the data cut-off date of 10 November 2014; median follow-up time for PFS was 11.1.and 11.9 months in the bortezomib and carfilzomib arms respectively

Outcome Measure Data

Analysis Population Description

Intent-to-treat population


Arm/Group Title	Bortezomib + DEX	Carfilzomib + DEX
Arm/Group Description:	Participants received bortezomib 1....	Participants received 20 mg/m² carf...
Arm/Group Description:	Participants received bortezomib 1.3 mg/m² administered intravenously (IV) or subcutaneously (SC) on Days 1, 4, 8, and 11 of a 21-day cycle plus dexamethasone (DEX) 20 mg administered on Days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle.	Participants received 20 mg/m² carfilzomib administered by IV infusion on Days 1 and 2 of Cycle 1, followed by 56 mg/m² on Days 8, 9, 15, and 16 of Cycle 1 and for each 28-day cycle thereafter. Additionally, participants received 20 mg dexamethasone on Days 1, 2, 8, 9, 15, 16, 22, and 23 of each 28 day cycle.
Overall Number of Participants Analyzed	465	464
Median (95% Confidence Interval) Unit of Measure: months
	9.4 (8.4 to 10.4)	18.7 ^[1] (15.6 to NA)

[1]

Could not be estimated due to the low number of events.

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Bortezomib + DEX, Carfilzomib + DEX
	Comments	The PFS interim analysis was to be performed using a group sequential monitoring plan. The monitoring plan included an O'Brien-Fleming type of efficacy stopping boundary constructed using the Lan-DeMets alpha spending function to ensure a 1-sided Type I error rate ≤ 0.025.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	< 0.0001
	Comments	[Not Specified]
	Method	Stratified Log Rank
	Comments	Log rank test stratified by the randomization stratification factors.

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.533
	Confidence Interval	(2-Sided) 95% 0.437 to 0.651
	Estimation Comments	The hazard ratio (carfilzomib/bortezomib) was estimated using a Cox proportional hazards model stratified by prior proteasome inhibitor treatment, lines of prior treatment, ISS stage, and choice of route of bortezomib administration.

2.Secondary Outcome


Title	Overall Survival
Description	Overall survival (OS) is defined as the time from randomization to the...
Description	Overall survival (OS) is defined as the time from randomization to the date of death (whatever the cause). Participants who were alive or lost to follow-up as of the data analysis cut-off date were censored at the patient's date of last contact (last known to be alive). Median overall survival was estimated using the Kaplan-Meier method.
Time Frame	From randomization until the data cut-off date of 03 January 2017; median follow-up time for OS was 36.9 and 37.5 months for each treatment group respectively.

Outcome Measure Data

Analysis Population Description

Intent-to-treat population


Arm/Group Title	Bortezomib + DEX	Carfilzomib + DEX
Arm/Group Description:	Participants received bortezomib 1....	Participants received 20 mg/m² carf...
Arm/Group Description:	Participants received bortezomib 1.3 mg/m² administered intravenously (IV) or subcutaneously (SC) on Days 1, 4, 8, and 11 of a 21-day cycle plus dexamethasone (DEX) 20 mg administered on Days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle.	Participants received 20 mg/m² carfilzomib administered by IV infusion on Days 1 and 2 of Cycle 1, followed by 56 mg/m² on Days 8, 9, 15, and 16 of Cycle 1 and for each 28-day cycle thereafter. Additionally, participants received 20 mg dexamethasone on Days 1, 2, 8, 9, 15, 16, 22, and 23 of each 28 day cycle.
Overall Number of Participants Analyzed	465	464
Median (95% Confidence Interval) Unit of Measure: months
	40.0 (32.6 to 42.3)	47.6 ^[1] (42.5 to NA)

[1]

Could not be estimated due to the low number of events

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Bortezomib + DEX, Carfilzomib + DEX
	Comments	The second interim analysis of overall survival was to be conducted after 394 events had been reached. A one-sided significance level was determined using the O'Brien-Fleming-type α spending function based on the actual number of events (α=0.0123).
	Type of Statistical Test	Superiority or Other (legacy)
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.0100
	Comments	The multiplicity in testing secondary endpoints was adjusted per group using the sequential Holm procedure to preserve the family-wise error rate at 0.025.
	Method	Stratified Log Rank
	Comments	Log rank test stratified by the randomization stratification factors.

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.791
	Confidence Interval	(2-Sided) 95% 0.648 to 0.964
	Estimation Comments	The hazard ratio (carfilzomib/bortezomib) was estimated using a Cox proportional hazards model stratified by prior proteasome inhibitor treatment, lines of prior treatment, ISS stage, and choice of route of bortezomib administration.

3.Secondary Outcome


Title	Overall Response
Description	Disease response was evaluated according to the IMWG-URC by the IRC. O...
Description	Disease response was evaluated according to the IMWG-URC by the IRC. Overall response was defined as the percentage of participants with a best overall response of partial response (PR), very good PR (VGPR), complete response (CR) or stringent CR (sCR). sCR: As for CR, normal serum free light chain (SFLC) ratio and no clonal cells in bone marrow (BM). CR: No immunofixation on serum and urine, disappearance of any soft tissue plasmacytomas and < 5% plasma cells in BM biopsy; VGPR: Serum and urine M-protein detectable by immunofixation but not electrophoresis or ≥ 90% reduction in serum M-protein with urine M-protein <100 mg/24 hours. A ≥ 50% reduction in the size of soft tissue plasmacytomas if present at baseline. PR: ≥ 50% reduction of serum M-protein and reduction in urine M-protein by ≥ 90% or to < 200 mg/24 hours. A ≥ 50% reduction in the size of soft tissue plasmacytomas if present at baseline.
Time Frame	Disease response was assessed every 28 days until end of treatment or the data cut-off date of 10 November 2014; median duration of treatment was 27 weeks in the bortezomib group and 40 weeks in the carfilzomib treatment group.

Outcome Measure Data

Analysis Population Description

Intent-to-treat population


Arm/Group Title	Bortezomib + DEX	Carfilzomib + DEX
Arm/Group Description:	Participants received bortezomib 1....	Participants received 20 mg/m² carf...
Arm/Group Description:	Participants received bortezomib 1.3 mg/m² administered intravenously (IV) or subcutaneously (SC) on Days 1, 4, 8, and 11 of a 21-day cycle plus dexamethasone (DEX) 20 mg administered on Days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle.	Participants received 20 mg/m² carfilzomib administered by IV infusion on Days 1 and 2 of Cycle 1, followed by 56 mg/m² on Days 8, 9, 15, and 16 of Cycle 1 and for each 28-day cycle thereafter. Additionally, participants received 20 mg dexamethasone on Days 1, 2, 8, 9, 15, 16, 22, and 23 of each 28 day cycle.
Overall Number of Participants Analyzed	465	464
Measure Type: Number Number (95% Confidence Interval) Unit of Measure: percentage of participants
	62.6 (58.0 to 67.0)	76.9 (72.8 to 80.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Bortezomib + DEX, Carfilzomib + DEX
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other (legacy)
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	< 0.0001
	Comments	The multiplicity in testing secondary endpoints was adjusted per group using the sequential Holm procedure to preserve the family-wise error rate at 0.025.
	Method	Stratified Cochran-Mantel-Haenszel
	Comments	Cochran-Mantel-Haenszel test stratified by the randomization stratification factors.

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.032
	Confidence Interval	(2-Sided) 95% 1.519 to 2.718
	Estimation Comments	The odds ratio (carfilzomib/bortezomib) was calculated using the Cochran-Mantel-Haenszel method stratified by prior proteasome inhibitor treatment, lines of prior treatment, ISS stage, and choice of route of bortezomib administration.

4.Secondary Outcome


Title	Duration of Response
Description	Duration of response (DOR) was calculated for participants who achieve...
Description	Duration of response (DOR) was calculated for participants who achieved an sCR, CR, VGPR, or PR. Duration of response is defined as the time from first evidence of PR or better to confirmation of disease progression or death due to any cause. Median duration of response was estimated using the Kaplan-Meier method. Participants with no baseline disease assessments, starting a new anticancer therapy before documentation of disease progression or death, death or disease progression immediately after more than 1 consecutively missed disease assessment visit, or alive without documentation of disease progression before the data cut-off date were censored.
Time Frame	From randomization until the data cut-off date of 10 November 2014; median follow-up time for DOR was 9.4 and 10.4 months for each treatment group respectively.

Outcome Measure Data

Analysis Population Description

Intent-to-treat population with an overall response


Arm/Group Title	Bortezomib + DEX	Carfilzomib + DEX
Arm/Group Description:	Participants received bortezomib 1....	Participants received 20 mg/m² carf...
Arm/Group Description:	Participants received bortezomib 1.3 mg/m² administered intravenously (IV) or subcutaneously (SC) on Days 1, 4, 8, and 11 of a 21-day cycle plus dexamethasone (DEX) 20 mg administered on Days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle.	Participants received 20 mg/m² carfilzomib administered by IV infusion on Days 1 and 2 of Cycle 1, followed by 56 mg/m² on Days 8, 9, 15, and 16 of Cycle 1 and for each 28-day cycle thereafter. Additionally, participants received 20 mg dexamethasone on Days 1, 2, 8, 9, 15, 16, 22, and 23 of each 28 day cycle.
Overall Number of Participants Analyzed	291	357
Median (95% Confidence Interval) Unit of Measure: months
	10.4 (9.3 to 13.8)	21.3 ^[1] (21.3 to NA)

[1]

Could not be estimated due to the low number of events

5.Secondary Outcome


Title	Percentage of Participants With ≥ Grade 2 Peripheral Neuropathy
Description	Neuropathy events were defined as Grade 2 or higher peripheral neuropa...
Description	Neuropathy events were defined as Grade 2 or higher peripheral neuropathy as specified by peripheral neuropathy Standardised Medical Dictionary for Regulatory Activities (MedDRA) Query, narrow (scope) (SMQN) terms. Peripheral neuropathy was assessed by neurologic exam and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03: Grade 1: Asymptomatic; Grade 2: Moderate symptoms, limiting instrumental activities of daily living (ADL) Grade 3: Severe symptoms; limiting self-care ADL; Grade 4: Life-threatening consequences, urgent intervention indicated; Grade 5: Death.
Time Frame	From the first dose of study drug up to 30 days after the last dose of study drug as of the data cut-off date of 10 November 2014; median duration of treatment was 27 weeks in the bortezomib group and 40 weeks in the carfilzomib treatment group.

Outcome Measure Data

Analysis Population Description

Safety population (all participants who received at least 1 dose of study treatment)


Arm/Group Title	Bortezomib + DEX	Carfilzomib + DEX
Arm/Group Description:	Participants received bortezomib 1....	Participants received 20 mg/m² carf...
Arm/Group Description:	Participants received bortezomib 1.3 mg/m² administered intravenously (IV) or subcutaneously (SC) on Days 1, 4, 8, and 11 of a 21-day cycle plus dexamethasone (DEX) 20 mg administered on Days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle.	Participants received 20 mg/m² carfilzomib administered by IV infusion on Days 1 and 2 of Cycle 1, followed by 56 mg/m² on Days 8, 9, 15, and 16 of Cycle 1 and for each 28-day cycle thereafter. Additionally, participants received 20 mg dexamethasone on Days 1, 2, 8, 9, 15, 16, 22, and 23 of each 28 day cycle.
Overall Number of Participants Analyzed	456	463
Measure Type: Number Number (95% Confidence Interval) Unit of Measure: percentage of participants
	32.0 (27.7 to 36.3)	6.0 (3.9 to 8.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Bortezomib + DEX, Carfilzomib + DEX
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other (legacy)
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	The multiplicity in testing secondary endpoints was adjusted per group using the sequential Holm procedure to preserve the family-wise error rate at 0.025.
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.137
	Confidence Interval	(2-Sided) 95% 0.089 to 0.210
	Estimation Comments	The odds ratio (carfilzomib/bortezomib) was estimated using the unconditional Cochran-Mantel-Haenszel method.

6.Secondary Outcome


Title	Percentage of Participants With a Significant Reduction in Left Ventricular Ejection Fraction (LVEF)
Description	A significant reduction in LVEF was defined as a ≥ 10% decrease ...
Description	A significant reduction in LVEF was defined as a ≥ 10% decrease (absolute change) from baseline in participants whose baseline LVEF is ≤ 55%. For participants with LVEF > 55% at baseline, a significant change was defined as a decrease in LVEF to < 45%.
Time Frame	Baseline and 24 weeks

Outcome Measure Data

Analysis Population Description

Cardiopulmonary Safety Evaluable subgroup (all randomized participants who enrolled in the cardiopulmonary substudy with evaluable baseline echocardiogram scans per the central laboratory) and with both baseline and at least one post-baseline LVEF measurement within 24 weeks.


Arm/Group Title	Bortezomib + DEX	Carfilzomib + DEX
Arm/Group Description:	Participants received bortezomib 1....	Participants received 20 mg/m² carf...
Arm/Group Description:	Participants received bortezomib 1.3 mg/m² administered intravenously (IV) or subcutaneously (SC) on Days 1, 4, 8, and 11 of a 21-day cycle plus dexamethasone (DEX) 20 mg administered on Days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle.	Participants received 20 mg/m² carfilzomib administered by IV infusion on Days 1 and 2 of Cycle 1, followed by 56 mg/m² on Days 8, 9, 15, and 16 of Cycle 1 and for each 28-day cycle thereafter. Additionally, participants received 20 mg dexamethasone on Days 1, 2, 8, 9, 15, 16, 22, and 23 of each 28 day cycle.
Overall Number of Participants Analyzed	40	48
Measure Type: Number Unit of Measure: percentage of participants
	2.6	0.0

7.Secondary Outcome


Title	Change From Baseline in Right Ventricular Fractional Area Change (FAC)
Description	Right ventricular function was assessed by measuring fractional area c...
Description	Right ventricular function was assessed by measuring fractional area change (FAC) on echocardiogram.
Time Frame	Baseline and Weeks 12, 24 and 36 and at end of treatment (median duration of treatment was 27 weeks in the bortezomib group and 40 weeks in the carfilzomib treatment group).

Outcome Measure Data

Analysis Population Description

Cardiopulmonary Safety Evaluable subgroup with available FAC data at baseline; "n" indicates participants whose results were available at both the baseline and the specified post-baseline visit.


Arm/Group Title	Bortezomib + DEX	Carfilzomib + DEX
Arm/Group Description:	Participants received bortezomib 1....	Participants received 20 mg/m² carf...
Arm/Group Description:	Participants received bortezomib 1.3 mg/m² administered intravenously (IV) or subcutaneously (SC) on Days 1, 4, 8, and 11 of a 21-day cycle plus dexamethasone (DEX) 20 mg administered on Days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle.	Participants received 20 mg/m² carfilzomib administered by IV infusion on Days 1 and 2 of Cycle 1, followed by 56 mg/m² on Days 8, 9, 15, and 16 of Cycle 1 and for each 28-day cycle thereafter. Additionally, participants received 20 mg dexamethasone on Days 1, 2, 8, 9, 15, 16, 22, and 23 of each 28 day cycle.
Overall Number of Participants Analyzed	52	55
Mean (Standard Deviation) Unit of Measure: percent fractional area change
Week 12 (n=40, 40)	-0.7 (5.00)	-1.1 (5.36)
Week 24 (n=26, 31)	0.7 (6.10)	-1.0 (5.03)
Week 36 (n=15, 18)	-0.5 (7.27)	-0.5 (6.38)
End of Treatment (n=23, 18)	0.4 (4.73)	-1.9 (5.47)

8.Secondary Outcome


Title	Change From Baseline in Pulmonary Artery Systolic Pressure (PASP)
Description	Pulmonary artery pressure was measured using transthoracic echocardiog...
Description	Pulmonary artery pressure was measured using transthoracic echocardiogram.
Time Frame	Baseline and Weeks 12, 24 and 36 and at end of treatment (median duration of treatment was 27 weeks in the bortezomib group and 40 weeks in the carfilzomib treatment group).

Outcome Measure Data

Analysis Population Description

Cardiopulmonary Safety Evaluable subgroup with available PASP data at baseline; "n" indicates participants whose results were available at both the baseline and the specified post-baseline visit.


Arm/Group Title	Bortezomib + DEX	Carfilzomib + DEX
Arm/Group Description:	Participants received bortezomib 1....	Participants received 20 mg/m² carf...
Arm/Group Description:	Participants received bortezomib 1.3 mg/m² administered intravenously (IV) or subcutaneously (SC) on Days 1, 4, 8, and 11 of a 21-day cycle plus dexamethasone (DEX) 20 mg administered on Days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle.	Participants received 20 mg/m² carfilzomib administered by IV infusion on Days 1 and 2 of Cycle 1, followed by 56 mg/m² on Days 8, 9, 15, and 16 of Cycle 1 and for each 28-day cycle thereafter. Additionally, participants received 20 mg dexamethasone on Days 1, 2, 8, 9, 15, 16, 22, and 23 of each 28 day cycle.
Overall Number of Participants Analyzed	52	45
Mean (Standard Deviation) Unit of Measure: mmHg
Week 12 (n=34, 30)	0.3 (11.72)	2.8 (11.44)
Week 24 (n=22, 20)	1.7 (8.47)	3.4 (13.63)
Week 36 (n=12, 14)	4.0 (7.24)	2.6 (13.55)
End of Treatment (n=21, 14)	3.4 (8.14)	0.9 (11.40)

Adverse Events

Time Frame	From the first dose of study drug up to 30 days after the last dose of study drug as of the data cut-off date of 03 January 2017; median duration of treatment was 27 weeks in the bortezomib group and 48 weeks in the carfilzomib treatment group.
Adverse Event Reporting Description	Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.

Arm/Group Title	Bortezomib	Carfilzomib
Arm/Group Description	[Not Specified]	[Not Specified]
Arm/Group Description	[Not Specified]	[Not Specified]
All-Cause Mortality
	Bortezomib	Carfilzomib
	Affected / at Risk (%)	Affected / at Risk (%)
Total	--/--	--/--
Serious Adverse Events Serious Adverse Events
	Bortezomib	Carfilzomib
	Affected / at Risk (%)	Affected / at Risk (%)
Total	182/456 (39.91%)	272/463 (58.75%)
Blood and lymphatic system disorders
ANAEMIA ^† 1	1/456 (0.22%)	4/463 (0.86%)
FEBRILE NEUTROPENIA ^† 1	3/456 (0.66%)	3/463 (0.65%)
HAEMORRHAGIC ANAEMIA ^† 1	0/456 (0.00%)	1/463 (0.22%)
NEUTROPENIA ^† 1	0/456 (0.00%)	1/463 (0.22%)
PLASMACYTOSIS ^† 1	0/456 (0.00%)	1/463 (0.22%)
THROMBOCYTOPENIA ^† 1	6/456 (1.32%)	4/463 (0.86%)
THROMBOTIC MICROANGIOPATHY ^† 1	0/456 (0.00%)	2/463 (0.43%)
THROMBOTIC THROMBOCYTOPENIC PURPURA ^† 1	0/456 (0.00%)	1/463 (0.22%)
Cardiac disorders
ACUTE CORONARY SYNDROME ^† 1	0/456 (0.00%)	2/463 (0.43%)
ACUTE LEFT VENTRICULAR FAILURE ^† 1	0/456 (0.00%)	1/463 (0.22%)
ACUTE MYOCARDIAL INFARCTION ^† 1	2/456 (0.44%)	1/463 (0.22%)
ANGINA PECTORIS ^† 1	0/456 (0.00%)	3/463 (0.65%)
AORTIC VALVE INCOMPETENCE ^† 1	1/456 (0.22%)	0/463 (0.00%)
ATRIAL FIBRILLATION ^† 1	4/456 (0.88%)	6/463 (1.30%)
ATRIAL FLUTTER ^† 1	1/456 (0.22%)	0/463 (0.00%)
BIFASCICULAR BLOCK ^† 1	1/456 (0.22%)	0/463 (0.00%)
CARDIAC ARREST ^† 1	1/456 (0.22%)	2/463 (0.43%)
CARDIAC FAILURE ^† 1	3/456 (0.66%)	9/463 (1.94%)
CARDIAC FAILURE ACUTE ^† 1	1/456 (0.22%)	2/463 (0.43%)
CARDIAC FAILURE CONGESTIVE ^† 1	0/456 (0.00%)	1/463 (0.22%)
CARDIAC HYPERTROPHY ^† 1	0/456 (0.00%)	1/463 (0.22%)
CARDIOMYOPATHY ^† 1	0/456 (0.00%)	2/463 (0.43%)
LEFT VENTRICULAR DYSFUNCTION ^† 1	0/456 (0.00%)	1/463 (0.22%)
LEFT VENTRICULAR FAILURE ^† 1	1/456 (0.22%)	0/463 (0.00%)
MYOCARDIAL INFARCTION ^† 1	2/456 (0.44%)	5/463 (1.08%)
PERICARDIAL EFFUSION ^† 1	0/456 (0.00%)	1/463 (0.22%)
PLEUROPERICARDITIS ^† 1	1/456 (0.22%)	0/463 (0.00%)
RIGHT VENTRICULAR FAILURE ^† 1	1/456 (0.22%)	1/463 (0.22%)
SINUS TACHYCARDIA ^† 1	0/456 (0.00%)	1/463 (0.22%)
STRESS CARDIOMYOPATHY ^† 1	1/456 (0.22%)	0/463 (0.00%)
SUPRAVENTRICULAR TACHYCARDIA ^† 1	0/456 (0.00%)	2/463 (0.43%)
Ear and labyrinth disorders
HEARING IMPAIRED ^† 1	1/456 (0.22%)	0/463 (0.00%)
Endocrine disorders
INAPPROPRIATE ANTIDIURETIC HORMONE SECRETION ^† 1	1/456 (0.22%)	0/463 (0.00%)
Eye disorders
CATARACT ^† 1	1/456 (0.22%)	0/463 (0.00%)
RETINAL TEAR ^† 1	1/456 (0.22%)	0/463 (0.00%)
Gastrointestinal disorders
ABDOMINAL DISTENSION ^† 1	1/456 (0.22%)	0/463 (0.00%)
ABDOMINAL PAIN ^† 1	2/456 (0.44%)	2/463 (0.43%)
ABDOMINAL PAIN UPPER ^† 1	1/456 (0.22%)	0/463 (0.00%)
ABDOMINAL STRANGULATED HERNIA ^† 1	0/456 (0.00%)	1/463 (0.22%)
COLITIS ^† 1	1/456 (0.22%)	0/463 (0.00%)
CONSTIPATION ^† 1	2/456 (0.44%)	1/463 (0.22%)
DIARRHOEA ^† 1	11/456 (2.41%)	5/463 (1.08%)
DIVERTICULUM ^† 1	0/456 (0.00%)	1/463 (0.22%)
ENTEROCOLITIS ^† 1	0/456 (0.00%)	1/463 (0.22%)
GASTRIC HAEMORRHAGE ^† 1	1/456 (0.22%)	0/463 (0.00%)
GASTROINTESTINAL DISORDER ^† 1	0/456 (0.00%)	1/463 (0.22%)
GASTROINTESTINAL HAEMORRHAGE ^† 1	2/456 (0.44%)	1/463 (0.22%)
ILEUS ^† 1	1/456 (0.22%)	0/463 (0.00%)
ILEUS PARALYTIC ^† 1	3/456 (0.66%)	0/463 (0.00%)
INTESTINAL OBSTRUCTION ^† 1	1/456 (0.22%)	0/463 (0.00%)
INTESTINAL POLYP HAEMORRHAGE ^† 1	1/456 (0.22%)	0/463 (0.00%)
LARGE INTESTINE PERFORATION ^† 1	0/456 (0.00%)	1/463 (0.22%)
LOWER GASTROINTESTINAL HAEMORRHAGE ^† 1	0/456 (0.00%)	1/463 (0.22%)
MELAENA ^† 1	1/456 (0.22%)	0/463 (0.00%)
NAUSEA ^† 1	3/456 (0.66%)	2/463 (0.43%)
PANCREATITIS ^† 1	0/456 (0.00%)	1/463 (0.22%)
PARAESTHESIA ORAL ^† 1	0/456 (0.00%)	1/463 (0.22%)
SMALL INTESTINAL OBSTRUCTION ^† 1	0/456 (0.00%)	1/463 (0.22%)
SUBILEUS ^† 1	1/456 (0.22%)	1/463 (0.22%)
VOMITING ^† 1	2/456 (0.44%)	5/463 (1.08%)
General disorders
ASTHENIA ^† 1	1/456 (0.22%)	0/463 (0.00%)
CARDIAC DEATH ^† 1	0/456 (0.00%)	1/463 (0.22%)
CHEST PAIN ^† 1	4/456 (0.88%)	3/463 (0.65%)
DEATH ^† 1	0/456 (0.00%)	1/463 (0.22%)
DEVICE OCCLUSION ^† 1	1/456 (0.22%)	0/463 (0.00%)
DISEASE PROGRESSION ^† 1	6/456 (1.32%)	8/463 (1.73%)
FATIGUE ^† 1	1/456 (0.22%)	3/463 (0.65%)
GENERAL PHYSICAL HEALTH DETERIORATION ^† 1	0/456 (0.00%)	4/463 (0.86%)
GENERALISED OEDEMA ^† 1	1/456 (0.22%)	0/463 (0.00%)
HYPERPYREXIA ^† 1	1/456 (0.22%)	0/463 (0.00%)
HYPERTHERMIA ^† 1	0/456 (0.00%)	1/463 (0.22%)
MALAISE ^† 1	1/456 (0.22%)	0/463 (0.00%)
NON-CARDIAC CHEST PAIN ^† 1	0/456 (0.00%)	1/463 (0.22%)
OEDEMA PERIPHERAL ^† 1	0/456 (0.00%)	1/463 (0.22%)
PAIN ^† 1	1/456 (0.22%)	0/463 (0.00%)
PYREXIA ^† 1	3/456 (0.66%)	19/463 (4.10%)
SUDDEN DEATH ^† 1	1/456 (0.22%)	3/463 (0.65%)
THROMBOSIS IN DEVICE ^† 1	1/456 (0.22%)	0/463 (0.00%)
Hepatobiliary disorders
BILE DUCT STONE ^† 1	0/456 (0.00%)	1/463 (0.22%)
CHOLECYSTITIS ACUTE ^† 1	1/456 (0.22%)	0/463 (0.00%)
CHOLELITHIASIS ^† 1	2/456 (0.44%)	0/463 (0.00%)
HEPATIC FAILURE ^† 1	0/456 (0.00%)	2/463 (0.43%)
HEPATOCELLULAR INJURY ^† 1	0/456 (0.00%)	1/463 (0.22%)
JAUNDICE CHOLESTATIC ^† 1	0/456 (0.00%)	1/463 (0.22%)
LIVER DISORDER ^† 1	0/456 (0.00%)	1/463 (0.22%)
Immune system disorders
HYPERSENSITIVITY ^† 1	1/456 (0.22%)	0/463 (0.00%)
HYPOGAMMAGLOBULINAEMIA ^† 1	0/456 (0.00%)	1/463 (0.22%)
Infections and infestations
ABDOMINAL INFECTION ^† 1	0/456 (0.00%)	1/463 (0.22%)
ABSCESS LIMB ^† 1	0/456 (0.00%)	1/463 (0.22%)
ACUTE SINUSITIS ^† 1	0/456 (0.00%)	1/463 (0.22%)
APPENDICITIS ^† 1	0/456 (0.00%)	1/463 (0.22%)
BACTERAEMIA ^† 1	0/456 (0.00%)	1/463 (0.22%)
BACTERIAL DIARRHOEA ^† 1	0/456 (0.00%)	1/463 (0.22%)
BACTERIAL INFECTION ^† 1	2/456 (0.44%)	1/463 (0.22%)
BREAST ABSCESS ^† 1	1/456 (0.22%)	0/463 (0.00%)
BRONCHIOLITIS ^† 1	0/456 (0.00%)	2/463 (0.43%)
BRONCHITIS ^† 1	2/456 (0.44%)	8/463 (1.73%)
BRONCHOPNEUMONIA ^† 1	1/456 (0.22%)	7/463 (1.51%)
BRONCHOPULMONARY ASPERGILLOSIS ^† 1	0/456 (0.00%)	1/463 (0.22%)
BURSITIS INFECTIVE ^† 1	1/456 (0.22%)	1/463 (0.22%)
CATHETER SITE INFECTION ^† 1	0/456 (0.00%)	1/463 (0.22%)
CELLULITIS ^† 1	1/456 (0.22%)	3/463 (0.65%)
CLOSTRIDIAL INFECTION ^† 1	0/456 (0.00%)	1/463 (0.22%)
CLOSTRIDIUM DIFFICILE SEPSIS ^† 1	1/456 (0.22%)	0/463 (0.00%)
CORONA VIRUS INFECTION ^† 1	1/456 (0.22%)	0/463 (0.00%)
DEVICE RELATED INFECTION ^† 1	0/456 (0.00%)	2/463 (0.43%)
DIVERTICULITIS ^† 1	0/456 (0.00%)	3/463 (0.65%)
ENCEPHALITIC INFECTION ^† 1	0/456 (0.00%)	1/463 (0.22%)
ENCEPHALITIS HERPES ^† 1	0/456 (0.00%)	1/463 (0.22%)
ENTERITIS INFECTIOUS ^† 1	0/456 (0.00%)	1/463 (0.22%)
ERYSIPELAS ^† 1	0/456 (0.00%)	1/463 (0.22%)
ESCHERICHIA BACTERAEMIA ^† 1	0/456 (0.00%)	1/463 (0.22%)
ESCHERICHIA URINARY TRACT INFECTION ^† 1	0/456 (0.00%)	1/463 (0.22%)
FEBRILE INFECTION ^† 1	0/456 (0.00%)	2/463 (0.43%)
GASTROENTERITIS ^† 1	4/456 (0.88%)	5/463 (1.08%)
GASTROENTERITIS VIRAL ^† 1	1/456 (0.22%)	1/463 (0.22%)
H1N1 INFLUENZA ^† 1	0/456 (0.00%)	1/463 (0.22%)
HAEMOPHILUS SEPSIS ^† 1	0/456 (0.00%)	1/463 (0.22%)
HERPES ZOSTER ^† 1	1/456 (0.22%)	0/463 (0.00%)
INFECTION ^† 1	0/456 (0.00%)	4/463 (0.86%)
INFECTIOUS PLEURAL EFFUSION ^† 1	0/456 (0.00%)	1/463 (0.22%)
INFECTIVE EXACERBATION OF CHRONIC OBSTRUCTIVE AIRWAYS DISEASE ^† 1	1/456 (0.22%)	1/463 (0.22%)
INFLUENZA ^† 1	1/456 (0.22%)	3/463 (0.65%)
LISTERIOSIS ^† 1	0/456 (0.00%)	1/463 (0.22%)
LOBAR PNEUMONIA ^† 1	1/456 (0.22%)	2/463 (0.43%)
LOWER RESPIRATORY TRACT INFECTION ^† 1	5/456 (1.10%)	7/463 (1.51%)
LOWER RESPIRATORY TRACT INFECTION VIRAL ^† 1	0/456 (0.00%)	1/463 (0.22%)
LUNG INFECTION ^† 1	3/456 (0.66%)	5/463 (1.08%)
NECROTISING ULCERATIVE PERIODONTITIS ^† 1	0/456 (0.00%)	1/463 (0.22%)
ORAL FUNGAL INFECTION ^† 1	0/456 (0.00%)	1/463 (0.22%)
OSTEOMYELITIS ^† 1	0/456 (0.00%)	1/463 (0.22%)
PARAINFLUENZAE VIRUS INFECTION ^† 1	0/456 (0.00%)	2/463 (0.43%)
PHARYNGITIS ^† 1	1/456 (0.22%)	0/463 (0.00%)
PNEUMOCOCCAL INFECTION ^† 1	0/456 (0.00%)	1/463 (0.22%)
PNEUMOCYSTIS JIROVECI PNEUMONIA ^† 1	1/456 (0.22%)	0/463 (0.00%)
PNEUMONIA ^† 1	42/456 (9.21%)	39/463 (8.42%)
PNEUMONIA BACTERIAL ^† 1	1/456 (0.22%)	1/463 (0.22%)
PNEUMONIA INFLUENZAL ^† 1	0/456 (0.00%)	1/463 (0.22%)
PNEUMONIA MORAXELLA ^† 1	1/456 (0.22%)	0/463 (0.00%)
PNEUMONIA PNEUMOCOCCAL ^† 1	1/456 (0.22%)	1/463 (0.22%)
PSEUDOMEMBRANOUS COLITIS ^† 1	1/456 (0.22%)	0/463 (0.00%)
PULMONARY SEPSIS ^† 1	1/456 (0.22%)	0/463 (0.00%)
PYELONEPHRITIS ACUTE ^† 1	0/456 (0.00%)	1/463 (0.22%)
RESPIRATORY SYNCYTIAL VIRUS INFECTION ^† 1	2/456 (0.44%)	0/463 (0.00%)
RESPIRATORY TRACT INFECTION ^† 1	5/456 (1.10%)	10/463 (2.16%)
RESPIRATORY TRACT INFECTION VIRAL ^† 1	1/456 (0.22%)	2/463 (0.43%)
SEPSIS ^† 1	4/456 (0.88%)	7/463 (1.51%)
SEPTIC SHOCK ^† 1	3/456 (0.66%)	4/463 (0.86%)
SINUSITIS ^† 1	0/456 (0.00%)	1/463 (0.22%)
STREPTOCOCCAL BACTERAEMIA ^† 1	0/456 (0.00%)	1/463 (0.22%)
TRACHEOBRONCHITIS ^† 1	0/456 (0.00%)	1/463 (0.22%)
UPPER RESPIRATORY TRACT INFECTION ^† 1	3/456 (0.66%)	7/463 (1.51%)
URINARY TRACT INFECTION ^† 1	4/456 (0.88%)	6/463 (1.30%)
UROSEPSIS ^† 1	3/456 (0.66%)	0/463 (0.00%)
VIRAL INFECTION ^† 1	0/456 (0.00%)	1/463 (0.22%)
VIRAL UPPER RESPIRATORY TRACT INFECTION ^† 1	0/456 (0.00%)	1/463 (0.22%)
Injury, poisoning and procedural complications
CHEST INJURY ^† 1	0/456 (0.00%)	1/463 (0.22%)
COMPRESSION FRACTURE ^† 1	0/456 (0.00%)	1/463 (0.22%)
FACIAL BONES FRACTURE ^† 1	1/456 (0.22%)	1/463 (0.22%)
FEMORAL NECK FRACTURE ^† 1	1/456 (0.22%)	0/463 (0.00%)
FEMUR FRACTURE ^† 1	1/456 (0.22%)	0/463 (0.00%)
FOOT FRACTURE ^† 1	0/456 (0.00%)	1/463 (0.22%)
FRACTURE ^† 1	1/456 (0.22%)	0/463 (0.00%)
HEAD INJURY ^† 1	1/456 (0.22%)	1/463 (0.22%)
HIP FRACTURE ^† 1	0/456 (0.00%)	1/463 (0.22%)
HUMERUS FRACTURE ^† 1	0/456 (0.00%)	3/463 (0.65%)
INFUSION RELATED REACTION ^† 1	0/456 (0.00%)	3/463 (0.65%)
LIGAMENT SPRAIN ^† 1	1/456 (0.22%)	0/463 (0.00%)
OPEN WOUND ^† 1	1/456 (0.22%)	0/463 (0.00%)
PUBIS FRACTURE ^† 1	1/456 (0.22%)	0/463 (0.00%)
SPINAL COMPRESSION FRACTURE ^† 1	1/456 (0.22%)	1/463 (0.22%)
ULNA FRACTURE ^† 1	1/456 (0.22%)	0/463 (0.00%)
UPPER LIMB FRACTURE ^† 1	0/456 (0.00%)	1/463 (0.22%)
Investigations
ALANINE AMINOTRANSFERASE INCREASED ^† 1	0/456 (0.00%)	1/463 (0.22%)
ASPARTATE AMINOTRANSFERASE INCREASED ^† 1	0/456 (0.00%)	1/463 (0.22%)
BLOOD CORTISOL DECREASED ^† 1	0/456 (0.00%)	1/463 (0.22%)
BLOOD CREATININE INCREASED ^† 1	0/456 (0.00%)	2/463 (0.43%)
INFLUENZA B VIRUS TEST POSITIVE ^† 1	0/456 (0.00%)	1/463 (0.22%)
LYMPHOCYTE COUNT DECREASED ^† 1	1/456 (0.22%)	0/463 (0.00%)
PLATELET COUNT DECREASED ^† 1	3/456 (0.66%)	2/463 (0.43%)
TROPONIN T INCREASED ^† 1	1/456 (0.22%)	1/463 (0.22%)
Metabolism and nutrition disorders
DECREASED APPETITE ^† 1	2/456 (0.44%)	0/463 (0.00%)
DEHYDRATION ^† 1	3/456 (0.66%)	0/463 (0.00%)
DIABETES MELLITUS ^† 1	1/456 (0.22%)	2/463 (0.43%)
DIABETES MELLITUS INADEQUATE CONTROL ^† 1	1/456 (0.22%)	0/463 (0.00%)
HYPERCALCAEMIA ^† 1	5/456 (1.10%)	0/463 (0.00%)
HYPERGLYCAEMIA ^† 1	1/456 (0.22%)	4/463 (0.86%)
HYPERKALAEMIA ^† 1	1/456 (0.22%)	1/463 (0.22%)
HYPOGLYCAEMIA ^† 1	0/456 (0.00%)	3/463 (0.65%)
HYPONATRAEMIA ^† 1	1/456 (0.22%)	2/463 (0.43%)
HYPOVOLAEMIA ^† 1	0/456 (0.00%)	1/463 (0.22%)
TUMOUR LYSIS SYNDROME ^† 1	0/456 (0.00%)	1/463 (0.22%)
Musculoskeletal and connective tissue disorders
ARTHRALGIA ^† 1	3/456 (0.66%)	1/463 (0.22%)
BACK PAIN ^† 1	3/456 (0.66%)	6/463 (1.30%)
BONE PAIN ^† 1	0/456 (0.00%)	4/463 (0.86%)
FLANK PAIN ^† 1	0/456 (0.00%)	1/463 (0.22%)
INTERVERTEBRAL DISC PROTRUSION ^† 1	0/456 (0.00%)	1/463 (0.22%)
LUMBAR SPINAL STENOSIS ^† 1	1/456 (0.22%)	2/463 (0.43%)
MOBILITY DECREASED ^† 1	0/456 (0.00%)	1/463 (0.22%)
MUSCULAR WEAKNESS ^† 1	1/456 (0.22%)	1/463 (0.22%)
MUSCULOSKELETAL CHEST PAIN ^† 1	0/456 (0.00%)	1/463 (0.22%)
MUSCULOSKELETAL PAIN ^† 1	1/456 (0.22%)	1/463 (0.22%)
MYALGIA ^† 1	0/456 (0.00%)	1/463 (0.22%)
OSTEOARTHRITIS ^† 1	0/456 (0.00%)	1/463 (0.22%)
OSTEONECROSIS OF JAW ^† 1	0/456 (0.00%)	1/463 (0.22%)
PAIN IN EXTREMITY ^† 1	1/456 (0.22%)	0/463 (0.00%)
PATHOLOGICAL FRACTURE ^† 1	1/456 (0.22%)	0/463 (0.00%)
RHABDOMYOLYSIS ^† 1	0/456 (0.00%)	1/463 (0.22%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
ACUTE MYELOID LEUKAEMIA ^† 1	0/456 (0.00%)	1/463 (0.22%)
BASAL CELL CARCINOMA ^† 1	0/456 (0.00%)	2/463 (0.43%)
BLADDER TRANSITIONAL CELL CARCINOMA ^† 1	0/456 (0.00%)	1/463 (0.22%)
CANCER PAIN ^† 1	0/456 (0.00%)	1/463 (0.22%)
CARCINOMA IN SITU ^† 1	0/456 (0.00%)	1/463 (0.22%)
COLON CANCER ^† 1	1/456 (0.22%)	1/463 (0.22%)
MENINGEAL NEOPLASM ^† 1	0/456 (0.00%)	1/463 (0.22%)
METASTASES TO SPINE ^† 1	0/456 (0.00%)	1/463 (0.22%)
MULTIPLE MYELOMA ^† 1	1/456 (0.22%)	5/463 (1.08%)
OESOPHAGEAL SQUAMOUS CELL CARCINOMA ^† 1	1/456 (0.22%)	0/463 (0.00%)
PLASMACYTOMA ^† 1	0/456 (0.00%)	5/463 (1.08%)
PLEURAL MESOTHELIOMA ^† 1	1/456 (0.22%)	0/463 (0.00%)
RECTAL CANCER ^† 1	0/456 (0.00%)	1/463 (0.22%)
SQUAMOUS CELL CARCINOMA ^† 1	1/456 (0.22%)	0/463 (0.00%)
TONGUE NEOPLASM MALIGNANT STAGE UNSPECIFIED ^† 1	0/456 (0.00%)	1/463 (0.22%)
Nervous system disorders
ACQUIRED EPILEPTIC APHASIA ^† 1	0/456 (0.00%)	1/463 (0.22%)
CENTRAL NERVOUS SYSTEM LESION ^† 1	1/456 (0.22%)	0/463 (0.00%)
CEREBROVASCULAR ACCIDENT ^† 1	0/456 (0.00%)	4/463 (0.86%)
COGNITIVE DISORDER ^† 1	1/456 (0.22%)	0/463 (0.00%)
CONVULSION ^† 1	1/456 (0.22%)	0/463 (0.00%)
DEPRESSED LEVEL OF CONSCIOUSNESS ^† 1	1/456 (0.22%)	0/463 (0.00%)
DIZZINESS ^† 1	1/456 (0.22%)	0/463 (0.00%)
ENCEPHALOPATHY ^† 1	0/456 (0.00%)	1/463 (0.22%)
HEADACHE ^† 1	0/456 (0.00%)	2/463 (0.43%)
HYPERCAPNIC COMA ^† 1	0/456 (0.00%)	1/463 (0.22%)
HYPERTENSIVE ENCEPHALOPATHY ^† 1	1/456 (0.22%)	0/463 (0.00%)
ISCHAEMIC STROKE ^† 1	0/456 (0.00%)	3/463 (0.65%)
LETHARGY ^† 1	0/456 (0.00%)	1/463 (0.22%)
LOSS OF CONSCIOUSNESS ^† 1	1/456 (0.22%)	0/463 (0.00%)
METABOLIC ENCEPHALOPATHY ^† 1	1/456 (0.22%)	0/463 (0.00%)
NEURALGIA ^† 1	1/456 (0.22%)	1/463 (0.22%)
NEUROPATHY PERIPHERAL ^† 1	2/456 (0.44%)	1/463 (0.22%)
PARAPARESIS ^† 1	1/456 (0.22%)	0/463 (0.00%)
PARAPLEGIA ^† 1	0/456 (0.00%)	1/463 (0.22%)
POLYNEUROPATHY ^† 1	1/456 (0.22%)	0/463 (0.00%)
POSTERIOR REVERSIBLE ENCEPHALOPATHY SYNDROME ^† 1	0/456 (0.00%)	2/463 (0.43%)
RADICULITIS BRACHIAL ^† 1	0/456 (0.00%)	1/463 (0.22%)
RADICULOPATHY ^† 1	0/456 (0.00%)	1/463 (0.22%)
SCIATICA ^† 1	1/456 (0.22%)	0/463 (0.00%)
SPINAL CORD COMPRESSION ^† 1	2/456 (0.44%)	4/463 (0.86%)
SYNCOPE ^† 1	4/456 (0.88%)	1/463 (0.22%)
TRANSIENT ISCHAEMIC ATTACK ^† 1	2/456 (0.44%)	0/463 (0.00%)
Psychiatric disorders
COMPLETED SUICIDE ^† 1	0/456 (0.00%)	1/463 (0.22%)
CONFUSIONAL STATE ^† 1	4/456 (0.88%)	4/463 (0.86%)
DEPRESSION ^† 1	1/456 (0.22%)	1/463 (0.22%)
DYSTHYMIC DISORDER ^† 1	1/456 (0.22%)	0/463 (0.00%)
MENTAL DISORDER ^† 1	0/456 (0.00%)	1/463 (0.22%)
PSYCHOTIC DISORDER ^† 1	0/456 (0.00%)	1/463 (0.22%)
Renal and urinary disorders
ALBUMINURIA ^† 1	0/456 (0.00%)	1/463 (0.22%)
ANURIA ^† 1	0/456 (0.00%)	1/463 (0.22%)
NEPHROPATHY ^† 1	1/456 (0.22%)	1/463 (0.22%)
NEPHROTIC SYNDROME ^† 1	0/456 (0.00%)	1/463 (0.22%)
PROTEINURIA ^† 1	0/456 (0.00%)	1/463 (0.22%)
RENAL FAILURE ^† 1	0/456 (0.00%)	5/463 (1.08%)
RENAL FAILURE ACUTE ^† 1	7/456 (1.54%)	11/463 (2.38%)
RENAL IMPAIRMENT ^† 1	2/456 (0.44%)	1/463 (0.22%)
URINARY RETENTION ^† 1	1/456 (0.22%)	0/463 (0.00%)
Reproductive system and breast disorders
PROSTATOMEGALY ^† 1	1/456 (0.22%)	0/463 (0.00%)
UTERINE HAEMORRHAGE ^† 1	0/456 (0.00%)	1/463 (0.22%)
Respiratory, thoracic and mediastinal disorders
ACUTE PULMONARY OEDEMA ^† 1	1/456 (0.22%)	3/463 (0.65%)
ACUTE RESPIRATORY DISTRESS SYNDROME ^† 1	1/456 (0.22%)	1/463 (0.22%)
ACUTE RESPIRATORY FAILURE ^† 1	1/456 (0.22%)	0/463 (0.00%)
ASTHMA ^† 1	1/456 (0.22%)	3/463 (0.65%)
BRONCHOPNEUMOPATHY ^† 1	1/456 (0.22%)	0/463 (0.00%)
CHRONIC OBSTRUCTIVE PULMONARY DISEASE ^† 1	1/456 (0.22%)	2/463 (0.43%)
DYSPNOEA ^† 1	1/456 (0.22%)	18/463 (3.89%)
EPISTAXIS ^† 1	1/456 (0.22%)	1/463 (0.22%)
HYPOXIA ^† 1	1/456 (0.22%)	0/463 (0.00%)
INTERSTITIAL LUNG DISEASE ^† 1	0/456 (0.00%)	2/463 (0.43%)
LUNG DISORDER ^† 1	1/456 (0.22%)	3/463 (0.65%)
PLEURAL EFFUSION ^† 1	1/456 (0.22%)	2/463 (0.43%)
PNEUMONITIS ^† 1	1/456 (0.22%)	2/463 (0.43%)
PULMONARY ARTERIAL HYPERTENSION ^† 1	0/456 (0.00%)	1/463 (0.22%)
PULMONARY EMBOLISM ^† 1	3/456 (0.66%)	10/463 (2.16%)
PULMONARY HYPERTENSION ^† 1	0/456 (0.00%)	3/463 (0.65%)
PULMONARY OEDEMA ^† 1	1/456 (0.22%)	2/463 (0.43%)
RESPIRATORY FAILURE ^† 1	0/456 (0.00%)	4/463 (0.86%)
Skin and subcutaneous tissue disorders
DRUG ERUPTION ^† 1	0/456 (0.00%)	1/463 (0.22%)
ECZEMA ^† 1	0/456 (0.00%)	1/463 (0.22%)
ERYTHEMA MULTIFORME ^† 1	1/456 (0.22%)	0/463 (0.00%)
PRURITUS GENERALISED ^† 1	1/456 (0.22%)	0/463 (0.00%)
PURPURA ^† 1	0/456 (0.00%)	1/463 (0.22%)
Surgical and medical procedures
COLOSTOMY CLOSURE ^† 1	0/456 (0.00%)	1/463 (0.22%)
HAEMORRHOID OPERATION ^† 1	0/456 (0.00%)	1/463 (0.22%)
REMOVAL OF INTERNAL FIXATION ^† 1	1/456 (0.22%)	0/463 (0.00%)
Vascular disorders
AORTIC ANEURYSM ^† 1	0/456 (0.00%)	1/463 (0.22%)
AORTIC EMBOLUS ^† 1	0/456 (0.00%)	1/463 (0.22%)
CIRCULATORY COLLAPSE ^† 1	1/456 (0.22%)	1/463 (0.22%)
DEEP VEIN THROMBOSIS ^† 1	3/456 (0.66%)	5/463 (1.08%)
HAEMATOMA ^† 1	0/456 (0.00%)	1/463 (0.22%)
HYPERTENSION ^† 1	0/456 (0.00%)	3/463 (0.65%)
HYPERTENSIVE CRISIS ^† 1	0/456 (0.00%)	1/463 (0.22%)
HYPOTENSION ^† 1	4/456 (0.88%)	1/463 (0.22%)
MALIGNANT HYPERTENSION ^† 1	0/456 (0.00%)	1/463 (0.22%)
ORTHOSTATIC HYPOTENSION ^† 1	4/456 (0.88%)	0/463 (0.00%)
PERIPHERAL ARTERIAL OCCLUSIVE DISEASE ^† 1	0/456 (0.00%)	2/463 (0.43%)
THROMBOPHLEBITIS ^† 1	0/456 (0.00%)	1/463 (0.22%)
VENA CAVA THROMBOSIS ^† 1	0/456 (0.00%)	1/463 (0.22%)
VENOUS THROMBOSIS LIMB ^† 1	0/456 (0.00%)	1/463 (0.22%)
† Indicates events were collected by systematic assessment 1 Term from vocabulary, MedDRA 15.1
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Bortezomib	Carfilzomib
	Affected / at Risk (%)	Affected / at Risk (%)
Total	435/456 (95.39%)	446/463 (96.33%)
Blood and lymphatic system disorders
ANAEMIA ^† 1	129/456 (28.29%)	196/463 (42.33%)
LYMPHOPENIA ^† 1	25/456 (5.48%)	31/463 (6.70%)
NEUTROPENIA ^† 1	26/456 (5.70%)	27/463 (5.83%)
THROMBOCYTOPENIA ^† 1	83/456 (18.20%)	100/463 (21.60%)
Eye disorders
CATARACT ^† 1	17/456 (3.73%)	32/463 (6.91%)
CONJUNCTIVITIS ^† 1	36/456 (7.89%)	22/463 (4.75%)
Gastrointestinal disorders
ABDOMINAL DISTENSION ^† 1	26/456 (5.70%)	20/463 (4.32%)
ABDOMINAL PAIN ^† 1	38/456 (8.33%)	32/463 (6.91%)
ABDOMINAL PAIN UPPER ^† 1	35/456 (7.68%)	24/463 (5.18%)
CONSTIPATION ^† 1	126/456 (27.63%)	75/463 (16.20%)
DIARRHOEA ^† 1	184/456 (40.35%)	167/463 (36.07%)
DYSPEPSIA ^† 1	25/456 (5.48%)	35/463 (7.56%)
NAUSEA ^† 1	89/456 (19.52%)	108/463 (23.33%)
VOMITING ^† 1	44/456 (9.65%)	75/463 (16.20%)
General disorders
ASTHENIA ^† 1	78/456 (17.11%)	107/463 (23.11%)
CHEST PAIN ^† 1	19/456 (4.17%)	42/463 (9.07%)
CHILLS ^† 1	12/456 (2.63%)	26/463 (5.62%)
FATIGUE ^† 1	140/456 (30.70%)	149/463 (32.18%)
INFLUENZA LIKE ILLNESS ^† 1	10/456 (2.19%)	24/463 (5.18%)
MALAISE ^† 1	8/456 (1.75%)	24/463 (5.18%)
OEDEMA PERIPHERAL ^† 1	87/456 (19.08%)	116/463 (25.05%)
PYREXIA ^† 1	68/456 (14.91%)	144/463 (31.10%)
Infections and infestations
BRONCHITIS ^† 1	46/456 (10.09%)	103/463 (22.25%)
NASOPHARYNGITIS ^† 1	61/456 (13.38%)	81/463 (17.49%)
PNEUMONIA ^† 1	18/456 (3.95%)	24/463 (5.18%)
RESPIRATORY TRACT INFECTION ^† 1	29/456 (6.36%)	47/463 (10.15%)
RHINITIS ^† 1	10/456 (2.19%)	29/463 (6.26%)
UPPER RESPIRATORY TRACT INFECTION ^† 1	80/456 (17.54%)	116/463 (25.05%)
URINARY TRACT INFECTION ^† 1	28/456 (6.14%)	34/463 (7.34%)
Injury, poisoning and procedural complications
CONTUSION ^† 1	25/456 (5.48%)	19/463 (4.10%)
FALL ^† 1	23/456 (5.04%)	18/463 (3.89%)
Investigations
BLOOD CREATININE INCREASED ^† 1	28/456 (6.14%)	52/463 (11.23%)
CREATININE RENAL CLEARANCE DECREASED ^† 1	18/456 (3.95%)	29/463 (6.26%)
LYMPHOCYTE COUNT DECREASED ^† 1	18/456 (3.95%)	42/463 (9.07%)
PLATELET COUNT DECREASED ^† 1	41/456 (8.99%)	57/463 (12.31%)
Metabolism and nutrition disorders
DECREASED APPETITE ^† 1	61/456 (13.38%)	50/463 (10.80%)
HYPERGLYCAEMIA ^† 1	42/456 (9.21%)	53/463 (11.45%)
HYPERURICAEMIA ^† 1	8/456 (1.75%)	31/463 (6.70%)
HYPOCALCAEMIA ^† 1	19/456 (4.17%)	27/463 (5.83%)
HYPOKALAEMIA ^† 1	51/456 (11.18%)	60/463 (12.96%)
HYPOPHOSPHATAEMIA ^† 1	28/456 (6.14%)	32/463 (6.91%)
Musculoskeletal and connective tissue disorders
ARTHRALGIA ^† 1	51/456 (11.18%)	60/463 (12.96%)
BACK PAIN ^† 1	81/456 (17.76%)	105/463 (22.68%)
BONE PAIN ^† 1	40/456 (8.77%)	55/463 (11.88%)
MUSCLE SPASMS ^† 1	28/456 (6.14%)	92/463 (19.87%)
MUSCULAR WEAKNESS ^† 1	47/456 (10.31%)	44/463 (9.50%)
MUSCULOSKELETAL CHEST PAIN ^† 1	20/456 (4.39%)	39/463 (8.42%)
MUSCULOSKELETAL PAIN ^† 1	23/456 (5.04%)	24/463 (5.18%)
MYALGIA ^† 1	18/456 (3.95%)	28/463 (6.05%)
PAIN IN EXTREMITY ^† 1	50/456 (10.96%)	55/463 (11.88%)
Nervous system disorders
DIZZINESS ^† 1	69/456 (15.13%)	42/463 (9.07%)
DYSGEUSIA ^† 1	27/456 (5.92%)	16/463 (3.46%)
HEADACHE ^† 1	49/456 (10.75%)	95/463 (20.52%)
HYPOAESTHESIA ^† 1	14/456 (3.07%)	24/463 (5.18%)
NEURALGIA ^† 1	72/456 (15.79%)	11/463 (2.38%)
NEUROPATHY PERIPHERAL ^† 1	130/456 (28.51%)	49/463 (10.58%)
PARAESTHESIA ^† 1	76/456 (16.67%)	43/463 (9.29%)
PERIPHERAL SENSORY NEUROPATHY ^† 1	70/456 (15.35%)	29/463 (6.26%)
POLYNEUROPATHY ^† 1	26/456 (5.70%)	6/463 (1.30%)
TREMOR ^† 1	23/456 (5.04%)	10/463 (2.16%)
Psychiatric disorders
ANXIETY ^† 1	33/456 (7.24%)	19/463 (4.10%)
INSOMNIA ^† 1	122/456 (26.75%)	125/463 (27.00%)
Respiratory, thoracic and mediastinal disorders
COUGH ^† 1	72/456 (15.79%)	128/463 (27.65%)
DYSPNOEA ^† 1	62/456 (13.60%)	144/463 (31.10%)
EPISTAXIS ^† 1	14/456 (3.07%)	24/463 (5.18%)
OROPHARYNGEAL PAIN ^† 1	19/456 (4.17%)	28/463 (6.05%)
PRODUCTIVE COUGH ^† 1	15/456 (3.29%)	27/463 (5.83%)
Skin and subcutaneous tissue disorders
PRURITUS ^† 1	29/456 (6.36%)	34/463 (7.34%)
RASH ^† 1	35/456 (7.68%)	41/463 (8.86%)
Vascular disorders
FLUSHING ^† 1	7/456 (1.54%)	24/463 (5.18%)
HYPERTENSION ^† 1	45/456 (9.87%)	148/463 (31.97%)
HYPOTENSION ^† 1	37/456 (8.11%)	29/463 (6.26%)
† Indicates events were collected by systematic assessment 1 Term from vocabulary, MedDRA 15.1

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

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.

Results Point of Contact

Layout table for Results Point of Contact information

Name/Title:	Study Director
Organization:	Amgen Inc.
Phone:	866-572-6436

Publications:

Moreau P, Joshua D, Chng WJ, Palumbo A, Goldschmidt H, Hajek R, Facon T, Ludwig H, Pour L, Niesvizky R, Oriol A, Rosinol L, Suvorov A, Gaidano G, Pika T, Weisel K, Goranova-Marinova V, Gillenwater HH, Mohamed N, Aggarwal S, Feng S, Dimopoulos MA. Impact of prior treatment on patients with relapsed multiple myeloma treated with carfilzomib and dexamethasone vs bortezomib and dexamethasone in the phase 3 ENDEAVOR study. Leukemia. 2017 Jan;31(1):115-122. doi: 10.1038/leu.2016.186. Epub 2016 Jul 4.

Chng WJ, Goldschmidt H, Dimopoulos MA, Moreau P, Joshua D, Palumbo A, Facon T, Ludwig H, Pour L, Niesvizky R, Oriol A, Rosinol L, Suvorov A, Gaidano G, Pika T, Weisel K, Goranova-Marinova V, Gillenwater HH, Mohamed N, Feng S, Aggarwal S, Hajek R. Carfilzomib-dexamethasone vs bortezomib-dexamethasone in relapsed or refractory multiple myeloma by cytogenetic risk in the phase 3 study ENDEAVOR. Leukemia. 2017 Jun;31(6):1368-1374. doi: 10.1038/leu.2016.390. Epub 2016 Dec 27.

Dimopoulos MA, Goldschmidt H, Niesvizky R, Joshua D, Chng WJ, Oriol A, Orlowski RZ, Ludwig H, Facon T, Hajek R, Weisel K, Hungria V, Minuk L, Feng S, Zahlten-Kumeli A, Kimball AS, Moreau P. Carfilzomib or bortezomib in relapsed or refractory multiple myeloma (ENDEAVOR): an interim overall survival analysis of an open-label, randomised, phase 3 trial. Lancet Oncol. 2017 Oct;18(10):1327-1337. doi: 10.1016/S1470-2045(17)30578-8. Epub 2017 Aug 23. Erratum In: Lancet Oncol. 2017 Oct;18(10):e562.

Ludwig H, Dimopoulos MA, Moreau P, Chng WJ, Goldschmidt H, Hajek R, Facon T, Pour L, Niesvizky R, Oriol A, Rosinol L, Suvorov A, Gaidano G, Pika T, Weisel K, Goranova-Marinova V, Palumbo A, Gillenwater HH, Mohamed N, Aggarwal S, Feng S, Joshua D. Carfilzomib and dexamethasone vs bortezomib and dexamethasone in patients with relapsed multiple myeloma: results of the phase 3 study ENDEAVOR (NCT01568866) according to age subgroup. Leuk Lymphoma. 2017 Oct;58(10):2501-2504. doi: 10.1080/10428194.2017.1298755. Epub 2017 Mar 17. No abstract available.

Chari A, Stewart AK, Russell SD, Moreau P, Herrmann J, Banchs J, Hajek R, Groarke J, Lyon AR, Batty GN, Ro S, Huang M, Iskander KS, Lenihan D. Analysis of carfilzomib cardiovascular safety profile across relapsed and/or refractory multiple myeloma clinical trials. Blood Adv. 2018 Jul 10;2(13):1633-1644. doi: 10.1182/bloodadvances.2017015545.

Dimopoulos M, Siegel D, White DJ, Boccia R, Iskander KS, Yang Z, Kimball AS, Mezzi K, Ludwig H, Niesvizky R. Carfilzomib vs bortezomib in patients with multiple myeloma and renal failure: a subgroup analysis of ENDEAVOR. Blood. 2019 Jan 10;133(2):147-155. doi: 10.1182/blood-2018-06-860015. Epub 2018 Nov 26.

Facon T, Niesvizky R, Mateos MV, Siegel D, Rosenbaum C, Bringhen S, Weisel K, Ho PJ, Ludwig H, Kumar S, Wang K, Obreja M, Yang Z, Klippel Z, Mezzi K, Goldrick A, Tekle C, Dimopoulos MA. Efficacy and safety of carfilzomib-based regimens in frail patients with relapsed and/or refractory multiple myeloma. Blood Adv. 2020 Nov 10;4(21):5449-5459. doi: 10.1182/bloodadvances.2020001965.

Hari P, Mateos MV, Abonour R, Knop S, Bensinger W, Ludwig H, Song K, Hajek R, Moreau P, Siegel DS, Feng S, Obreja M, Aggarwal SK, Iskander K, Goldschmidt H. Efficacy and safety of carfilzomib regimens in multiple myeloma patients relapsing after autologous stem cell transplant: ASPIRE and ENDEAVOR outcomes. Leukemia. 2017 Dec;31(12):2630-2641. doi: 10.1038/leu.2017.122. Epub 2017 Apr 25.

Leleu X, Martin TG, Einsele H, Lyons RM, Durie BGM, Iskander KS, Ailawadhi S. Role of Proteasome Inhibitors in Relapsed and/or Refractory Multiple Myeloma. Clin Lymphoma Myeloma Leuk. 2019 Jan;19(1):9-22. doi: 10.1016/j.clml.2018.08.016. Epub 2018 Sep 5.

Ludwig H, Moreau P, Dimopoulos MA, Mateos MV, Kaiser M, Hajek R, Feng S, Cocks K, Buchanan J, Weisel K. Health-related quality of life in the ENDEAVOR study: carfilzomib-dexamethasone vs bortezomib-dexamethasone in relapsed/refractory multiple myeloma. Blood Cancer J. 2019 Feb 22;9(3):23. doi: 10.1038/s41408-019-0181-0.

Mateos MV, Goldschmidt H, San-Miguel J, Mikhael J, DeCosta L, Zhou L, Obreja M, Blaedel J, Szabo Z, Leleu X. Carfilzomib in relapsed or refractory multiple myeloma patients with early or late relapse following prior therapy: A subgroup analysis of the randomized phase 3 ASPIRE and ENDEAVOR trials. Hematol Oncol. 2018 Apr;36(2):463-470. doi: 10.1002/hon.2499. Epub 2018 Feb 15.

Moreau P, Stewart KA, Dimopoulos M, Siegel D, Facon T, Berenson J, Raje N, Berdeja JG, Orlowski RZ, Yang H, Ma H, Klippel Z, Zahlten-Kumeli A, Mezzi K, Iskander K, Mateos MV. Once-weekly (70 mg/m2 ) vs twice-weekly (56 mg/m2 ) dosing of carfilzomib in patients with relapsed or refractory multiple myeloma: A post hoc analysis of the ENDEAVOR, A.R.R.O.W., and CHAMPION-1 trials. Cancer Med. 2020 May;9(9):2989-2996. doi: 10.1002/cam4.2945. Epub 2020 Feb 28.

Dimopoulos MA, Moreau P, Iida S, Huang SY, Takezako N, Chng WJ, Zahlten-Kumeli A, Sersch MA, Li J, Huang M, Lee JH. Outcomes for Asian patients with multiple myeloma receiving once- or twice-weekly carfilzomib-based therapy: a subgroup analysis of the randomized phase 3 ENDEAVOR and A.R.R.O.W. Trials. Int J Hematol. 2019 Oct;110(4):466-473. doi: 10.1007/s12185-019-02704-z. Epub 2019 Aug 6.

Goldschmidt H, Moreau P, Ludwig H, Niesvizky R, Chng WJ, Joshua D, Weisel K, Spencer A, Orlowski RZ, Feng S, Iskander KS, Dimopoulos MA. Carfilzomib-dexamethasone versus subcutaneous or intravenous bortezomib in relapsed or refractory multiple myeloma: secondary analysis of the phase 3 ENDEAVOR study. Leuk Lymphoma. 2018 Jun;59(6):1364-1374. doi: 10.1080/10428194.2017.1376743. Epub 2017 Sep 22.

Jakubowiak AJ, Houisse I, Majer I, Benedict A, Campioni M, Panjabi S, Ailawadhi S. Cost-effectiveness of carfilzomib plus dexamethasone compared with bortezomib plus dexamethasone for patients with relapsed or refractory multiple myeloma in the United States. Expert Rev Hematol. 2017 Dec;10(12):1107-1119. doi: 10.1080/17474086.2017.1391088.

Weisel K, Mateos MV, Gay F, Delforge M, Cook G, Szabo Z, Desgraz R, DeCosta L, Moreau P. Efficacy and safety profile of deep responders to carfilzomib-based therapy: a subgroup analysis from ASPIRE and ENDEAVOR. Leukemia. 2021 Jun;35(6):1732-1744. doi: 10.1038/s41375-020-01049-5. Epub 2020 Oct 16.

Weisel K, Majer I, DeCosta L, Oriol A, Goldschmidt H, Ludwig H, Campioni M, Szabo Z, Dimopoulos M. Carfilzomib and dexamethasone versus eight cycles of bortezomib and dexamethasone in patients with relapsed or refractory multiple myeloma: an indirect comparison using data from the phase 3 ENDEAVOR and CASTOR trials. Leuk Lymphoma. 2020 Jan;61(1):37-46. doi: 10.1080/10428194.2019.1648806. Epub 2019 Oct 22.

Orlowski RZ, Moreau P, Niesvizky R, Ludwig H, Oriol A, Chng WJ, Goldschmidt H, Yang Z, Kimball AS, Dimopoulos M. Carfilzomib-Dexamethasone Versus Bortezomib-Dexamethasone in Relapsed or Refractory Multiple Myeloma: Updated Overall Survival, Safety, and Subgroups. Clin Lymphoma Myeloma Leuk. 2019 Aug;19(8):522-530.e1. doi: 10.1016/j.clml.2019.04.018. Epub 2019 May 2.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Majer IM, Castaigne JG, Palmer S, DeCosta L, Campioni M. Modeling Covariate-Adjusted Survival for Economic Evaluations in Oncology. Pharmacoeconomics. 2019 May;37(5):727-737. doi: 10.1007/s40273-018-0759-6.

Rosenthal A, Luthi J, Belohlavek M, Kortum KM, Mookadam F, Mayo A, Fonseca R, Bergsagel PL, Reeder CB, Mikhael JR, Stewart AK. Carfilzomib and the cardiorenal system in myeloma: an endothelial effect? Blood Cancer J. 2016 Jan 15;6(1):e384. doi: 10.1038/bcj.2015.112.

Dimopoulos MA, Moreau P, Palumbo A, Joshua D, Pour L, Hajek R, Facon T, Ludwig H, Oriol A, Goldschmidt H, Rosinol L, Straub J, Suvorov A, Araujo C, Rimashevskaya E, Pika T, Gaidano G, Weisel K, Goranova-Marinova V, Schwarer A, Minuk L, Masszi T, Karamanesht I, Offidani M, Hungria V, Spencer A, Orlowski RZ, Gillenwater HH, Mohamed N, Feng S, Chng WJ; ENDEAVOR Investigators. Carfilzomib and dexamethasone versus bortezomib and dexamethasone for patients with relapsed or refractory multiple myeloma (ENDEAVOR): a randomised, phase 3, open-label, multicentre study. Lancet Oncol. 2016 Jan;17(1):27-38. doi: 10.1016/S1470-2045(15)00464-7. Epub 2015 Dec 5.

Layout table for additonal information

Responsible Party:	Amgen
ClinicalTrials.gov Identifier:	NCT01568866
Other Study ID Numbers:	2011-003 2012-000128-16 ( EudraCT Number )
First Submitted:	March 28, 2012
First Posted:	April 2, 2012
Results First Submitted:	November 6, 2015
Results First Posted:	December 11, 2015
Last Update Posted:	November 14, 2022

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