Trial Outcomes & Findings for Optimal Sequencing of Pembrolizumab (MK-3475) and Standard Platinum-based Chemotherapy in First-Line NSCLC (NCT NCT02591615)

Last Updated: 2022-12-28

Results Overview

The primary objective of this randomized phase II trial to determine the overall response rate (ORR per RECIST 1.1) in Chemotherapy naive patients with stage IV NSCLC after the administration of standard platinum-based chemotherapy before MK-3475 (arm A) and administration of MK-3475 administered before standard platinum-based chemotherapy (arm B). Overall Response (OR) = CR + PR.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

91 participants

Primary outcome timeframe

18 Months

Results posted on

2022-12-28

Participant Flow

Participant milestones

Participant milestones
Measure	Arm A Squamous Carcinoma (Platinum Doublet, Then MK-3475, Then Maintenance MK-3475) For Squamous Carcinoma\> \> Carboplatin AUC = 6 IV day 1 every 21-days for up to 4 cycles\> \> Paclitaxel 200 mg/m2 IV day 1 every 21-days for up to 4 cycles\> \> \> \> Carboplatin: Dose frequency of Q3W, Day 1 of each cycle (standard Chemotherapy)\> \> \> \> Paclitaxel: Dose frequency of Q3W, Day 1 of each cycle (standard Chemotherapy)\> \> \> \> Pemetrexed: Dose frequency of Q3W, Day 1 of each cycle (standard Chemotherapy)	Arm A Non-squamous Carcinoma (Platinum Doublet, Then MK-3475, Then Maintenance MK-3475) For Non-squamous Carcinoma\> \> Carboplatin AUC = 6 IV day 1 every 21-days for up to 4 cycles\> \> Pemetrexed 500 mg/m2 IV day 1 every 21-days for up to 4 cycles\> \> Carboplatin: Dose frequency of Q3W, Day 1 of each cycle (standard Chemotherapy)\> \> Paclitaxel: Dose frequency of Q3W, Day 1 of each cycle (standard Chemotherapy)\> \> Pemetrexed: Dose frequency of Q3W, Day 1 of each cycle (standard Chemotherapy)	Arm B Squamous Carcinoma (Pembro, Then MK-3475, Then Platinum Doublet, Then Maintenance MK-3475) For Squamous Carcinoma:\> \> Carboplatin AUC = 6 IV day 1 every 21-days for up to 4 cycles\> \> Paclitaxel 200 mg/m2 IV day 1 every 21-days for up to 4 cycles\> \> Carboplatin: Dose frequency of Q3W, Day 1 of each cycle (standard Chemotherapy)\> \> \> Paclitaxel: Dose frequency of Q3W, Day 1 of each cycle (standard Chemotherapy)\> \> Pemetrexed: Dose frequency of Q3W, Day 1 of each cycle (standard Chemotherapy)	Arm B Non-squamous Carcinoma (Pembro, Then MK-3475, Then Platinum Doublet, Then Maintenance MK-3475) For Non-squamous Carcinoma\> \> Carboplatin AUC = 6 IV day 1 every 21-days for up to 4 cycles\> \> Pemetrexed 500 mg/m2 IV day 1 every 21-days for up to 4 cycles\> \> MK-3475: Dose frequency of Q3W, Day 1 of each cycle\> \> Carboplatin: Dose frequency of Q3W, Day 1 of each cycle (standard Chemotherapy)\> \> Paclitaxel: Dose frequency of Q3W, Day 1 of each cycle (standard Chemotherapy)\> \> Pemetrexed: Dose frequency of Q3W, Day 1 of each cycle (standard Chemotherapy)
Arm B Pembro Lead in Phase STARTED	9	34	11	37
Arm B Pembro Lead in Phase COMPLETED	9	34	10	37
Arm B Pembro Lead in Phase NOT COMPLETED	0	0	1	0
Platinum Doublet Arm A, MK-3475 Arm B STARTED	9	34	10	37
Platinum Doublet Arm A, MK-3475 Arm B COMPLETED	4	25	6	20
Platinum Doublet Arm A, MK-3475 Arm B NOT COMPLETED	5	9	4	17
MK-3475 Arm A, Platinum Doublet Arm B STARTED	4	25	6	20
MK-3475 Arm A, Platinum Doublet Arm B COMPLETED	2	17	4	18
MK-3475 Arm A, Platinum Doublet Arm B NOT COMPLETED	2	8	2	2
Maintenance MK-3475 STARTED	2	17	4	18
Maintenance MK-3475 COMPLETED	0	3	1	7
Maintenance MK-3475 NOT COMPLETED	2	14	3	11

Reasons for withdrawal

Reasons for withdrawal
Measure	Arm A Squamous Carcinoma (Platinum Doublet, Then MK-3475, Then Maintenance MK-3475) For Squamous Carcinoma\> \> Carboplatin AUC = 6 IV day 1 every 21-days for up to 4 cycles\> \> Paclitaxel 200 mg/m2 IV day 1 every 21-days for up to 4 cycles\> \> \> \> Carboplatin: Dose frequency of Q3W, Day 1 of each cycle (standard Chemotherapy)\> \> \> \> Paclitaxel: Dose frequency of Q3W, Day 1 of each cycle (standard Chemotherapy)\> \> \> \> Pemetrexed: Dose frequency of Q3W, Day 1 of each cycle (standard Chemotherapy)	Arm A Non-squamous Carcinoma (Platinum Doublet, Then MK-3475, Then Maintenance MK-3475) For Non-squamous Carcinoma\> \> Carboplatin AUC = 6 IV day 1 every 21-days for up to 4 cycles\> \> Pemetrexed 500 mg/m2 IV day 1 every 21-days for up to 4 cycles\> \> Carboplatin: Dose frequency of Q3W, Day 1 of each cycle (standard Chemotherapy)\> \> Paclitaxel: Dose frequency of Q3W, Day 1 of each cycle (standard Chemotherapy)\> \> Pemetrexed: Dose frequency of Q3W, Day 1 of each cycle (standard Chemotherapy)	Arm B Squamous Carcinoma (Pembro, Then MK-3475, Then Platinum Doublet, Then Maintenance MK-3475) For Squamous Carcinoma:\> \> Carboplatin AUC = 6 IV day 1 every 21-days for up to 4 cycles\> \> Paclitaxel 200 mg/m2 IV day 1 every 21-days for up to 4 cycles\> \> Carboplatin: Dose frequency of Q3W, Day 1 of each cycle (standard Chemotherapy)\> \> \> Paclitaxel: Dose frequency of Q3W, Day 1 of each cycle (standard Chemotherapy)\> \> Pemetrexed: Dose frequency of Q3W, Day 1 of each cycle (standard Chemotherapy)	Arm B Non-squamous Carcinoma (Pembro, Then MK-3475, Then Platinum Doublet, Then Maintenance MK-3475) For Non-squamous Carcinoma\> \> Carboplatin AUC = 6 IV day 1 every 21-days for up to 4 cycles\> \> Pemetrexed 500 mg/m2 IV day 1 every 21-days for up to 4 cycles\> \> MK-3475: Dose frequency of Q3W, Day 1 of each cycle\> \> Carboplatin: Dose frequency of Q3W, Day 1 of each cycle (standard Chemotherapy)\> \> Paclitaxel: Dose frequency of Q3W, Day 1 of each cycle (standard Chemotherapy)\> \> Pemetrexed: Dose frequency of Q3W, Day 1 of each cycle (standard Chemotherapy)
Arm B Pembro Lead in Phase Withdrawal by Subject	0	0	1	0
Platinum Doublet Arm A, MK-3475 Arm B Withdrawal by Subject	0	1	0	0
Platinum Doublet Arm A, MK-3475 Arm B Adverse Event	1	2	0	2
Platinum Doublet Arm A, MK-3475 Arm B Lack of Efficacy	1	3	4	12
Platinum Doublet Arm A, MK-3475 Arm B Death	1	2	0	2
Platinum Doublet Arm A, MK-3475 Arm B Deemed ineligible	0	1	0	0
Platinum Doublet Arm A, MK-3475 Arm B Withdrew to hospice	1	0	0	1
Platinum Doublet Arm A, MK-3475 Arm B Non compliance	1	0	0	0
MK-3475 Arm A, Platinum Doublet Arm B Adverse Event	0	2	0	1
MK-3475 Arm A, Platinum Doublet Arm B Lack of Efficacy	2	6	0	0
MK-3475 Arm A, Platinum Doublet Arm B Death	0	0	1	1
MK-3475 Arm A, Platinum Doublet Arm B Alternative Therapy	0	0	1	0
Maintenance MK-3475 Adverse Event	0	3	1	2
Maintenance MK-3475 Lack of Efficacy	0	9	0	8
Maintenance MK-3475 Death	0	1	1	0
Maintenance MK-3475 Physician discretion	0	0	1	0
Maintenance MK-3475 Withdrew to hospice	0	1	0	0
Maintenance MK-3475 In active treatment	2	0	0	1

Baseline Characteristics

Optimal Sequencing of Pembrolizumab (MK-3475) and Standard Platinum-based Chemotherapy in First-Line NSCLC

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm A Squamous Carcinoma n=9 Participants For Squamous Carcinoma\> \> Carboplatin AUC = 6 IV day 1 every 21-days for up to 4 cycles\> \> Paclitaxel 200 mg/m2 IV day 1 every 21-days for up to 4 cycles\> \> Carboplatin: Dose frequency of Q3W, Day 1 of each cycle (standard Chemotherapy)\> \> Paclitaxel: Dose frequency of Q3W, Day 1 of each cycle (standard Chemotherapy)\> \> Pemetrexed: Dose frequency of Q3W, Day 1 of each cycle (standard Chemotherapy)	Arm A Non-squamous Carcinoma n=34 Participants For Non-squamous Carcinoma\> \> Carboplatin AUC = 6 IV day 1 every 21-days for up to 4 cycles\> \> Pemetrexed 500 mg/m2 IV day 1 every 21-days for up to 4 cycles\> \> Carboplatin: Dose frequency of Q3W, Day 1 of each cycle (standard Chemotherapy)\> \> \>\> Paclitaxel: Dose frequency of Q3W, Day 1 of each cycle (standard Chemotherapy)\> \>\> \> \>\> Pemetrexed: Dose frequency of Q3W, Day 1 of each cycle (standard Chemotherapy)	Arm B Squamous Carcinoma n=11 Participants For Squamous Carcinoma:\> \> Carboplatin AUC = 6 IV day 1 every 21-days for up to 4 cycles\> \> Paclitaxel 200 mg/m2 IV day 1 every 21-days for up to 4 cycles\> \> Carboplatin: Dose frequency of Q3W, Day 1 of each cycle (standard Chemotherapy)\> \> Paclitaxel: Dose frequency of Q3W, Day 1 of each cycle (standard Chemotherapy)\> \> Pemetrexed: Dose frequency of Q3W, Day 1 of each cycle (standard Chemotherapy)	Arm B Non-squamous Carcinoma n=37 Participants For Non-squamous Carcinoma\> \> Carboplatin AUC = 6 IV day 1 every 21-days for up to 4 cycles\> \> Pemetrexed 500 mg/m2 IV day 1 every 21-days for up to 4 cycles\> \> MK-3475: Dose frequency of Q3W, Day 1 of each cycle\> \> Carboplatin: Dose frequency of Q3W, Day 1 of each cycle (standard Chemotherapy)\> \> Paclitaxel: Dose frequency of Q3W, Day 1 of each cycle (standard Chemotherapy)\> \> Pemetrexed: Dose frequency of Q3W, Day 1 of each cycle (standard Chemotherapy)	Total n=91 Participants Total of all reporting groups
Age, Continuous	65 years n=93 Participants	69 years n=4 Participants	67 years n=27 Participants	68 years n=483 Participants	68 years n=36 Participants
Sex: Female, Male Female	2 Participants n=93 Participants	17 Participants n=4 Participants	4 Participants n=27 Participants	20 Participants n=483 Participants	43 Participants n=36 Participants
Sex: Female, Male Male	7 Participants n=93 Participants	17 Participants n=4 Participants	7 Participants n=27 Participants	17 Participants n=483 Participants	48 Participants n=36 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	9 Participants n=93 Participants	34 Participants n=4 Participants	11 Participants n=27 Participants	37 Participants n=483 Participants	91 Participants n=36 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants
Race (NIH/OMB) Asian	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=93 Participants	0 Participants n=4 Participants	1 Participants n=27 Participants	0 Participants n=483 Participants	2 Participants n=36 Participants
Race (NIH/OMB) Black or African American	3 Participants n=93 Participants	1 Participants n=4 Participants	1 Participants n=27 Participants	3 Participants n=483 Participants	8 Participants n=36 Participants
Race (NIH/OMB) White	5 Participants n=93 Participants	33 Participants n=4 Participants	9 Participants n=27 Participants	32 Participants n=483 Participants	79 Participants n=36 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	2 Participants n=483 Participants	2 Participants n=36 Participants

PRIMARY outcome

Timeframe: 18 Months

Population: All patients that started treatment are included in analysis.

Outcome measures

Outcome measures
Measure	Arm A (Both Squamous and Non-Squamous) n=43 Participants For Squamous Carcinoma Carboplatin AUC = 6 IV day 1 every 21-days for up to 4 cycles Paclitaxel 200 mg/m2 IV day 1 every 21-days for up to 4 cycles OR For Non-squamous Carcinoma\> Carboplatin AUC = 6 IV day 1 every 21-days for up to 4 cycles Pemetrexed 500 mg/m2 IV day 1 every 21-days for up to 4 cycles Carboplatin: Dose frequency of Q3W, Day 1 of each cycle (standard Chemotherapy) Paclitaxel: Dose frequency of Q3W, Day 1 of each cycle (standard Chemotherapy) Pemetrexed: Dose frequency of Q3W, Day 1 of each cycle (standard Chemotherapy)	Arm B (Both Squamous and Non-Squamous) n=47 Participants MK-3475 200 mg/m2 IV every 21-days for up to 4 cycles\> \>\> \> \>\> Patients with CR, PR, or SD by irRC will then be treated with:\> \>\> \> \>\> For Squamous Carcinoma:\> \>\> \> \>\> Carboplatin AUC = 6 IV day 1 every 21-days for up to 4 cycles\> \>\> Paclitaxel 200 mg/m2 IV day 1 every 21-days for up to 4 cycles\> \>\> \> \>\> OR\> \>\> \> \>\> For Non-squamous Carcinoma\> \>\> \> \>\> Carboplatin AUC = 6 IV day 1 every 21-days for up to 4 cycles\> \>\> Pemetrexed 500 mg/m2 IV day 1 every 21-days for up to 4 cycles\> \>\> \> \>\> MK-3475: Dose frequency of Q3W, Day 1 of each cycle\> \>\> \> \>\> Carboplatin: Dose frequency of Q3W, Day 1 of each cycle (standard Chemotherapy)\> \>\> \> \>\> Paclitaxel: Dose frequency of Q3W, Day 1 of each cycle (standard Chemotherapy)\> \>\> \> \>\> Pemetrexed: Dose frequency of Q3W, Day 1 of each cycle (standard Chemotherapy)	Arm B Squamous Carcinoma Pemetrexed: Dose frequency of Q3W, Day 1 of each cycle (standard Chemotherapy)	Arm B Non-squamous Carcinoma Pemetrexed: Dose frequency of Q3W, Day 1 of each cycle (standard Chemotherapy)
Overall Response Rate (ORR) Per RECIST 1.1	0.395 proportion of participants Interval 0.249 to 0.541	0.404 proportion of participants Interval 0.264 to 0.545	—	—

SECONDARY outcome

Timeframe: 24 Months

Population: All patients that were treated were included in analysis.

To compare the progression-free survival (PFS) per RECIST 1.1 in previously untreated patients with advanced NSCLC treated with first line carboplatin-based chemotherapy followed by MK-3475 to patients treated with MK-3475 prior to first-line carboplatin-based chemotherapy.

Outcome measures

Outcome measures
Measure	Arm A (Both Squamous and Non-Squamous) n=43 Participants For Squamous Carcinoma Carboplatin AUC = 6 IV day 1 every 21-days for up to 4 cycles Paclitaxel 200 mg/m2 IV day 1 every 21-days for up to 4 cycles OR For Non-squamous Carcinoma\> Carboplatin AUC = 6 IV day 1 every 21-days for up to 4 cycles Pemetrexed 500 mg/m2 IV day 1 every 21-days for up to 4 cycles Carboplatin: Dose frequency of Q3W, Day 1 of each cycle (standard Chemotherapy) Paclitaxel: Dose frequency of Q3W, Day 1 of each cycle (standard Chemotherapy) Pemetrexed: Dose frequency of Q3W, Day 1 of each cycle (standard Chemotherapy)	Arm B (Both Squamous and Non-Squamous) n=47 Participants MK-3475 200 mg/m2 IV every 21-days for up to 4 cycles\> \>\> \> \>\> Patients with CR, PR, or SD by irRC will then be treated with:\> \>\> \> \>\> For Squamous Carcinoma:\> \>\> \> \>\> Carboplatin AUC = 6 IV day 1 every 21-days for up to 4 cycles\> \>\> Paclitaxel 200 mg/m2 IV day 1 every 21-days for up to 4 cycles\> \>\> \> \>\> OR\> \>\> \> \>\> For Non-squamous Carcinoma\> \>\> \> \>\> Carboplatin AUC = 6 IV day 1 every 21-days for up to 4 cycles\> \>\> Pemetrexed 500 mg/m2 IV day 1 every 21-days for up to 4 cycles\> \>\> \> \>\> MK-3475: Dose frequency of Q3W, Day 1 of each cycle\> \>\> \> \>\> Carboplatin: Dose frequency of Q3W, Day 1 of each cycle (standard Chemotherapy)\> \>\> \> \>\> Paclitaxel: Dose frequency of Q3W, Day 1 of each cycle (standard Chemotherapy)\> \>\> \> \>\> Pemetrexed: Dose frequency of Q3W, Day 1 of each cycle (standard Chemotherapy)	Arm B Squamous Carcinoma Pemetrexed: Dose frequency of Q3W, Day 1 of each cycle (standard Chemotherapy)	Arm B Non-squamous Carcinoma Pemetrexed: Dose frequency of Q3W, Day 1 of each cycle (standard Chemotherapy)
Compare Progression-Free Survival (PFS) Per RECIST 1.1	5.8 Months Interval 4.4 to 10.6	4.0 Months Interval 2.1 to 10.3	—	—

SECONDARY outcome

Timeframe: 24 Months

To characterize the adverse events related to MK-3475 by frequency, type and grade in patients with Chemotherapy naive advanced NSCLC based on the sequence of administration with first-line chemotherapy. A count of participants experiencing an adverse event is summarized here, the detailed summary is in the adverse events section of this report.

Outcome measures

Outcome measures
Measure	Arm A (Both Squamous and Non-Squamous) n=9 Participants For Squamous Carcinoma Carboplatin AUC = 6 IV day 1 every 21-days for up to 4 cycles Paclitaxel 200 mg/m2 IV day 1 every 21-days for up to 4 cycles OR For Non-squamous Carcinoma\> Carboplatin AUC = 6 IV day 1 every 21-days for up to 4 cycles Pemetrexed 500 mg/m2 IV day 1 every 21-days for up to 4 cycles Carboplatin: Dose frequency of Q3W, Day 1 of each cycle (standard Chemotherapy) Paclitaxel: Dose frequency of Q3W, Day 1 of each cycle (standard Chemotherapy) Pemetrexed: Dose frequency of Q3W, Day 1 of each cycle (standard Chemotherapy)	Arm B (Both Squamous and Non-Squamous) n=34 Participants MK-3475 200 mg/m2 IV every 21-days for up to 4 cycles\> \>\> \> \>\> Patients with CR, PR, or SD by irRC will then be treated with:\> \>\> \> \>\> For Squamous Carcinoma:\> \>\> \> \>\> Carboplatin AUC = 6 IV day 1 every 21-days for up to 4 cycles\> \>\> Paclitaxel 200 mg/m2 IV day 1 every 21-days for up to 4 cycles\> \>\> \> \>\> OR\> \>\> \> \>\> For Non-squamous Carcinoma\> \>\> \> \>\> Carboplatin AUC = 6 IV day 1 every 21-days for up to 4 cycles\> \>\> Pemetrexed 500 mg/m2 IV day 1 every 21-days for up to 4 cycles\> \>\> \> \>\> MK-3475: Dose frequency of Q3W, Day 1 of each cycle\> \>\> \> \>\> Carboplatin: Dose frequency of Q3W, Day 1 of each cycle (standard Chemotherapy)\> \>\> \> \>\> Paclitaxel: Dose frequency of Q3W, Day 1 of each cycle (standard Chemotherapy)\> \>\> \> \>\> Pemetrexed: Dose frequency of Q3W, Day 1 of each cycle (standard Chemotherapy)	Arm B Squamous Carcinoma n=10 Participants Pemetrexed: Dose frequency of Q3W, Day 1 of each cycle (standard Chemotherapy)	Arm B Non-squamous Carcinoma n=37 Participants Pemetrexed: Dose frequency of Q3W, Day 1 of each cycle (standard Chemotherapy)
Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability)	9 participants	34 participants	10 participants	37 participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 24 Months

Other events: 46 other events

Deaths: 10 deaths

"Carboplatin + Paclitaxel"

Serious events: 4 serious events

Other events: 12 other events

Deaths: 5 deaths

Serious adverse events

Other adverse events

Additional Information

Thomas Hensing

NorthShore Medical Group

Phone: 847.570.2112

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	MK-3475 n=67 participants at risk MK-3475 200 mg Q3W	Carboplatin + Pemetrexed n=47 participants at risk For Non-squamous Carcinoma Carboplatin AUC = 6 IV day 1 every 21-days for up to 4 cycles Pemetrexed 500 mg/m2 IV day 1 every 21-days for up to 4 cycles Carboplatin: Dose frequency of Q3W, Day 1 of each cycle (standard Chemotherapy) Paclitaxel: Dose frequency of Q3W, Day 1 of each cycle (standard Chemotherapy) Pemetrexed: Dose frequency of Q3W, Day 1 of each cycle (standard Chemotherapy)	"Carboplatin + Paclitaxel" n=13 participants at risk Carcinoma Carboplatin AUC = 6 IV day 1 every 21-days for up to 4 cycles Pemetrexed 500 mg/m2 IV day 1 every 21-days for up to 4 cycles MK-3475: Dose frequency of Q3W, Day 1 of each cycle Carboplatin: Dose frequency of Q3W, Day 1 of each cycle (standard Chemotherapy) Paclitaxel: Dose frequency of Q3W, Day 1 of each cycle (standard Chemotherapy) Pemetrexed: Dose frequency of Q3W, Day 1 of each cycle (standard Chemotherapy)
Blood and lymphatic system disorders Blood and lymph sys disorders - Oth Spec	0.00% 0/67 • 24 months The descriptions and grading scales found in the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4 will be utilized for AE reporting.	2.1% 1/47 • Number of events 1 • 24 months The descriptions and grading scales found in the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4 will be utilized for AE reporting.	0.00% 0/13 • 24 months The descriptions and grading scales found in the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4 will be utilized for AE reporting.
Blood and lymphatic system disorders Febrile neutropenia	0.00% 0/67 • 24 months The descriptions and grading scales found in the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4 will be utilized for AE reporting.	0.00% 0/47 • 24 months The descriptions and grading scales found in the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4 will be utilized for AE reporting.	7.7% 1/13 • Number of events 1 • 24 months The descriptions and grading scales found in the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4 will be utilized for AE reporting.
Cardiac disorders Atrial fibrillation	0.00% 0/67 • 24 months The descriptions and grading scales found in the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4 will be utilized for AE reporting.	2.1% 1/47 • Number of events 1 • 24 months The descriptions and grading scales found in the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4 will be utilized for AE reporting.	0.00% 0/13 • 24 months The descriptions and grading scales found in the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4 will be utilized for AE reporting.
Cardiac disorders Atrial flutter	1.5% 1/67 • Number of events 1 • 24 months The descriptions and grading scales found in the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4 will be utilized for AE reporting.	0.00% 0/47 • 24 months The descriptions and grading scales found in the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4 will be utilized for AE reporting.	0.00% 0/13 • 24 months The descriptions and grading scales found in the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4 will be utilized for AE reporting.
Cardiac disorders Heart failure	1.5% 1/67 • Number of events 1 • 24 months The descriptions and grading scales found in the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4 will be utilized for AE reporting.	0.00% 0/47 • 24 months The descriptions and grading scales found in the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4 will be utilized for AE reporting.	0.00% 0/13 • 24 months The descriptions and grading scales found in the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4 will be utilized for AE reporting.
Cardiac disorders Myocardial infarction	1.5% 1/67 • Number of events 1 • 24 months The descriptions and grading scales found in the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4 will be utilized for AE reporting.	0.00% 0/47 • 24 months The descriptions and grading scales found in the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4 will be utilized for AE reporting.	0.00% 0/13 • 24 months The descriptions and grading scales found in the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4 will be utilized for AE reporting.
Cardiac disorders Sinus tachycardia	1.5% 1/67 • Number of events 1 • 24 months The descriptions and grading scales found in the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4 will be utilized for AE reporting.	0.00% 0/47 • 24 months The descriptions and grading scales found in the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4 will be utilized for AE reporting.	7.7% 1/13 • Number of events 1 • 24 months The descriptions and grading scales found in the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4 will be utilized for AE reporting.
Gastrointestinal disorders Abdominal pain	1.5% 1/67 • Number of events 3 • 24 months The descriptions and grading scales found in the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4 will be utilized for AE reporting.	0.00% 0/47 • 24 months The descriptions and grading scales found in the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4 will be utilized for AE reporting.	0.00% 0/13 • 24 months The descriptions and grading scales found in the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4 will be utilized for AE reporting.
Gastrointestinal disorders Colitis	0.00% 0/67 • 24 months The descriptions and grading scales found in the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4 will be utilized for AE reporting.	2.1% 1/47 • Number of events 2 • 24 months The descriptions and grading scales found in the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4 will be utilized for AE reporting.	0.00% 0/13 • 24 months The descriptions and grading scales found in the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4 will be utilized for AE reporting.
Gastrointestinal disorders Nausea	1.5% 1/67 • Number of events 1 • 24 months The descriptions and grading scales found in the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4 will be utilized for AE reporting.	0.00% 0/47 • 24 months The descriptions and grading scales found in the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4 will be utilized for AE reporting.	0.00% 0/13 • 24 months The descriptions and grading scales found in the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4 will be utilized for AE reporting.
Gastrointestinal disorders Vomiting	1.5% 1/67 • Number of events 2 • 24 months The descriptions and grading scales found in the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4 will be utilized for AE reporting.	0.00% 0/47 • 24 months The descriptions and grading scales found in the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4 will be utilized for AE reporting.	7.7% 1/13 • Number of events 1 • 24 months The descriptions and grading scales found in the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4 will be utilized for AE reporting.
General disorders Non-cardiac chest pain	1.5% 1/67 • Number of events 1 • 24 months The descriptions and grading scales found in the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4 will be utilized for AE reporting.	0.00% 0/47 • 24 months The descriptions and grading scales found in the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4 will be utilized for AE reporting.	0.00% 0/13 • 24 months The descriptions and grading scales found in the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4 will be utilized for AE reporting.
Infections and infestations Lung infection	1.5% 1/67 • Number of events 1 • 24 months The descriptions and grading scales found in the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4 will be utilized for AE reporting.	0.00% 0/47 • 24 months The descriptions and grading scales found in the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4 will be utilized for AE reporting.	7.7% 1/13 • Number of events 1 • 24 months The descriptions and grading scales found in the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4 will be utilized for AE reporting.
Infections and infestations Sepsis	1.5% 1/67 • Number of events 1 • 24 months The descriptions and grading scales found in the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4 will be utilized for AE reporting.	0.00% 0/47 • 24 months The descriptions and grading scales found in the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4 will be utilized for AE reporting.	0.00% 0/13 • 24 months The descriptions and grading scales found in the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4 will be utilized for AE reporting.
Infections and infestations Soft tissue infection	1.5% 1/67 • Number of events 1 • 24 months The descriptions and grading scales found in the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4 will be utilized for AE reporting.	0.00% 0/47 • 24 months The descriptions and grading scales found in the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4 will be utilized for AE reporting.	0.00% 0/13 • 24 months The descriptions and grading scales found in the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4 will be utilized for AE reporting.
Injury, poisoning and procedural complications Fracture	0.00% 0/67 • 24 months The descriptions and grading scales found in the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4 will be utilized for AE reporting.	2.1% 1/47 • Number of events 1 • 24 months The descriptions and grading scales found in the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4 will be utilized for AE reporting.	0.00% 0/13 • 24 months The descriptions and grading scales found in the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4 will be utilized for AE reporting.
Injury, poisoning and procedural complications Hip fracture	1.5% 1/67 • Number of events 1 • 24 months The descriptions and grading scales found in the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4 will be utilized for AE reporting.	0.00% 0/47 • 24 months The descriptions and grading scales found in the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4 will be utilized for AE reporting.	0.00% 0/13 • 24 months The descriptions and grading scales found in the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4 will be utilized for AE reporting.
Injury, poisoning and procedural complications Spinal fracture	1.5% 1/67 • Number of events 1 • 24 months The descriptions and grading scales found in the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4 will be utilized for AE reporting.	0.00% 0/47 • 24 months The descriptions and grading scales found in the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4 will be utilized for AE reporting.	0.00% 0/13 • 24 months The descriptions and grading scales found in the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4 will be utilized for AE reporting.
Investigations Neutrophil count decreased	1.5% 1/67 • Number of events 1 • 24 months The descriptions and grading scales found in the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4 will be utilized for AE reporting.	2.1% 1/47 • Number of events 1 • 24 months The descriptions and grading scales found in the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4 will be utilized for AE reporting.	0.00% 0/13 • 24 months The descriptions and grading scales found in the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4 will be utilized for AE reporting.
Investigations Platelet count decreased	1.5% 1/67 • Number of events 1 • 24 months The descriptions and grading scales found in the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4 will be utilized for AE reporting.	0.00% 0/47 • 24 months The descriptions and grading scales found in the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4 will be utilized for AE reporting.	0.00% 0/13 • 24 months The descriptions and grading scales found in the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4 will be utilized for AE reporting.
Musculoskeletal and connective tissue disorders Musculoskeletal, conn tissue - Oth spec	1.5% 1/67 • Number of events 1 • 24 months The descriptions and grading scales found in the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4 will be utilized for AE reporting.	2.1% 1/47 • Number of events 1 • 24 months The descriptions and grading scales found in the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4 will be utilized for AE reporting.	0.00% 0/13 • 24 months The descriptions and grading scales found in the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4 will be utilized for AE reporting.
Nervous system disorders Nervous system disorders - Oth spec	1.5% 1/67 • Number of events 1 • 24 months The descriptions and grading scales found in the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4 will be utilized for AE reporting.	0.00% 0/47 • 24 months The descriptions and grading scales found in the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4 will be utilized for AE reporting.	0.00% 0/13 • 24 months The descriptions and grading scales found in the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4 will be utilized for AE reporting.
Nervous system disorders Seizure	1.5% 1/67 • Number of events 1 • 24 months The descriptions and grading scales found in the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4 will be utilized for AE reporting.	0.00% 0/47 • 24 months The descriptions and grading scales found in the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4 will be utilized for AE reporting.	0.00% 0/13 • 24 months The descriptions and grading scales found in the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4 will be utilized for AE reporting.
Nervous system disorders Syncope	3.0% 2/67 • Number of events 2 • 24 months The descriptions and grading scales found in the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4 will be utilized for AE reporting.	0.00% 0/47 • 24 months The descriptions and grading scales found in the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4 will be utilized for AE reporting.	7.7% 1/13 • Number of events 1 • 24 months The descriptions and grading scales found in the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4 will be utilized for AE reporting.
Respiratory, thoracic and mediastinal disorders Adult respiratory distress syndrome	1.5% 1/67 • Number of events 1 • 24 months The descriptions and grading scales found in the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4 will be utilized for AE reporting.	0.00% 0/47 • 24 months The descriptions and grading scales found in the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4 will be utilized for AE reporting.	0.00% 0/13 • 24 months The descriptions and grading scales found in the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4 will be utilized for AE reporting.
Respiratory, thoracic and mediastinal disorders Dyspnea	1.5% 1/67 • Number of events 1 • 24 months The descriptions and grading scales found in the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4 will be utilized for AE reporting.	2.1% 1/47 • Number of events 1 • 24 months The descriptions and grading scales found in the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4 will be utilized for AE reporting.	0.00% 0/13 • 24 months The descriptions and grading scales found in the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4 will be utilized for AE reporting.
Respiratory, thoracic and mediastinal disorders Resp, thoracic, mediastinal - Oth spec	1.5% 1/67 • Number of events 1 • 24 months The descriptions and grading scales found in the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4 will be utilized for AE reporting.	0.00% 0/47 • 24 months The descriptions and grading scales found in the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4 will be utilized for AE reporting.	7.7% 1/13 • Number of events 1 • 24 months The descriptions and grading scales found in the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4 will be utilized for AE reporting.
Vascular disorders Thromboembolic event	4.5% 3/67 • Number of events 3 • 24 months The descriptions and grading scales found in the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4 will be utilized for AE reporting.	0.00% 0/47 • 24 months The descriptions and grading scales found in the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4 will be utilized for AE reporting.	0.00% 0/13 • 24 months The descriptions and grading scales found in the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4 will be utilized for AE reporting.