Trial Outcomes & Findings for Evaluate Risk/Benefit of Nab Paclitaxel in Combination With Gemcitabine and Carboplatin Compared to Gemcitabine and Carboplatin in Triple Negative Metastatic Breast Cancer (or Metastatic Triple Negative Breast Cancer) (NCT NCT01881230)

Last Updated: 2019-02-21

Results Overview

PFS was defined as the time from the date of randomization to the date of disease progression or death from any cause on or prior to the data cutoff date for the statistical analysis, whichever occurred earlier. Tumor responses were assessed every 6 weeks using, Response Evaluation Criteria in Solid Tumors (RECIST 1.1) and defined as: Complete response (CR) is the disappearance of all target lesions; Partial response (PR) occurs when at least a 30% decrease in the sum of diameters of target lesions from baseline; Stable disease is neither sufficient shrinkage to qualify for a PR nor sufficient increase of lesions to qualify for Progressive disease (PD); Progressive Disease- is at least a 20% increase in the sum of diameters of target lesions from nadir.

Recruitment status

COMPLETED

Study phase

PHASE2/PHASE3

Target enrollment

191 participants

Primary outcome timeframe

From date of randomization to data cut-off date of 16 December 2016; total length of time on study was 31 months for Arm A, 34 months for Arm B and 35 months for Arm C

Results posted on

2019-02-21

Participant Flow

This multicenter study was conducted by investigators in 11 countries in North America, Europe, Australia and South America, and enrolled participants at a total of 86 sites. Due to changes in the treatment landscape since the initiation of this trial, the decision was made not to proceed to the Phase 3 portion of the study.

Participants were randomized 1:1:1, stratified by disease free interval (≤ 1 year; \> 1 year).

Participant milestones

Participant milestones
Measure	Arm A: Nab-Paclitaxel Plus (+) Gemcitabine Participants received nab-Paclitaxel 125 mg/m\^2 on Days 1 and 8 by intravenous (IV) administration followed by gemcitabine 1000 mg/m\^2 on Days 1 and 8 by IV administration in each 21-day treatment cycle. Participants continued treatment until progressive disease (PD), unacceptable toxicity, required palliative radiotherapy or surgical intervention of lesion(s), withdrawal from study treatment, withdrawal of study consent, participant refusal or the investigator felt it was no longer in the best interest of the participant to continue on treatment.	Arm B: Nab-Paclitaxel + Carboplatin Participants received nab-Paclitaxel 125 mg/m\^2 on Days 1 and 8 by IV administration followed by carboplatin area under the curve 2 (AUC 2) on Days 1 and 8 in each 21-day treatment cycle. Participants continued treatment until progressive disease (PD), unacceptable toxicity, required palliative radiotherapy or surgical intervention of lesion(s), withdrawal from study treatment, withdrawal of study consent, participant refusal or the investigator felt it was no longer in the best interest of the participant to continue on treatment.	Arm C: Gemcitabine + Carboplatin Participants received gemcitabine 1000 mg/m\^2 on Days 1 and 8 by IV administration, followed by carboplatin AUC 2 on Days 1 and 8 by IV administration in each 21-day treatment cycle. Participants continued treatment until progressive disease (PD), unacceptable toxicity, required palliative radiotherapy or surgical intervention of lesion(s), withdrawal from study treatment, withdrawal of study consent, participant refusal or the investigator felt it was no longer in the best interest of the participant to continue on treatment.
Overall Study STARTED	61	64	66
Overall Study Safety Population	60	64	64
Overall Study Treatment Discontinued	60	64	64
Overall Study COMPLETED	0	0	0
Overall Study NOT COMPLETED	61	64	66

Reasons for withdrawal

Reasons for withdrawal
Measure	Arm A: Nab-Paclitaxel Plus (+) Gemcitabine Participants received nab-Paclitaxel 125 mg/m\^2 on Days 1 and 8 by intravenous (IV) administration followed by gemcitabine 1000 mg/m\^2 on Days 1 and 8 by IV administration in each 21-day treatment cycle. Participants continued treatment until progressive disease (PD), unacceptable toxicity, required palliative radiotherapy or surgical intervention of lesion(s), withdrawal from study treatment, withdrawal of study consent, participant refusal or the investigator felt it was no longer in the best interest of the participant to continue on treatment.	Arm B: Nab-Paclitaxel + Carboplatin Participants received nab-Paclitaxel 125 mg/m\^2 on Days 1 and 8 by IV administration followed by carboplatin area under the curve 2 (AUC 2) on Days 1 and 8 in each 21-day treatment cycle. Participants continued treatment until progressive disease (PD), unacceptable toxicity, required palliative radiotherapy or surgical intervention of lesion(s), withdrawal from study treatment, withdrawal of study consent, participant refusal or the investigator felt it was no longer in the best interest of the participant to continue on treatment.	Arm C: Gemcitabine + Carboplatin Participants received gemcitabine 1000 mg/m\^2 on Days 1 and 8 by IV administration, followed by carboplatin AUC 2 on Days 1 and 8 by IV administration in each 21-day treatment cycle. Participants continued treatment until progressive disease (PD), unacceptable toxicity, required palliative radiotherapy or surgical intervention of lesion(s), withdrawal from study treatment, withdrawal of study consent, participant refusal or the investigator felt it was no longer in the best interest of the participant to continue on treatment.
Overall Study Death	2	0	1
Overall Study Adverse Event	9	13	12
Overall Study Progressive Disease	31	35	36
Overall Study Symptomatic Deterioration	3	3	1
Overall Study Withdrawal by Subject	6	4	6
Overall Study Physician Decision	4	3	6
Overall Study Non-Compliance with Study Drug	1	2	0
Overall Study Given Commercially Available Drug	0	0	2
Overall Study Protocol Violation	1	1	0
Overall Study Miscellaneous	3	3	0
Overall Study Untreated: Other	0	0	1
Overall Study Untreated: Death	0	0	1
Overall Study Untreated: Withdrawal Before Study Start	1	0	0

Baseline Characteristics

Evaluate Risk/Benefit of Nab Paclitaxel in Combination With Gemcitabine and Carboplatin Compared to Gemcitabine and Carboplatin in Triple Negative Metastatic Breast Cancer (or Metastatic Triple Negative Breast Cancer)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm A: Nab-Paclitaxel Plus (+) Gemcitabine n=61 Participants Participants received nab-Paclitaxel 125 mg/m\^2 on Days 1 and 8 by intravenous (IV) administration followed by gemcitabine 1000 mg/m\^2 on Days 1 and 8 by IV administration in each 21-day treatment cycle. Participants continued treatment until progressive disease (PD), unacceptable toxicity, required palliative radiotherapy or surgical intervention of lesion(s), withdrawal from study treatment, withdrawal of study consent, participant refusal or the investigator felt it was no longer in the best interest of the participant to continue on treatment.	Arm B: Nab-Paclitaxel + Carboplatin n=64 Participants Participants received nab-Paclitaxel 125 mg/m\^2 on Days 1 and 8 by IV administration followed by carboplatin area under the curve 2 (AUC 2) on Days 1 and 8 in each 21-day treatment cycle. Participants continued treatment until progressive disease (PD), unacceptable toxicity, required palliative radiotherapy or surgical intervention of lesion(s), withdrawal from study treatment, withdrawal of study consent, participant refusal or the investigator felt it was no longer in the best interest of the participant to continue on treatment.	Arm C: Gemcitabine + Carboplatin n=66 Participants Participants received gemcitabine 1000 mg/m\^2 on Days 1 and 8 by IV administration, followed by carboplatin AUC 2 on Days 1 and 8 by IV administration in each 21-day treatment cycle. Participants continued treatment until progressive disease (PD), unacceptable toxicity, required palliative radiotherapy or surgical intervention of lesion(s), withdrawal from study treatment, withdrawal of study consent, participant refusal or the investigator felt it was no longer in the best interest of the participant to continue on treatment.	Total n=191 Participants Total of all reporting groups
Age, Continuous	53.7 years STANDARD_DEVIATION 12.16 • n=5 Participants	54.3 years STANDARD_DEVIATION 11.96 • n=7 Participants	56.7 years STANDARD_DEVIATION 10.87 • n=5 Participants	54.9 years STANDARD_DEVIATION 11.67 • n=4 Participants
Sex: Female, Male Female	61 Participants n=5 Participants	64 Participants n=7 Participants	66 Participants n=5 Participants	191 Participants n=4 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race Black or African American	9 Participants n=5 Participants	6 Participants n=7 Participants	8 Participants n=5 Participants	23 Participants n=4 Participants
Race White	50 Participants n=5 Participants	55 Participants n=7 Participants	54 Participants n=5 Participants	159 Participants n=4 Participants
Race Unknown or Not Reported	2 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants	9 Participants n=4 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 0 = Fully Active	34 Participants n=5 Participants	38 Participants n=7 Participants	42 Participants n=5 Participants	114 Participants n=4 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 1 = Restrictive but ambulatory	25 Participants n=5 Participants	26 Participants n=7 Participants	22 Participants n=5 Participants	73 Participants n=4 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 2 = Ambulatory but unable to work	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status Missing	1 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	3 Participants n=4 Participants
Disease Free Interval by Clinical Interpretation ≤ 1 year	17 Years n=5 Participants	16 Years n=7 Participants	20 Years n=5 Participants	53 Years n=4 Participants
Disease Free Interval by Clinical Interpretation > 1 year	43 Years n=5 Participants	48 Years n=7 Participants	45 Years n=5 Participants	136 Years n=4 Participants
Disease Free Interval by Clinical Interpretation Missing	1 Years n=5 Participants	0 Years n=7 Participants	1 Years n=5 Participants	2 Years n=4 Participants
Time from Diagnosis to First Documented Disease/Relapse	38.8 months STANDARD_DEVIATION 49.46 • n=5 Participants	29.9 months STANDARD_DEVIATION 37.18 • n=7 Participants	50.9 months STANDARD_DEVIATION 62.60 • n=5 Participants	40.0 months STANDARD_DEVIATION 51.46 • n=4 Participants
Time from First Documented Metastatic Disease/Relapse to Study Randomization	2.1 months STANDARD_DEVIATION 5.08 • n=5 Participants	4.2 months STANDARD_DEVIATION 18.39 • n=7 Participants	1.6 months STANDARD_DEVIATION 1.70 • n=5 Participants	2.6 months STANDARD_DEVIATION 11.07 • n=4 Participants
Time from Primary Diagnosis to Randomization	43.7 months STANDARD_DEVIATION 54.60 • n=5 Participants	35.5 months STANDARD_DEVIATION 40.51 • n=7 Participants	52.5 months STANDARD_DEVIATION 62.37 • n=5 Participants	44.0 months STANDARD_DEVIATION 53.53 • n=4 Participants
Current Sites of Metastasis Lymph Nodes(s)	38 participants n=5 Participants	50 participants n=7 Participants	51 participants n=5 Participants	139 participants n=4 Participants
Current Sites of Metastasis Lung/Thoracic	42 participants n=5 Participants	42 participants n=7 Participants	41 participants n=5 Participants	125 participants n=4 Participants
Current Sites of Metastasis Bone	23 participants n=5 Participants	21 participants n=7 Participants	25 participants n=5 Participants	69 participants n=4 Participants
Current Sites of Metastasis Liver	17 participants n=5 Participants	16 participants n=7 Participants	23 participants n=5 Participants	56 participants n=4 Participants
Current Sites of Metastasis Right/Left Breast	15 participants n=5 Participants	19 participants n=7 Participants	17 participants n=5 Participants	51 participants n=4 Participants
Current Sites of Metastasis Skin/Soft Tissue	13 participants n=5 Participants	13 participants n=7 Participants	8 participants n=5 Participants	34 participants n=4 Participants
Current Sites of Metastasis Other	13 participants n=5 Participants	10 participants n=7 Participants	8 participants n=5 Participants	31 participants n=4 Participants
Current Sites of Metastasis Abdomen/Peritoneal	1 participants n=5 Participants	2 participants n=7 Participants	3 participants n=5 Participants	6 participants n=4 Participants
Stage of Primary Diagnosis Stage 0	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Stage of Primary Diagnosis Stage IA	7 Participants n=5 Participants	6 Participants n=7 Participants	11 Participants n=5 Participants	24 Participants n=4 Participants
Stage of Primary Diagnosis Stage IB	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Stage of Primary Diagnosis Stage IIA	14 Participants n=5 Participants	9 Participants n=7 Participants	15 Participants n=5 Participants	38 Participants n=4 Participants
Stage of Primary Diagnosis Stage IIB	8 Participants n=5 Participants	7 Participants n=7 Participants	9 Participants n=5 Participants	24 Participants n=4 Participants
Stage of Primary Diagnosis Stage IIIA	9 Participants n=5 Participants	10 Participants n=7 Participants	3 Participants n=5 Participants	22 Participants n=4 Participants
Stage of Primary Diagnosis Stage IIIB	3 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants	11 Participants n=4 Participants
Stage of Primary Diagnosis Stage IIIC	3 Participants n=5 Participants	3 Participants n=7 Participants	2 Participants n=5 Participants	8 Participants n=4 Participants
Stage of Primary Diagnosis Stage IV	11 Participants n=5 Participants	17 Participants n=7 Participants	10 Participants n=5 Participants	38 Participants n=4 Participants
Triple-Negative Breast Cancer (TNBC) at Primary Diagnosis	51 Participants n=5 Participants	53 Participants n=7 Participants	48 Participants n=5 Participants	152 Participants n=4 Participants
Triple-Negative at Latest Diagnosis	60 Participants n=5 Participants	62 Participants n=7 Participants	65 Participants n=5 Participants	187 Participants n=4 Participants

PRIMARY outcome

Timeframe: From date of randomization to data cut-off date of 16 December 2016; total length of time on study was 31 months for Arm A, 34 months for Arm B and 35 months for Arm C

Population: ITT includes all randomized participants regardless of whether they received any IP or had any efficacy assessments collected. Those who did not have disease progression or had not died as of the data cutoff date were censored at the time of the last radiologic assessment prior to the data cutoff date.

Outcome measures

Outcome measures
Measure	Arm A: Nab-Paclitaxel + Gemcitabine n=61 Participants Participants received nab-Paclitaxel 125 mg/m\^2 on Days 1 and 8 by intravenous (IV) administration followed by gemcitabine 1000 mg/m\^2 on Days 1 and 8 by IV administration of each 21-day treatment cycle. Participants continued treatment until progressive disease (PD), unacceptable toxicity, required palliative radiotherapy or surgical intervention of lesion(s), withdrawal from study treatment, withdrawal of study consent, participant refusal or the investigator felt it was no longer in the best interest of the participant to continue on treatment	Arm B: Nab-Paclitaxel + Carboplatin n=64 Participants Participants received nab-Paclitaxel 125 mg/m\^2 on Days 1 and 8 by IV administration followed by carboplatin area under the curve 2 (AUC 2) on Days 1 and 8 in each 21-day treatment cycle. Participants continued treatment until progressive disease (PD), unacceptable toxicity, required palliative radiotherapy or surgical intervention of lesion(s), withdrawal from study treatment, withdrawal of study consent, participant refusal or the investigator felt it was no longer in the best interest of the participant to continue on treatment.	Arm C: Gemcitabine + Carboplatin n=66 Participants Participants received gemcitabine 1000 mg/m\^2 on Days 1 and 8 by IV administration, followed by carboplatin AUC 2 on Days 1 and 8 by IV administration in each 21-day treatment cycle. Participants continued treatment until progressive disease (PD), unacceptable toxicity, required palliative radiotherapy or surgical intervention of lesion(s), withdrawal from study treatment, withdrawal of study consent, participant refusal or the investigator felt it was no longer in the best interest of the participant to continue on treatment.
Kaplan-Meier Estimates of Progression-Free Survival (PFS) Based on Investigator Assessment.	5.5 months Interval 4.1 to 7.0	8.3 months Interval 5.7 to 10.6	6.0 months Interval 4.7 to 7.2

SECONDARY outcome

Timeframe: Disease response was assessed every 6 weeks; from date of randomization to data cut-off date of 16 December 2016; total length of time on study was 31 months for Arm A, 34 months for Arm B and 35 months for Arm C

Percentage of participants with an Objective Complete or Partial Overall Response according to RECIST 1.1 and defined as: Complete response-disappearance of all target lesions; partial response at least a 30% decrease in the sum of diameters of target lesions from baseline; stable disease-neither sufficient shrinkage to qualify for PR nor sufficient increase of lesions to qualify for Progressive disease (PD)• Progressive Disease- At least a 20% increase in the sum of diameters of target lesions from nadir.

Outcome measures

Outcome measures
Measure	Arm A: Nab-Paclitaxel + Gemcitabine n=61 Participants Participants received nab-Paclitaxel 125 mg/m\^2 on Days 1 and 8 by intravenous (IV) administration followed by gemcitabine 1000 mg/m\^2 on Days 1 and 8 by IV administration of each 21-day treatment cycle. Participants continued treatment until progressive disease (PD), unacceptable toxicity, required palliative radiotherapy or surgical intervention of lesion(s), withdrawal from study treatment, withdrawal of study consent, participant refusal or the investigator felt it was no longer in the best interest of the participant to continue on treatment	Arm B: Nab-Paclitaxel + Carboplatin n=64 Participants Participants received nab-Paclitaxel 125 mg/m\^2 on Days 1 and 8 by IV administration followed by carboplatin area under the curve 2 (AUC 2) on Days 1 and 8 in each 21-day treatment cycle. Participants continued treatment until progressive disease (PD), unacceptable toxicity, required palliative radiotherapy or surgical intervention of lesion(s), withdrawal from study treatment, withdrawal of study consent, participant refusal or the investigator felt it was no longer in the best interest of the participant to continue on treatment.	Arm C: Gemcitabine + Carboplatin n=66 Participants Participants received gemcitabine 1000 mg/m\^2 on Days 1 and 8 by IV administration, followed by carboplatin AUC 2 on Days 1 and 8 by IV administration in each 21-day treatment cycle. Participants continued treatment until progressive disease (PD), unacceptable toxicity, required palliative radiotherapy or surgical intervention of lesion(s), withdrawal from study treatment, withdrawal of study consent, participant refusal or the investigator felt it was no longer in the best interest of the participant to continue on treatment.
Percentage of Participants With an Objective Complete or Partial Overall Response by Investigator Assessment.	39.3 percentage of participants Interval 27.1 to 52.7	73.4 percentage of participants Interval 60.9 to 83.7	43.9 percentage of participants Interval 31.7 to 56.7

SECONDARY outcome

Timeframe: Cycle 6

The percentage of participants who initiated Cycle 6 receiving doublet combination therapy regardless of the need for dose modifications.

Outcome measures

Outcome measures
Measure	Arm A: Nab-Paclitaxel + Gemcitabine n=61 Participants Participants received nab-Paclitaxel 125 mg/m\^2 on Days 1 and 8 by intravenous (IV) administration followed by gemcitabine 1000 mg/m\^2 on Days 1 and 8 by IV administration of each 21-day treatment cycle. Participants continued treatment until progressive disease (PD), unacceptable toxicity, required palliative radiotherapy or surgical intervention of lesion(s), withdrawal from study treatment, withdrawal of study consent, participant refusal or the investigator felt it was no longer in the best interest of the participant to continue on treatment	Arm B: Nab-Paclitaxel + Carboplatin n=64 Participants Participants received nab-Paclitaxel 125 mg/m\^2 on Days 1 and 8 by IV administration followed by carboplatin area under the curve 2 (AUC 2) on Days 1 and 8 in each 21-day treatment cycle. Participants continued treatment until progressive disease (PD), unacceptable toxicity, required palliative radiotherapy or surgical intervention of lesion(s), withdrawal from study treatment, withdrawal of study consent, participant refusal or the investigator felt it was no longer in the best interest of the participant to continue on treatment.	Arm C: Gemcitabine + Carboplatin n=66 Participants Participants received gemcitabine 1000 mg/m\^2 on Days 1 and 8 by IV administration, followed by carboplatin AUC 2 on Days 1 and 8 by IV administration in each 21-day treatment cycle. Participants continued treatment until progressive disease (PD), unacceptable toxicity, required palliative radiotherapy or surgical intervention of lesion(s), withdrawal from study treatment, withdrawal of study consent, participant refusal or the investigator felt it was no longer in the best interest of the participant to continue on treatment.
Percentage of Participants Who Initiated Cycle 6 Receiving Doublet Combination Therapy	55.7 percentage of participants Interval 42.5 to 68.5	64.1 percentage of participants Interval 51.1 to 75.7	50.0 percentage of participants Interval 37.4 to 62.6

SECONDARY outcome

Timeframe: From date of randomization to data cut-off date of 16 December 2016; total length of time on study was 31 months for Arm A, 34 months for Arm B and 35 months for Arm C

Population: The ITT population includes all randomized participants regardless of whether the participant received any Investigational Product (IP) or had any efficacy assessments collected.

Overall survival was defined as the time from the date of randomization to the date of death (from any cause).

Outcome measures

Outcome measures
Measure	Arm A: Nab-Paclitaxel + Gemcitabine n=61 Participants Participants received nab-Paclitaxel 125 mg/m\^2 on Days 1 and 8 by intravenous (IV) administration followed by gemcitabine 1000 mg/m\^2 on Days 1 and 8 by IV administration of each 21-day treatment cycle. Participants continued treatment until progressive disease (PD), unacceptable toxicity, required palliative radiotherapy or surgical intervention of lesion(s), withdrawal from study treatment, withdrawal of study consent, participant refusal or the investigator felt it was no longer in the best interest of the participant to continue on treatment	Arm B: Nab-Paclitaxel + Carboplatin n=64 Participants Participants received nab-Paclitaxel 125 mg/m\^2 on Days 1 and 8 by IV administration followed by carboplatin area under the curve 2 (AUC 2) on Days 1 and 8 in each 21-day treatment cycle. Participants continued treatment until progressive disease (PD), unacceptable toxicity, required palliative radiotherapy or surgical intervention of lesion(s), withdrawal from study treatment, withdrawal of study consent, participant refusal or the investigator felt it was no longer in the best interest of the participant to continue on treatment.	Arm C: Gemcitabine + Carboplatin n=66 Participants Participants received gemcitabine 1000 mg/m\^2 on Days 1 and 8 by IV administration, followed by carboplatin AUC 2 on Days 1 and 8 by IV administration in each 21-day treatment cycle. Participants continued treatment until progressive disease (PD), unacceptable toxicity, required palliative radiotherapy or surgical intervention of lesion(s), withdrawal from study treatment, withdrawal of study consent, participant refusal or the investigator felt it was no longer in the best interest of the participant to continue on treatment.
Kaplan-Meier Estimates of Overall Survival	12.1 months Interval 9.4 to 15.9	16.8 months Interval 11.3 to 20.6	12.6 months Interval 10.1 to 16.6

SECONDARY outcome

Timeframe: From randomization through to 28 days after the last dose of IP; up to data cut off date of 16 Dec 2016; maximum treatment duration of study drug exposure was 108.3 weeks for Arm A, 83 weeks for Arm B, 110.1 weeks for Arm C

Population: The safety population includes all randomized participants who received at least 1 dose of IP.

Treatment-emergent adverse events (TEAEs) were defined as any AEs that began or worsened with the onset date on or after the date of the first dose of IP through 28 days after the last dose. A serious AE (SAE) = any AE which results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; constitutes an important medical event. The severity of AEs was graded based on the participant's symptoms according to the Common Terminology Criteria for Adverse Events (CTCAE, Version 4.0); AEs were evaluated for severity as follows: Grade 1 = Mild - transient or mild discomfort; no medical intervention required; Grade 2 = Moderate - mild to moderate limitation in activity; Grade 3 = Severe; Grade 4 = Life threatening; Grade 5 = Death.

Outcome measures

Outcome measures
Measure	Arm A: Nab-Paclitaxel + Gemcitabine n=60 Participants Participants received nab-Paclitaxel 125 mg/m\^2 on Days 1 and 8 by intravenous (IV) administration followed by gemcitabine 1000 mg/m\^2 on Days 1 and 8 by IV administration of each 21-day treatment cycle. Participants continued treatment until progressive disease (PD), unacceptable toxicity, required palliative radiotherapy or surgical intervention of lesion(s), withdrawal from study treatment, withdrawal of study consent, participant refusal or the investigator felt it was no longer in the best interest of the participant to continue on treatment	Arm B: Nab-Paclitaxel + Carboplatin n=64 Participants Participants received nab-Paclitaxel 125 mg/m\^2 on Days 1 and 8 by IV administration followed by carboplatin area under the curve 2 (AUC 2) on Days 1 and 8 in each 21-day treatment cycle. Participants continued treatment until progressive disease (PD), unacceptable toxicity, required palliative radiotherapy or surgical intervention of lesion(s), withdrawal from study treatment, withdrawal of study consent, participant refusal or the investigator felt it was no longer in the best interest of the participant to continue on treatment.	Arm C: Gemcitabine + Carboplatin n=64 Participants Participants received gemcitabine 1000 mg/m\^2 on Days 1 and 8 by IV administration, followed by carboplatin AUC 2 on Days 1 and 8 by IV administration in each 21-day treatment cycle. Participants continued treatment until progressive disease (PD), unacceptable toxicity, required palliative radiotherapy or surgical intervention of lesion(s), withdrawal from study treatment, withdrawal of study consent, participant refusal or the investigator felt it was no longer in the best interest of the participant to continue on treatment.
Number of Participants With Treatment Emergent Adverse Events (TEAEs) Any TEAE	60 participants	63 participants	64 participants
Number of Participants With Treatment Emergent Adverse Events (TEAEs) Any Grade 3 or Higher TEAE	46 participants	51 participants	54 participants
Number of Participants With Treatment Emergent Adverse Events (TEAEs) Treatment-related TEAE	59 participants	62 participants	60 participants
Number of Participants With Treatment Emergent Adverse Events (TEAEs) Treatment-related, Grade 3 or Higher TEAE	35 participants	43 participants	46 participants
Number of Participants With Treatment Emergent Adverse Events (TEAEs) Serious TEAE	22 participants	20 participants	25 participants
Number of Participants With Treatment Emergent Adverse Events (TEAEs) Treatment-related Serious TEAE	10 participants	9 participants	13 participants
Number of Participants With Treatment Emergent Adverse Events (TEAEs) TEAE Leading to Discontinuation (D/C) of IP	16 participants	29 participants	15 participants
Number of Participants With Treatment Emergent Adverse Events (TEAEs) Treatment Related (TR) TEAE Leading to D/C of IP	12 participants	27 participants	12 participants
Number of Participants With Treatment Emergent Adverse Events (TEAEs) TEAE Leading to Dose Reduction (DR) of IP	23 participants	20 participants	25 participants
Number of Participants With Treatment Emergent Adverse Events (TEAEs) Treatment related TEAE Leading to DR of IP	23 participants	20 participants	23 participants
Number of Participants With Treatment Emergent Adverse Events (TEAEs) TEAE Leading to Dose Interruption (DI) of IP	31 participants	50 participants	50 participants
Number of Participants With Treatment Emergent Adverse Events (TEAEs) TR TEAE Leading to DI of IP	27 participants	44 participants	44 participants
Number of Participants With Treatment Emergent Adverse Events (TEAEs) TEAE leading to D/C of nab-Paclitaxel	16 participants	17 participants	0 participants
Number of Participants With Treatment Emergent Adverse Events (TEAEs) TR TEAE leading to D/C of nab-Paclitaxel	11 participants	13 participants	0 participants
Number of Participants With Treatment Emergent Adverse Events (TEAEs) TEAE leading to DR of nab-Paclitaxel	22 participants	19 participants	0 participants
Number of Participants With Treatment Emergent Adverse Events (TEAEs) TR TEAE leading to DR of nab-Paclitaxel	21 participants	19 participants	0 participants
Number of Participants With Treatment Emergent Adverse Events (TEAEs) TEAE leading to DI of nab-Paclitaxel	31 participants	50 participants	0 participants
Number of Participants With Treatment Emergent Adverse Events (TEAEs) TR TEAE leading to DI of nab-Paclitaxel	27 participants	44 participants	0 participants
Number of Participants With Treatment Emergent Adverse Events (TEAEs) TEAE leading to D/C of Gemcitabine	13 participants	0 participants	13 participants
Number of Participants With Treatment Emergent Adverse Events (TEAEs) TR TEAE leading to D/C of Gemcitabine	7 participants	0 participants	9 participants
Number of Participants With Treatment Emergent Adverse Events (TEAEs) TEAE leading to DR of Gemcitabine	18 participants	0 participants	25 participants
Number of Participants With Treatment Emergent Adverse Events (TEAEs) TR TEAE leading to DR of Gemcitabine	18 participants	0 participants	23 participants
Number of Participants With Treatment Emergent Adverse Events (TEAEs) TEAE leading to DI of Gemcitabine	31 participants	0 participants	49 participants
Number of Participants With Treatment Emergent Adverse Events (TEAEs) TR TEAE leading to DI of Gemcitabine	24 participants	0 participants	43 participants
Number of Participants With Treatment Emergent Adverse Events (TEAEs) TEAE leading to D/C of Carboplatin	0 participants	28 participants	15 participants
Number of Participants With Treatment Emergent Adverse Events (TEAEs) TR TEAE leading to D/C of Carboplatin	0 participants	25 participants	12 participants
Number of Participants With Treatment Emergent Adverse Events (TEAEs) TEAE leading to DR of Carboplatin	0 participants	17 participants	21 participants
Number of Participants With Treatment Emergent Adverse Events (TEAEs) TR TEAE leading to DR of Carboplatin	0 participants	17 participants	20 participants
Number of Participants With Treatment Emergent Adverse Events (TEAEs) TEAE leading to DI of Carboplatin	0 participants	50 participants	50 participants
Number of Participants With Treatment Emergent Adverse Events (TEAEs) TR TEAE leading to DI of Carboplatin	0 participants	44 participants	43 participants
Number of Participants With Treatment Emergent Adverse Events (TEAEs) TEAE Leading to Death	2 participants	1 participants	2 participants
Number of Participants With Treatment Emergent Adverse Events (TEAEs) Treatment Related TEAE leading to death	1 participants	0 participants	1 participants

SECONDARY outcome

Timeframe: From randomization through to 28 days after the last dose of IP; up to data-cut off of date of 16 Dec 2016; maximum treatment duration of study drug exposure was 108.3 weeks for Arm A, 83 weeks for Arm B, 110.1 weeks for Arm C

Population: The Safety/Treated population includes all randomized participants who received at least 1 dose of IP.

The number of participants with dose modifications occurring during the treatment period. Dose reductions and interruptions are typically caused by clinically significant laboratory abnormalities and /or treatment emergent adverse events/toxicities.

Outcome measures

Outcome measures
Measure	Arm A: Nab-Paclitaxel + Gemcitabine n=60 Participants Participants received nab-Paclitaxel 125 mg/m\^2 on Days 1 and 8 by intravenous (IV) administration followed by gemcitabine 1000 mg/m\^2 on Days 1 and 8 by IV administration of each 21-day treatment cycle. Participants continued treatment until progressive disease (PD), unacceptable toxicity, required palliative radiotherapy or surgical intervention of lesion(s), withdrawal from study treatment, withdrawal of study consent, participant refusal or the investigator felt it was no longer in the best interest of the participant to continue on treatment	Arm B: Nab-Paclitaxel + Carboplatin n=64 Participants Participants received nab-Paclitaxel 125 mg/m\^2 on Days 1 and 8 by IV administration followed by carboplatin area under the curve 2 (AUC 2) on Days 1 and 8 in each 21-day treatment cycle. Participants continued treatment until progressive disease (PD), unacceptable toxicity, required palliative radiotherapy or surgical intervention of lesion(s), withdrawal from study treatment, withdrawal of study consent, participant refusal or the investigator felt it was no longer in the best interest of the participant to continue on treatment.	Arm C: Gemcitabine + Carboplatin n=64 Participants Participants received gemcitabine 1000 mg/m\^2 on Days 1 and 8 by IV administration, followed by carboplatin AUC 2 on Days 1 and 8 by IV administration in each 21-day treatment cycle. Participants continued treatment until progressive disease (PD), unacceptable toxicity, required palliative radiotherapy or surgical intervention of lesion(s), withdrawal from study treatment, withdrawal of study consent, participant refusal or the investigator felt it was no longer in the best interest of the participant to continue on treatment.
Percentage of Participants Experiencing Dose Modifications (Reductions and Interruptions) ≥ one DR for both IPs	33.3 percentage of participants	46.9 percentage of participants	51.6 percentage of participants
Percentage of Participants Experiencing Dose Modifications (Reductions and Interruptions) ≥ one DI for both IPs	38.3 percentage of participants	70.3 percentage of participants	73.4 percentage of participants
Percentage of Participants Experiencing Dose Modifications (Reductions and Interruptions) ≥ one dose missed for both IPs	48.3 percentage of participants	45.3 percentage of participants	56.3 percentage of participants

SECONDARY outcome

Population: The Safety/Treated population includes all randomized participants who received at least 1 dose of IP.

Treatment-emergent adverse events (TEAEs) were defined as any AEs that begin or worsen with an onset date on or after the date of the first dose of IP through 28 days after the last dose.

Outcome measures

Outcome measures
Measure	Arm A: Nab-Paclitaxel + Gemcitabine n=60 Participants Participants received nab-Paclitaxel 125 mg/m\^2 on Days 1 and 8 by intravenous (IV) administration followed by gemcitabine 1000 mg/m\^2 on Days 1 and 8 by IV administration of each 21-day treatment cycle. Participants continued treatment until progressive disease (PD), unacceptable toxicity, required palliative radiotherapy or surgical intervention of lesion(s), withdrawal from study treatment, withdrawal of study consent, participant refusal or the investigator felt it was no longer in the best interest of the participant to continue on treatment	Arm B: Nab-Paclitaxel + Carboplatin n=64 Participants Participants received nab-Paclitaxel 125 mg/m\^2 on Days 1 and 8 by IV administration followed by carboplatin area under the curve 2 (AUC 2) on Days 1 and 8 in each 21-day treatment cycle. Participants continued treatment until progressive disease (PD), unacceptable toxicity, required palliative radiotherapy or surgical intervention of lesion(s), withdrawal from study treatment, withdrawal of study consent, participant refusal or the investigator felt it was no longer in the best interest of the participant to continue on treatment.	Arm C: Gemcitabine + Carboplatin n=64 Participants Participants received gemcitabine 1000 mg/m\^2 on Days 1 and 8 by IV administration, followed by carboplatin AUC 2 on Days 1 and 8 by IV administration in each 21-day treatment cycle. Participants continued treatment until progressive disease (PD), unacceptable toxicity, required palliative radiotherapy or surgical intervention of lesion(s), withdrawal from study treatment, withdrawal of study consent, participant refusal or the investigator felt it was no longer in the best interest of the participant to continue on treatment.
Percentage of Participants Who Discontinued From All Study Treatment Due to TEAEs	21.7 percentage of participants Interval 12.1 to 34.2	26.6 percentage of participants Interval 16.3 to 39.1	21.9 percentage of participants Interval 12.5 to 34.0

Adverse Events

Arm A: Nab-Paclitaxel + Gemcitabine

Serious events: 22 serious events

Other events: 59 other events

Deaths: 0 deaths

Arm B: Nab-Paclitaxel + Carboplatin

Serious events: 20 serious events

Other events: 63 other events

Deaths: 0 deaths

Arm C: Gemcitabine + Carboplatin

Serious events: 25 serious events

Other events: 62 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Anne McClain, Senior Manager Clinical Trial Disclosure

Celgene

Phone: 888-260-1599

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Results from a center cannot be submitted for publication before results of multicenter study are published unless it is more than 12 months since study completion. Then, Investigator can publish if manuscript is submitted to Celgene 60 days prior to submission. If Celgene decides publication would hinder drug development, Investigator must delay submission for 90 more days. Investigator must delete confidential information before submission or defer publication to permit patent applications.
Publication restrictions are in place

Restriction type: OTHER