PROTECT2: Phase III Study Comparing the Efficacy and Safety of LA-EP2006 and Peg-Filgrastim

• Sponsor: Sandoz (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01516736
• Collaborator: Sandoz GmbH (Industry)
• Enrollment: 308
• Locations: 53
• Arms: 2
• Duration (Months): 21
• Patients Per Site: 5.8
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

The study will assess the efficacy of LA-EP2006 compared to Neulasta® with respect to the mean duration of severe neutropenia during treatment with myelosuppressive chemotherapy in breast cancer patients.

Condition or Disease	Intervention/Treatment	Phase
Chemotherapy-induced Neutropenia; Breast Cancer	Drug: LA-EP2006; Drug: Neulasta®	Phase 3

Detailed Description

The Pegfilgrastim Randomized Oncology (Supportive Care) Trial to Evaluate Comparative Treatment (PROTECT-2) was a confirmatory efficacy and safety study designed to compare the proposed biosimilar LA-EP2006 with the reference pegfilgrastim in woman with early stage breast cancer receiving (neo)-adjuvant myelosuppressive chemotherapy. Patient received TAC (intravenous docetaxel 75mg/m^{2, doxorubicin 50 mg/m}2, and cyclophosphamide 500mg/m^{2) on day1 of each cycle, for six or more cycles. A total of 308 patients were randomized to LA-EP2006 (n=155) or reference Neulasta® (n=153). Treatment was given subcutaneously on day 2 of each cycle. The primary end point was the duration of severe neutropenia (DSN) during Cycle 1 (defined as number of consecutive days with absolute neutrophil count <0.5 × 10}9 cells/L). LA-EP2006 was equivalent to the reference product in DSN (difference: -0.16 days; 95% CI [-0.40, 0.08]). Further, LA-EP2006 and the reference pegfilgrastim showed no clinically meaningful differences regarding efficacy and safety.

Study Design

• Study Type: Interventional
• Actual Enrollment: 308 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Supportive Care
• Official Title: Pivotal Study in Breast Cancer Patients Investigating Efficacy and Safety of LA-EP2006 and Neulasta®
• Study Start Date: Mar 1, 2012
• Actual Primary Completion Date: Aug 1, 2013
• Actual Study Completion Date: Dec 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: LA-EP2006 During each chemotherapy cycle eligible patients receive LA-EP2006 s.c. post chemotherapy application.	Drug: LA-EP2006; Eligible patients are scheduled to receive six cycles of chemotherapy every three weeks. During each chemotherapy cycle LA-EP2006 is injected s.c. post chemotherapy application.; Other Names: pegfilgrastim
Active Comparator: Neulasta® During each chemotherapy cycle eligible patients receive Neulasta® s.c. post chemotherapy application.	Drug: Neulasta®; Eligible patients are scheduled to receive six cycles of chemotherapy every three weeks. During each chemotherapy cycle Neulasta® is injected s.c. post chemotherapy application.; Other Names: pegfilgrastim Neulasta

Outcome Measures

Primary Outcome Measures

1. Mean Duration of Severe Neutropenia (DSN) During Cycle 1 of Chemotherapy [21 days (Cycle 1 of chemotherapy treatment)]

   Mean duration of severe neutropenia, defined as number of consecutive days with ANC <0.5 × 10^9/l (grade 4 neutropenia).

Secondary Outcome Measures

1. Incidence of Febrile Neutropenia (FN) [across all cycles (18 weeks)]

   FN was defined as oral temperature ≥ 38.3°C while having an absolute neutrophil count (ANC) < 0.5 × 10^9 cells/L. Serious treatment-emergent adverse events (TEAEs) were reconciled with the fever and ANC results recorded in the patient diary and CRF and therefore only the serious TEAEs of FN ("febrile neutropenia", "neutropenic sepsis") were taken into account.

2. Number of Patients With at Least One Episode of Fever by Cycle and Across All Cycles [across al cycles (18 weeks)]

   Fever was defined as an oral body temperature of ≥ 38.3°C. Fever episodes were described by maximum oral temperature and the number of patients who had fever at least once.

3. Depth of ANC Nadir in Cycle 1 [Cycle 1 (3 weeks)]

   The depth of ANC nadir was defined as the patient's lowest ANC (10^9 cells/L) in Cycle 1.

4. Number of Patients With ANC Nadir Per Day in Cycle 1 [Cycle 1 (3 weeks)]

   Numbers of patients with ANC nadir based per day during Cycle 1 are given.

5. Time to ANC Recovery in Days in Cycle 1 [across Cycle 1 (3 weeks)]

   Time to absolute neutrophil count (ANC) recovery was defined as the time in days from ANC nadir until the patient's ANC had increased to ≥ 2 × 10^9 cells/L after the nadir in Cycle 1.

6. Frequency of Infections by Cycle and Across All Cycles [across all cycles (18 weeks)]

   The number of patients with infections was recorded for each cycle and across all cycles. Infections were identified by the AE documentation page selecting all events coded with System Organ Class "Infections and Infestations".

7. Mortality Due to Infection [Study course (19 weeks)]

   Number of patients with death due to infections

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• histologically proven breast cancer

• eligible for six cycles of neoadjuvant or adjuvant chemotherapy

Exclusion Criteria:

• concurrent or prior chemotherapy for breast cancer

• concurrent or prior anti-cancer treatment for breast cancer such as endocrine therapy, immunotherapy, monoclonal antibodies, and/or biological therapy

• concurrent prophylactic antibiotics

• previous therapy with any G-CSF (granulocyte-colony stimulating factor) product

Other protocol-defined inclusion/exclusion criteria may apply.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Sandoz Investigational Site	Hot Springs	Arkansas	United States	71913
2	Sandoz Investigational Site	Jonesboro	Arkansas	United States	72401
3	Sandoz Investigational Site	Corona	California	United States	92879
4	Sandoz Investigational Site	Wichita	Kansas	United States	67214
5	Sandoz Investigational Site	Mount Sterling	Kentucky	United States	40353
6	Sandoz Investigational Site	Detroit	Michigan	United States	48202
7	Sandoz Investigational Site	Bismarck	North Dakota	United States	58501
8	Sandoz Investigational Site	Eugene	Oregon	United States	97401
9	Sandoz Investigational Site	Germantown	Tennessee	United States	38138
10	Sandoz Investigational Site	Newport News	Virginia	United States	23601
11	Sandoz Investigational Site	Tucuman		Argentina	4000
12	Sandoz Investigational Site	Temuco		Chile	4810469
13	Sandoz Investigational Site	Chennai		India	600031
14	Sandoz Investigational Site	Delhi		India	110092
15	Sandoz Investigational Site	Gujarat		India	380009
16	Sandoz Investigational Site	Hyderabad		India	50024
17	Sandoz Investigational Site	Karamsad		India	388325
18	Sandoz Investigational Site	Lucknow		India	226003
19	Sandoz Investigational Site	Maharashtra		India	422004
20	Sandoz Investigational Site	Mangalore		India	575001
21	Sandoz Investigational Site	Mumbai		India	400010
22	Sandoz Investigational Site	Pradesh		India	520002
23	Sandoz Investigational Site	Surat		India	395010
24	Sandoz Investigational Site	Vadodara		India	391760
25	Sandoz Investigational Site	Vellore		India	632004
26	Sandoz Investigational Site	Visakhapatnam		India	530017
27	Sandoz Investigational Site	Kelantan		Malaysia	16150
28	Sandoz Investigational Site	Nilai		Malaysia	71800
29	Sandoz Investigational Site	Penang		Malaysia	11200
30	Sandoz Investigational Site	Penang		Malaysia	11600
31	Sandoz Investigational Site	San Juan		Puerto Rico	00910
32	Sandoz Investigational Site	San Juan		Puerto Rico	00927
33	Sandoz Investigational Site	Arkhangelsk		Russian Federation	163045
34	Sandoz Investigational Site	Bashkortostan		Russian Federation	450054
35	Sandoz Investigational Site	Bryansk		Russian Federation	241033
36	Sandoz Investigational Site	Kazan		Russian Federation	420029
37	Sandoz Investigational Site	Krasnoyarsk		Russian Federation	660133
38	Sandoz Investigational Site	Moscow		Russian Federation	115478
39	Sandoz Investigational Site	Omsk		Russian Federation	644046
40	Sandoz Investigational Site	Orel		Russian Federation	302020
41	Sandoz Investigational Site	Orenburg		Russian Federation	460021
42	Sandoz Investigational Site	Rostov-na-Donu		Russian Federation	344037
43	Sandoz Investigational Site	St Petersburg		Russian Federation	197758
44	Sandoz Investigational Site	St. Petersburg		Russian Federation	194017
45	Sandoz Investigational Site	St. Petersburg		Russian Federation	194044
46	Sandoz Investigational Site	St. Petersburg		Russian Federation	195271
47	Sandoz Investigational Site	St. Petersburg		Russian Federation	197022
48	Sandoz Investigational Site	Tomsk		Russian Federation	634009
49	Sandoz Investigational Site	Vladimir		Russian Federation	600021
50	Sandoz Investigational Site	Barcelona		Spain	08035
51	Sandoz Investigational Site	Madrid		Spain	28040
52	Sandoz Investigational Site	Santiago de Compostela		Spain	15706
53	Sandoz Investigational Site	Valencia		Spain	46014

Sponsors and Collaborators

• Sandoz
• Sandoz GmbH

Investigators

• Study Chair: Sandoz Biopharmaceutical Clinical Development, Sandoz Biopharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Publications

• Blackwell K, Donskih R, Jones CM, Nixon A, Vidal MJ, Nakov R, Singh P, Schaffar G, Gascón P, Harbeck N. A Comparison of Proposed Biosimilar LA-EP2006 and Reference Pegfilgrastim for the Prevention of Neutropenia in Patients With Early-Stage Breast Cancer Receiving Myelosuppressive Adjuvant or Neoadjuvant Chemotherapy: Pegfilgrastim Randomized Oncology (Supportive Care) Trial to Evaluate Comparative Treatment (PROTECT-2), a Phase III, Randomized, Double-Blind Trial. Oncologist. 2016 Jul;21(7):789-94. doi: 10.1634/theoncologist.2016-0011. Epub 2016 Apr 18.

• Responsible Party: Sandoz
• ClinicalTrials.gov Identifier: NCT01516736
• Other Study ID Numbers: LA-EP06-302
• First Posted: Jan 25, 2012
• Last Update Posted: Aug 30, 2017
• Last Verified: Aug 1, 2017

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Keywords provided by Sandoz: Pegfilgrastim; G-CSF; neutropenia; breast cancer; myelosuppressive chemotherapy
• Additional relevant MeSH terms: Breast Neoplasms; Neutropenia

Study Results

Participant Flow

Arm/Group Title	LA-EP2006	Neulasta®
Arm/Group Description	During each chemotherapy cycle eligible patients receive LA-EP2006 s.c. post chemotherapy application. LA-EP2006: Eligible patients are scheduled to receive six cycles of chemotherapy every three weeks. During each chemotherapy cycle LA-EP2006 is injected s.c. post chemotherapy application.	During each chemotherapy cycle eligible patients receive Neulasta® s.c. post chemotherapy application. Neulasta®: Eligible patients are scheduled to receive six cycles of chemotherapy every three weeks. During each chemotherapy cycle pegfilgrastim is injected s.c. post chemotherapy application.
Period Title: Overall Study
STARTED	155	153
COMPLETED	135	140
NOT COMPLETED	20	13

Baseline Characteristics

Arm/Group Title	LA-EP2006	Neulasta®	Total
Arm/Group Description	During each chemotherapy cycle eligible patients receive LA-EP2006 s.c. post chemotherapy application. LA-EP2006: Eligible patients are scheduled to receive six cycles of chemotherapy every three weeks. During each chemotherapy cycle LA-EP2006 is injected s.c. post chemotherapy application.	During each chemotherapy cycle eligible patients receive Neulasta® s.c. post chemotherapy application. Neulasta®: Eligible patients are scheduled to receive six cycles of chemotherapy every three weeks. During each chemotherapy cycle pegfilgrastim is injected s.c. post chemotherapy application.	Total of all reporting groups
Overall Participants	155	153	308
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	48.8 (10.50)	49.1 (10.07)	48.9 (10.27)
Sex: Female, Male (Count of Participants)
Female	155 100%	153 100%	308 100%
Male	0 0%	0 0%	0 0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	10 6.5%	6 3.9%	16 5.2%
Not Hispanic or Latino	145 93.5%	147 96.1%	292 94.8%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	62 40%	58 37.9%	120 39%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	1 0.6%	2 1.3%	3 1%
White	90 58.1%	93 60.8%	183 59.4%
More than one race	2 1.3%	0 0%	2 0.6%
Unknown or Not Reported	0 0%	0 0%	0 0%
BMI (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	26.56 (5.771)	26.49 (5.126)	26.53 (5.450)
Time since diagnosis (months) [Median (Full Range) ]
Median (Full Range) [months]	1.28	1.28	1.28
Disease stage (Count of Participants)
I	7 4.5%	13 8.5%	20 6.5%
II	70 45.2%	61 39.9%	131 42.5%
III	78 50.3%	78 51%	156 50.6%
IV	0 0%	1 0.7%	1 0.3%
Previous breast cancer surgery (Count of Participants)
Count of Participants [Participants]	154 99.4%	152 99.3%	306 99.4%
Previous radiotherapy (Count of Participants)
Count of Participants [Participants]	2 1.3%	1 0.7%	3 1%
ECOG performance status (Count of Participants)
0	117 75.5%	110 71.9%	227 73.7%
1	36 23.2%	43 28.1%	79 25.6%
2	2 1.3%	0 0%	2 0.6%

Outcome Measures

1. Primary Outcome

Title	Mean Duration of Severe Neutropenia (DSN) During Cycle 1 of Chemotherapy
Description	Mean duration of severe neutropenia, defined as number of consecutive days with ANC <0.5 × 10^9/l (grade 4 neutropenia).
Time Frame	21 days (Cycle 1 of chemotherapy treatment)

Outcome Measure Data

Analysis Population Description

Missing patients in FAS set due to blind data review meeting decision (no ANC profiles available). FAS set = full analysis set; PP set = per protocol set

Arm/Group Title	LA-EP2006	Neulasta®
Arm/Group Description	During each chemotherapy cycle eligible patients receive LA-EP2006 s.c. post chemotherapy application. LA-EP2006: Eligible patients are scheduled to receive six cycles of chemotherapy every three weeks. During each chemotherapy cycle LA-EP2006 is injected s.c. post chemotherapy application.	During each chemotherapy cycle eligible patients receive Neulasta® s.c. post chemotherapy application. Neulasta®: Eligible patients are scheduled to receive six cycles of chemotherapy every three weeks. During each chemotherapy cycle pegfilgrastim is injected s.c. post chemotherapy application.
Measure Participants	155	153
FAS	1.36 (1.133)	1.19 (0.984)
PP	1.34 (1.141)	1.19 (0.991)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	LA-EP2006, Neulasta®
	Comments	The primary objective of the study was to compare LA-EP2006 and Neulasta in terms of the DSN in Cycle 1. It was to be shown in a hierarchical way: that LA-EP2006 is equivalent (margin: ±1 day) to Neulasta® with respect to DSN duration in Cycle 1 and, if this was successfully established, that LA-EP2006 is non-inferior (margin: -0.6 days) to Neulasta® with respect to DSN duration in Cycle 1.
	Type of Statistical Test	Equivalence
	Comments	The testing procedure was set up in a hierarchical structure, where first equivalence between LA-EP2006 and Neulasta® was assessed (margin ±1 day) and only if this was successfully established, non-inferiority between the two products was tested using a tighter margin of -0.6 days.
Statistical Test of Hypothesis	p-Value	0.05
	Comments
	Method	ANCOVA
	Comments	The primary endpoints was analyzed with analysis of covariance (ANCOVA).
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.16
	Confidence Interval	(2-Sided) 95%; -0.40 to 0.08
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	LA-EP2006, Neulasta®
	Comments	The primary objective of the study was to compare LA-EP2006 and Neulasta in terms of the DSN in Cycle 1. It was to be shown in a hierarchical way: that LA-EP2006 is equivalent (margin: ±1 day) to Neulasta® with respect to DSN duration in Cycle 1 and, if this was successfully established, that LA-EP2006 is non-inferior (margin: -0.6 days) to Neulasta® with respect to DSN duration in Cycle 1.
	Type of Statistical Test	Non-Inferiority
	Comments	The testing procedure was set up in a hierarchical structure, where first equivalence between LA-EP2006 and Neulasta® was assessed (margin ±1 day) and only if this was successfully established, non-inferiority between the two products was tested using a tighter margin of -0.6 days.
Statistical Test of Hypothesis	p-Value	0.05
	Comments
	Method	ANCOVA
	Comments	The primary endpoints was analyzed with analysis of covariance (ANCOVA).
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.16
	Confidence Interval	(2-Sided) 95%; -0.40 to 0.08
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Incidence of Febrile Neutropenia (FN)
Description	FN was defined as oral temperature ≥ 38.3°C while having an absolute neutrophil count (ANC) < 0.5 × 10^9 cells/L. Serious treatment-emergent adverse events (TEAEs) were reconciled with the fever and ANC results recorded in the patient diary and CRF and therefore only the serious TEAEs of FN ("febrile neutropenia", "neutropenic sepsis") were taken into account.
Time Frame	across all cycles (18 weeks)

Outcome Measure Data

Analysis Population Description

FAS set = full analysis set

Arm/Group Title	LA-EP2006	Neulasta®
Arm/Group Description	During each chemotherapy cycle eligible patients receive LA-EP2006 s.c. post chemotherapy application. LA-EP2006: Eligible patients are scheduled to receive six cycles of chemotherapy every three weeks. During each chemotherapy cycle LA-EP2006 is injected s.c. post chemotherapy application.	During each chemotherapy cycle eligible patients receive Neulasta® s.c. post chemotherapy application. Neulasta®: Eligible patients are scheduled to receive six cycles of chemotherapy every three weeks. During each chemotherapy cycle pegfilgrastim is injected s.c. post chemotherapy application.
Measure Participants	155	153
Cycle 1	12 7.7%	15 9.8%
Cycle 2	0 0%	3 2%
Cycle 3	3 1.9%	1 0.7%
Cycle 4	2 1.3%	1 0.7%
Cycle 5	0 0%	1 0.7%
Cycle 6	2 1.3%	1 0.7%
All cycles (at least on incidence)	16 10.3%	20 13.1%

3. Secondary Outcome

Title	Number of Patients With at Least One Episode of Fever by Cycle and Across All Cycles
Description	Fever was defined as an oral body temperature of ≥ 38.3°C. Fever episodes were described by maximum oral temperature and the number of patients who had fever at least once.
Time Frame	across al cycles (18 weeks)

Outcome Measure Data

Analysis Population Description

Patients with more than 1 event during the study (overall) are counted only once. FAS set = full analysis set

Arm/Group Title	LA-EP2006	Neulasta®
Arm/Group Description	During each chemotherapy cycle eligible patients receive LA-EP2006 s.c. post chemotherapy application. LA-EP2006: Eligible patients are scheduled to receive six cycles of chemotherapy every three weeks. During each chemotherapy cycle LA-EP2006 is injected s.c. post chemotherapy application.	During each chemotherapy cycle eligible patients receive Neulasta® s.c. post chemotherapy application. Neulasta®: Eligible patients are scheduled to receive six cycles of chemotherapy every three weeks. During each chemotherapy cycle pegfilgrastim is injected s.c. post chemotherapy application.
Measure Participants	155	153
Cycle 1	13 8.4%	17 11.1%
Cycle 2	8 5.2%	6 3.9%
Cycle 3	4 2.6%	7 4.6%
Cycle 4	5 3.2%	10 6.5%
Cycle 5	3 1.9%	3 2%
Cycle 6	5 3.2%	4 2.6%
Overall	32 20.6%	35 22.9%

4. Secondary Outcome

Title	Depth of ANC Nadir in Cycle 1
Description	The depth of ANC nadir was defined as the patient's lowest ANC (10^9 cells/L) in Cycle 1.
Time Frame	Cycle 1 (3 weeks)

Outcome Measure Data

Analysis Population Description

FAS set = full analysis set

Arm/Group Title	LA-EP2006	Neulasta®
Arm/Group Description	During each chemotherapy cycle eligible patients receive LA-EP2006 s.c. post chemotherapy application. LA-EP2006: Eligible patients are scheduled to receive six cycles of chemotherapy every three weeks. During each chemotherapy cycle LA-EP2006 is injected s.c. post chemotherapy application.	During each chemotherapy cycle eligible patients receive Neulasta® s.c. post chemotherapy application. Neulasta®: Eligible patients are scheduled to receive six cycles of chemotherapy every three weeks. During each chemotherapy cycle pegfilgrastim is injected s.c. post chemotherapy application.
Measure Participants	152	149
Mean (Standard Deviation) [10^9 cells/L]	0.490 (0.7205)	0.444 (0.5684)

5. Secondary Outcome

Title	Number of Patients With ANC Nadir Per Day in Cycle 1
Description	Numbers of patients with ANC nadir based per day during Cycle 1 are given.
Time Frame	Cycle 1 (3 weeks)

Outcome Measure Data

Analysis Population Description

FAS set = full analysis set

Arm/Group Title	LA-EP2006	Neulasta®
Arm/Group Description	During each chemotherapy cycle eligible patients receive LA-EP2006 s.c. post chemotherapy application. LA-EP2006: Eligible patients are scheduled to receive six cycles of chemotherapy every three weeks. During each chemotherapy cycle LA-EP2006 is injected s.c. post chemotherapy application.	During each chemotherapy cycle eligible patients receive Neulasta® s.c. post chemotherapy application. Neulasta®: Eligible patients are scheduled to receive six cycles of chemotherapy every three weeks. During each chemotherapy cycle pegfilgrastim is injected s.c. post chemotherapy application.
Measure Participants	155	153
Days 1-5	1 0.6%	0 0%
Day 6	9 5.8%	8 5.2%
Day 7	117 75.5%	109 71.2%
Day 8	20 12.9%	30 19.6%
Day 9	3 1.9%	2 1.3%
Days 10-15	2 1.3%	0 0%
not definable	3 1.9%	4 2.6%

6. Secondary Outcome

Title	Time to ANC Recovery in Days in Cycle 1
Description	Time to absolute neutrophil count (ANC) recovery was defined as the time in days from ANC nadir until the patient's ANC had increased to ≥ 2 × 10^9 cells/L after the nadir in Cycle 1.
Time Frame	across Cycle 1 (3 weeks)

Outcome Measure Data

Analysis Population Description

FAS set = full analysis set

Arm/Group Title	LA-EP2006	Neulasta®
Arm/Group Description	During each chemotherapy cycle eligible patients receive LA-EP2006 s.c. post chemotherapy application. LA-EP2006: Eligible patients are scheduled to receive six cycles of chemotherapy every three weeks. During each chemotherapy cycle LA-EP2006 is injected s.c. post chemotherapy application.	During each chemotherapy cycle eligible patients receive Neulasta® s.c. post chemotherapy application. Neulasta®: Eligible patients are scheduled to receive six cycles of chemotherapy every three weeks. During each chemotherapy cycle pegfilgrastim is injected s.c. post chemotherapy application.
Measure Participants	155	153
Mean (Standard Deviation) [days]	2.11 (0.889)	2.04 (0.951)

7. Secondary Outcome

Title	Frequency of Infections by Cycle and Across All Cycles
Description	The number of patients with infections was recorded for each cycle and across all cycles. Infections were identified by the AE documentation page selecting all events coded with System Organ Class "Infections and Infestations".
Time Frame	across all cycles (18 weeks)

Outcome Measure Data

Analysis Population Description

Patients with more than 1 event during the study (overall) are counted only once. FAS set = full analysis set

Arm/Group Title	LA-EP2006	Neulasta®
Arm/Group Description	During each chemotherapy cycle eligible patients receive LA-EP2006 s.c. post chemotherapy application. LA-EP2006: Eligible patients are scheduled to receive six cycles of chemotherapy every three weeks. During each chemotherapy cycle LA-EP2006 is injected s.c. post chemotherapy application.	During each chemotherapy cycle eligible patients receive Neulasta® s.c. post chemotherapy application. Neulasta®: Eligible patients are scheduled to receive six cycles of chemotherapy every three weeks. During each chemotherapy cycle pegfilgrastim is injected s.c. post chemotherapy application.
Measure Participants	155	153
Cycle 1	10 6.5%	14 9.2%
Cycle 2	5 3.2%	3 2%
Cycle 3	2 1.3%	5 3.3%
Cycle 4	4 2.6%	5 3.3%
Cycle 5	2 1.3%	6 3.9%
Cycle 6	5 3.2%	5 3.3%
Overall	26 16.8%	32 20.9%

8. Secondary Outcome

Title	Mortality Due to Infection
Description	Number of patients with death due to infections
Time Frame	Study course (19 weeks)

Outcome Measure Data

Analysis Population Description

FAS set = full analysis set

Arm/Group Title	LA-EP2006	Neulasta®
Arm/Group Description	During each chemotherapy cycle eligible patients receive LA-EP2006 s.c. post chemotherapy application. LA-EP2006: Eligible patients are scheduled to receive six cycles of chemotherapy every three weeks. During each chemotherapy cycle LA-EP2006 is injected s.c. post chemotherapy application.	During each chemotherapy cycle eligible patients receive Neulasta® s.c. post chemotherapy application. Neulasta®: Eligible patients are scheduled to receive six cycles of chemotherapy every three weeks. During each chemotherapy cycle pegfilgrastim is injected s.c. post chemotherapy application.
Measure Participants	155	153
Yes	0 0%	0 0%
No	155 100%	153 100%

Adverse Events

Time Frame	Patients were followed for a 4-week safety period from the last administration of pegfilgrastim.
Adverse Event Reporting Description	Severity of treatment-emergent adverse events (TEAEs) was captured by CTCAE (Common Toxicology Criteria for Adverse Events) grading. SAF set = safety analysis set was used
Arm/Group Title	LA-EP2006		Neulasta®
Arm/Group Description	During each chemotherapy cycle eligible patients receive LA-EP2006 s.c. post chemotherapy application. LA-EP2006: Eligible patients are scheduled to receive six cycles of chemotherapy every three weeks. During each chemotherapy cycle LA-EP2006 is injected s.c. post chemotherapy application.		During each chemotherapy cycle eligible patients receive Neulasta® s.c. post chemotherapy application. Neulasta®: Eligible patients are scheduled to receive six cycles of chemotherapy every three weeks. During each chemotherapy cycle pegfilgrastim is injected s.c. post chemotherapy application.
All Cause Mortality
	LA-EP2006		Neulasta®
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/155 (1.9%)		2/153 (1.3%)
Serious Adverse Events
	LA-EP2006		Neulasta®
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	29/155 (18.7%)		32/153 (20.9%)
Blood and lymphatic system disorders
Febrile neutropenia	16/155 (10.3%)		19/153 (12.4%)
Neutropenia	4/155 (2.6%)		6/153 (3.9%)
Thrombocytopenia	1/155 (0.6%)		1/153 (0.7%)
Anemia	1/155 (0.6%)		0/153 (0%)
Cardiac disorders
Atrial fibrillation	0/155 (0%)		1/153 (0.7%)
Cardiac arrest	1/155 (0.6%)		0/153 (0%)
Cardio-respiratory arrest	1/155 (0.6%)		0/153 (0%)
Pericardial hemorrhage	1/155 (0.6%)		0/153 (0%)
Eye disorders
Eye irritation	0/155 (0%)		1/153 (0.7%)
Gastrointestinal disorders
Abdominal pain	3/155 (1.9%)		5/153 (3.3%)
Diarrhea	2/155 (1.3%)		5/153 (3.3%)
Vomiting	2/155 (1.3%)		4/153 (2.6%)
Abdominal discomfort	1/155 (0.6%)		0/153 (0%)
Constipation	0/155 (0%)		1/153 (0.7%)
Gastric ulcer hemorrhage	1/155 (0.6%)		0/153 (0%)
Gastritis	1/155 (0.6%)		0/153 (0%)
Nausea	0/155 (0%)		1/153 (0.7%)
Peptic ulcer	0/155 (0%)		1/153 (0.7%)
Proctalgia	0/155 (0%)		1/153 (0.7%)
Stomatitis	0/155 (0%)		1/153 (0.7%)
General disorders
Asthenia	0/155 (0%)		3/153 (2%)
Pyrexia	1/155 (0.6%)		2/153 (1.3%)
Non-cardiac chest pain	0/155 (0%)		1/153 (0.7%)
Hepatobiliary disorders
Hepatic hemorrhage	1/155 (0.6%)		0/153 (0%)
Hepatic necrosis	1/155 (0.6%)		0/153 (0%)
Infections and infestations
Gastroenteritis	0/155 (0%)		2/153 (1.3%)
Bronchitis	0/155 (0%)		1/153 (0.7%)
Clostridium difficile infection	1/155 (0.6%)		0/153 (0%)
Mastitis	0/155 (0%)		1/153 (0.7%)
Neutropenic sepsis	0/155 (0%)		1/153 (0.7%)
Staphylococcal infection	0/155 (0%)		1/153 (0.7%)
Upper respiratory tract infection	0/155 (0%)		1/153 (0.7%)
Investigations
Neutrophil count decreased	1/155 (0.6%)		0/153 (0%)
Platelet count decreased	1/155 (0.6%)		0/153 (0%)
White blood cell count decreased	1/155 (0.6%)		0/153 (0%)
Metabolism and nutrition disorders
Dehydration	2/155 (1.3%)		0/153 (0%)
Decreased appetite	1/155 (0.6%)		0/153 (0%)
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain	0/155 (0%)		2/153 (1.3%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer	0/155 (0%)		1/153 (0.7%)
Lung neoplasm	1/155 (0.6%)		0/153 (0%)
Nervous system disorders
Convulsion	1/155 (0.6%)		0/153 (0%)
Dizziness	1/155 (0.6%)		0/153 (0%)
Lethargy	1/155 (0.6%)		0/153 (0%)
Neuropathy peripheral	1/155 (0.6%)		0/153 (0%)
Psychiatric disorders
Completed suicide	0/155 (0%)		1/153 (0.7%)
Renal and urinary disorders
Renal failure	1/155 (0.6%)		0/153 (0%)
Renal hemorrhage	1/155 (0.6%)		0/153 (0%)
Reproductive system and breast disorders
Uterine hemorrhage	0/155 (0%)		1/153 (0.7%)
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism	2/155 (1.3%)		0/153 (0%)
Dyspnea	0/155 (0%)		1/153 (0.7%)
Organizing pneumonia	0/155 (0%)		1/153 (0.7%)
Pleural effusion	0/155 (0%)		1/153 (0.7%)
Vascular disorders
Hypotension	0/155 (0%)		1/153 (0.7%)
Shock hemorrhagic	1/155 (0.6%)		0/153 (0%)
Other (Not Including Serious) Adverse Events
	LA-EP2006		Neulasta®
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	147/155 (94.8%)		144/153 (94.1%)
Blood and lymphatic system disorders
Blood and lymphatic system disorders	77/155 (49.7%)		72/153 (47.1%)
Eye disorders
Eye disorders	8/155 (5.2%)		6/153 (3.9%)
Gastrointestinal disorders
Gastrointestinal disorders	111/155 (71.6%)		100/153 (65.4%)
General disorders
General disorders and administration site conditions	93/155 (60%)		90/153 (58.8%)
Infections and infestations
Infections and infestations	24/155 (15.5%)		27/153 (17.6%)
Injury, poisoning and procedural complications
Injury, poisoning and procedural complications	4/155 (2.6%)		5/153 (3.3%)
Investigations
Investigations	17/155 (11%)		14/153 (9.2%)
Metabolism and nutrition disorders
Metabolism and nutrition disorders	14/155 (9%)		21/153 (13.7%)
Musculoskeletal and connective tissue disorders
Musculoskeletal and connective tissue disorders	45/155 (29%)		40/153 (26.1%)
Nervous system disorders
Nervous system disorders	32/155 (20.6%)		25/153 (16.3%)
Renal and urinary disorders
Renal and urinary disorders	1/155 (0.6%)		5/153 (3.3%)
Reproductive system and breast disorders
Reproductive system and breast disorders	10/155 (6.5%)		5/153 (3.3%)
Respiratory, thoracic and mediastinal disorders
Respiratory, thoracic and mediastinal disorders	21/155 (13.5%)		18/153 (11.8%)
Skin and subcutaneous tissue disorders
Skin and subcutaneous tissue disorders	79/155 (51%)		71/153 (46.4%)
Vascular disorders
Vascular disorders	14/155 (9%)		8/153 (5.2%)

Limitations/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.