SPI-2012 vs Pegfilgrastim in the Management of Neutropenia in Participants With Breast Cancer With Docetaxel and Cyclophosphamide (ADVANCE)

• Sponsor: Spectrum Pharmaceuticals, Inc (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02643420
• Collaborator: (none)
• Enrollment: 406
• Locations: 81
• Arms: 2
• Actual Duration (Months): 33.4
• Patients Per Site: 5
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The purpose of this study was to compare the efficacy of a single dose of SPI-2012 versus pegfilgrastim in participants with early-stage breast cancer receiving docetaxel and cyclophosphamide (TC), as measured by the duration of severe neutropenia (DSN) in Cycle 1.

Condition or Disease	Intervention/Treatment	Phase
Neutropenia; Breast Cancer	Drug: SPI-2012; Drug: Pegfilgrastim; Drug: Docetaxel; Drug: Cyclophosphamide	Phase 3

Detailed Description

This was a Phase 3, randomized, open-label, active-controlled, multicenter study to compare the efficacy and safety of SPI-2012 vs pegfilgrastim in participants with breast cancer treated with TC chemotherapy.

Each cycle was 21 days. Four cycles were evaluated in this study. On Day 1 of each cycle, participants received TC chemotherapy. On Day 2 of each cycle, participants received study drug (SPI-2012 or pegfilgrastim).

Study Design

• Study Type: Interventional
• Actual Enrollment: 406 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: RAnDomized Trial of SPI-2012 Versus Pegfilgrastim in the Management of Chemotherapy Induced Neutropenia in Breast CANCEr Patients Receiving Docetaxel and Cyclophosphamide (TC) (ADVANCE)
• Actual Study Start Date: Jan 19, 2016
• Actual Primary Completion Date: Jan 24, 2018
• Actual Study Completion Date: Oct 31, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm 1: SPI-2012 and Docetaxel + Cyclophosphamide (TC) Participants received SPI-2012 13.2 milligram (mg)/0.6 milliliter (mL) (3.6 mg Granulocyte Colony-Stimulating Factor [G-CSF]) fixed-dose subcutaneous (SC) injection once per cycle on Day 2 of each cycle up to Cycle 4 (each cycle was 21 days), approximately 24-26 hours after TC chemotherapy administration. TC chemotherapy was administered on Day 1 of each cycle and included Docetaxel 75 mg/m^2 intravenous (IV) infusion and Cyclophosphamide 600 mg/m^2 IV infusion per institute's standard of care.	Drug: SPI-2012; Single-use syringes for subcutaneous injection, administered on Day 2 of each cycle; Other Names: Rolontis® Eflapegrastim (HM10460A) ; Drug: Docetaxel; Standard therapy; Other Names: Taxotere ; Drug: Cyclophosphamide; Standard therapy; Other Names: Cytoxan
Experimental: Arm 2: Pegfilgrastim and Docetaxel + Cyclophosphamide (TC) Participants received pegfilgrastim 6 mg SC injection once per cycle on Day 2 of each cycle up to Cycle 4 (each cycle was 21 days), approximately 24-26 hours after TC chemotherapy administration. TC chemotherapy on Day 1 of each cycle included Docetaxel 75 mg/m^2 IV infusion and Cyclophosphamide 600 mg/m^2 IV infusion per institute's standard of care.	Drug: Pegfilgrastim; Single-dose subcutaneous injection administered on Day 2 of each cycle; Other Names: Neulasta® ; Drug: Docetaxel; Standard therapy; Other Names: Taxotere ; Drug: Cyclophosphamide; Standard therapy; Other Names: Cytoxan

Outcome Measures

Primary Outcome Measures

1. Duration of Severe Neutropenia (DSN) in Cycle 1 [Day 1 and Days 4-15 in Cycle 1 (each cycle was 21 days)]

   DSN was defined as the number of days of severe neutropenia (absolute neutrophil count [ANC] <0.5×10^9/L), after the administration of study drug in Cycle 1.

Secondary Outcome Measures

1. Time to Absolute Neutrophil Count (ANC) Recovery in Cycle 1 [Day 1 and Days 4, 15 in Cycle 1 (each cycle was 21 days)]

   Time to ANC Recovery was defined as the time from chemotherapy administration until ANC increased to ≥1.5×10^9/L after the expected nadir within Cycle 1. Time to ANC recovery was assigned as 0 for participants whose ANC value never dropped below 1.5 x10^9/L.

2. Depth of Absolute Neutrophil Count (ANC) Nadir in Cycle 1 [Day 1 and Days 4, 15 in Cycle 1 (each cycle was 21 days)]

   Depth of ANC Nadir was defined as the lowest ANC value after administration of study drug (SPI-2012 or Pegfilgrastim) in Cycle 1.

3. Number of Participants With Febrile Neutropenia (FN) in Cycle 1 [Day 1 and Days 4, 15 in Cycle 1 (each cycle was 21 days)]

   FN was defined as an oral temperature > 38.3 degrees Celsius (C) (101.0 degrees Fahrenheit [F]) or two consecutive readings of >=38.0 degrees C (100.4 degrees F) for 2 hours and ANC <1.0×10^9/L.

4. Duration of Severe Neutropenia in Cycle 2, 3 and 4 [Days 1, 4, 7, 10, and 15 in cycles 2, 3, and 4 (each cycle was 21 days)]

   DSN was defined as the number of days of severe neutropenia (ANC <0.5×10^9 /L) from the first occurrence of an ANC below the threshold in Cycles 2, 3, and 4.

5. Number of Participants With Neutropenic Complications in Cycle 1 [Day 1 and Days 4, 15 in Cycle 1 (each cycle was 21 days)]

   Neutropenic complications refer to hospitalizations due to neutropenic events and/or the use of anti-infectives due to neutropenia.

6. Number of Participants With Febrile Neutropenia in Cycles 2, 3, and 4 [Days 1, 4, 7, 10, and 15 of Cycles 2, 3, and 4 (each cycle was 21 days)]

   FN was defined as an oral temperature > 38.3 degrees C (101.0 degrees Fahrenheit [F]) or two consecutive readings of >=38.0 degrees C (100.4 degrees F) for 2 hours and ANC <1.0×10^9/L.

7. Relative Dose Intensity (RDI) of TC (Docetaxel + Cyclophosphamide) in Cycles 1 to 4 [Cycles 1 to 4 (each cycle was 21 days)]

   RDI was defined as the percentage of the planned dose that each participant actually received during the study, expressed as the total dose received, divided by the total dose planned and multiplied by 100. The planned dose was defined as the dose that would be given if no doses were missed and/or no dose reductions were made for the number of cycles started. The total planned dose was the sum of planned doses over all cycles.

8. Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) [From the first dose of TC (Docetaxel + Cyclophosphamide) until 12 months after the last dose of study treatment (up to approximately 34 months)]

   An adverse event (AE) is defined as any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product or study procedure, whether or not considered related to the medicinal product. A TEAE for Treatment Period is defined as adverse event with an onset date on or after the date of study drug administration through the end of treatment. TEAE for follow up is defined as any new onset or ongoing AE at the end of Treatment. SAE is defined as any AE which meets any of the following criteria: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in a persistent or significant disability/incapacity, results in a congenital anomaly/birth defect, includes important medical events.

Eligibility Criteria

Criteria

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

Key Inclusion Criteria:

• New diagnosis of histologically confirmed early-stage breast cancer (ESBC), defined as operable Stage I to Stage IIIA breast cancer

• Candidate for adjuvant or neoadjuvant TC chemotherapy

• Eastern Cooperative Oncology Group (ECOG) performance score ≤ 2

• Absolute neutrophil count (ANC) ≥ 1.5×10^9/L

• Platelet count ≥ 100×10^9/L

• Hemoglobin > 9 g/dL

• Creatinine clearance > 50 mL/min

• Total bilirubin ≤ 1.5 mg/dL

• Aspartate Aminotransferase per Serum Glutamic-Oxaloacetic Transaminase (AST/SGOT) and Alanine Aminotransferase per Serum Glutamic-Pyruvic Transaminase (ALT/SGPT) ≤ 2.5× Upper Limit of Normal (ULN).

• Alkaline phosphatase ≤ 2.0×ULN

Key Exclusion Criteria:

• Active concurrent malignancy (except non-melanoma skin cancer or carcinoma in situ of the cervix) or life-threatening disease

• Locally recurrent or metastatic breast cancer

• Known sensitivity to E. coli -derived products or to any products to be administered during dosing

• Concurrent adjuvant cancer therapy

• Previous exposure to filgrastim, pegfilgrastim, or other G-CSF products in clinical development within 12 months prior to the administration of study drug

• Active infection, receiving anti-infectives, or any serious underlying medical condition that would impair ability to receive protocol treatment

• Prior bone marrow or stem cell transplant

• Use of any investigational drugs, biologics, or devices within 30 days prior to study treatment or plans to use any of these during the course of the study

• Radiation therapy within 30 days prior to enrollment

• Major surgery within 30 days prior to enrollment

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Arizona Center for Cancer Care	Glendale	Arizona	United States	85306
2	Arizona Clinical Research Center/ ACRC	Tucson	Arizona	United States	85715
3	Yuma Regional Medical Center	Yuma	Arizona	United States	85364
4	Genesis Cancer Center	Hot Springs	Arkansas	United States	71913
5	NEA Baptist Clinic | Fowler Family Center for Cancer Care	Jonesboro	Arkansas	United States	72401
6	Pacific Cancer Medical Center, Inc.	Anaheim	California	United States	92801
7	CBCC Global Research, Inc. at Comprehensive Blood and Cancer Center	Bakersfield	California	United States	93309
8	Alta Bates Summit Medical Center	Berkeley	California	United States	94704
9	Precision Research Institute, LLC	Chula Vista	California	United States	91910
10	Compassionate Cancer Care Medical Group, Inc.	Corona	California	United States	92879
11	Compassionate Care Research Group, Inc.	Fountain Valley	California	United States	92708
12	Long Beach Memorial Medical Center	Long Beach	California	United States	90806
13	Pacific Shores Medical Group	Long Beach	California	United States	90813
14	Ventura County Hematology-Oncology Specialists	Oxnard	California	United States	93030
15	Valley Medical Oncology Consultants	Pleasanton	California	United States	94588
16	Emad Ibrahim, MD, Inc.	Redlands	California	United States	92373
17	Compassionate Cancer Care Medical Group, Inc	Riverside	California	United States	92501
18	St Joseph Heritage Healthcare Institution	Santa Rosa	California	United States	95403
19	Wellness Oncology Hematology	West Hills	California	United States	91307
20	Oncology Institute of Hope and Innovation	Whittier	California	United States	90603
21	Omega Research Consultants LLC	DeBary	Florida	United States	32713
22	Pasco Pinellas Cancer Center	Holiday	Florida	United States	34691
23	Lakes Research, LLC	Miami Lakes	Florida	United States	33014
24	AMPM Research Clinic	Miami	Florida	United States	33133
25	Mid Florida Hematology and Oncology Centers	Orange City	Florida	United States	32763
26	Florida Cancer Research Institute	Plantation	Florida	United States	33324
27	Bond Clinic, P.A.	Winter Haven	Florida	United States	33881
28	John B Amos Cancer Center	Columbus	Georgia	United States	31904
29	Dwight D. Eisenhower Army Medical Center	Fort Gordon	Georgia	United States	30905
30	Memorial Health University Medical Center	Savannah	Georgia	United States	31404
31	Saint Alphonsus Regional Medical Center	Boise	Idaho	United States	83706
32	Clintell, Inc/Swedish Covenant Hospital	Chicago	Illinois	United States	60625
33	Joliet Oncology Hematology Associates	Joliet	Illinois	United States	60435
34	Oncology Specialists, SC	Park Ridge	Illinois	United States	60068
35	Swedish American Cancer Center	Rockford	Illinois	United States	61114
36	Carle Cancer Center	Urbana	Illinois	United States	61801
37	Franciscan St. Francis Health	Indianapolis	Indiana	United States	46237
38	Floyd Memorial Cancer Center of Indiana	New Albany	Indiana	United States	47150
39	Northern Indiana Cancer Research Consortium	Westville	Indiana	United States	46391
40	Ashland-Bellefonte Cancer Center	Ashland	Kentucky	United States	41101
41	West Ky Hematology & Oncology Group, PSC	Paducah	Kentucky	United States	42003
42	Pontchartrain Cancer Center	Covington	Louisiana	United States	70433
43	Highland Clinic	Shreveport	Louisiana	United States	71105
44	Penobscot Bay Medical Center	Rockport	Maine	United States	04856
45	RCCA MD LLC/The Center for Cancer and Blood Disorders	Bethesda	Maryland	United States	20817
46	Reliant Medical Group	Worcester	Massachusetts	United States	01608v
47	Quest Research Institute	Royal Oak	Michigan	United States	48073
48	Forrest General Hospital	Hattiesburg	Mississippi	United States	39401
49	Freeman Health Systems	Joplin	Missouri	United States	64804
50	St. Vincent Frontier Cancer Center	Billings	Montana	United States	59102
51	Saint Francis Cancer Treatment Center	Grand Island	Nebraska	United States	68803
52	Southeast Nebraska Hematology & Oncology Consultants, PC	Lincoln	Nebraska	United States	68510
53	New Jersey Hematology Oncology Associates	Brick	New Jersey	United States	08724
54	North Shore Hematology Oncology Associates	East Setauket	New York	United States	11733
55	Waverly Hematology Oncology	Cary	North Carolina	United States	27518
56	Aultman Hospital	Canton	Ohio	United States	44710
57	Gabrail Cancer Center Research	Canton	Ohio	United States	44718
58	The Lindner Research Center at the Christ Hospital	Cincinnati	Ohio	United States	45219
59	Mercy Health Youngstown LLC DBA	Youngstown	Ohio	United States	44504 44501
60	Good Samaritan Hospital Corvallis	Corvallis	Oregon	United States	97330
61	University of Pittsburgh Medical Center (UPMC)	Pittsburgh	Pennsylvania	United States	15232
62	Associates in Hematology and Oncology, PC	Upland	Pennsylvania	United States	19013
63	AnMed Health Cancer Center	Anderson	South Carolina	United States	29621
64	Bon Secours Saint Francis Cancer	Greenville	South Carolina	United States	29607
65	Carolina Blood and Cancer Care	Rock Hill	South Carolina	United States	29732
66	Cookeville Regional Medical Center	Cookeville	Tennessee	United States	38501
67	The West Clinic, PC, d/b/a West Cancer Center	Germantown	Tennessee	United States	38138
68	CHI St. Joseph Health Cancer Center	Bryan	Texas	United States	77802
69	Texas Oncology -Methodist Dallas Cancer Center	Dallas	Texas	United States	75203
70	Oncology Consultants	Houston	Texas	United States	77030
71	Texas Oncology, PA	McAllen	Texas	United States	78503
72	Methodist Richardson Medical Center- Cancer Center	Richardson	Texas	United States	75082
73	Northern Utah Associates	Ogden	Utah	United States	84403
74	Delta Oncology Associates	Portsmouth	Virginia	United States	23704
75	Northwest Medical Specialties, PLLC	Tacoma	Washington	United States	98405
76	West Virginia University	Morgantown	West Virginia	United States	26506
77	CISSS de la Montérégie-Centre	Greenfield Park	Quebec	Canada	J4V 2H1
78	Jewish General Hospital	Montreal	Quebec	Canada	H3T 1E2
79	CHU de Quebec - Universite Laval	Québec	Quebec	Canada	G1S 4L8
80	Cha Bundang Medical Center	Seongnam-si	Gyeonggi-do	Korea, Republic of	13496
81	Severance Hospital	Sinchon-dong	Seoul	Korea, Republic of	03722

Sponsors and Collaborators

• Spectrum Pharmaceuticals, Inc

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Jan 26, 2017
• Statistical Analysis Plan - Jul 31, 2018

More Information

Publications

None provided.

• Responsible Party: Spectrum Pharmaceuticals, Inc
• ClinicalTrials.gov Identifier: NCT02643420
• Other Study ID Numbers: SPI-GCF-301
• First Posted: Dec 31, 2015
• Last Update Posted: Mar 2, 2022
• Last Verified: Feb 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Spectrum Pharmaceuticals, Inc: Neutropenia; Breast Cancer; Long-acting Myeloid Growth Factor; Early Stage Breast Cancer; Docetaxel + Cyclophosphamide (TC) chemotherapy
• Additional relevant MeSH terms: Breast Neoplasms; Neutropenia; Cyclophosphamide; Docetaxel

Study Results

Participant Flow

Recruitment Details	Participants were enrolled from 19 Jan 2016 to 31 Oct 2018. A total of 406 participants were randomized in the study.

Arm/Group Title	Arm 1: SPI-2012 and Docetaxel + Cyclophosphamide (TC)	Arm 2: Pegfilgrastim and Docetaxel + Cyclophosphamide (TC)
Arm/Group Description	Participants received SPI-2012 13.2 milligram (mg)/0.6 milliliter (mL) (3.6 mg Granulocyte Colony-Stimulating Factor [G-CSF]) fixed-dose subcutaneous (SC) injection once per cycle on Day 2 of each cycle up to Cycle 4 (each cycle was 21 days), approximately 24-26 hours after TC chemotherapy administration. TC chemotherapy was administered on Day 1 of each cycle and included Docetaxel 75 mg/m^2 intravenous (IV) infusion and Cyclophosphamide 600 mg/m^2 IV infusion per institute's standard of care.	Participants received pegfilgrastim 6 mg SC injection once per cycle on Day 2 of each cycle up to Cycle 4 (each cycle was 21 days), approximately 24-26 hours after TC chemotherapy administration. TC chemotherapy on Day 1 of each cycle included Docetaxel 75 mg/m^2 IV infusion and Cyclophosphamide 600 mg/m^2 IV infusion per institute's standard of care.
Period Title: Overall Study
STARTED	196	210
Safety Population	197	208
COMPLETED	142	145
NOT COMPLETED	54	65

Baseline Characteristics

Arm/Group Title	Arm 1: SPI-2012 and TC	Arm 2: Pegfilgrastim and TC	Total
Arm/Group Description	Participants received SPI-2012 13.2 mg/0.6mL (3.6 mg G-CSF) fixed-dose SC injection once per cycle on Day 2 of each cycle up to Cycle 4 (each cycle was 21 days), approximately 24-26 hours after TC chemotherapy administration. TC chemotherapy was administered on Day 1 of each cycle and included Docetaxel 75 mg/m^2 IV infusion and Cyclophosphamide 600 mg/m^2 IV infusion per institute's standard of care.	Participants received pegfilgrastim 6 mg SC injection once per cycle on Day 2 of each cycle up to Cycle 4 (each cycle was 21 days), approximately 24-26 hours after TC chemotherapy administration. TC chemotherapy on Day 1 of each cycle included Docetaxel 75 mg/m^2 IV infusion and Cyclophosphamide 600 mg/m^2 IV infusion per institute's standard of care.	Total of all reporting groups
Overall Participants	196	210	406
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	59.9 (11.12)	59.0 (11.79)	59.5 (11.47)
Sex: Female, Male (Count of Participants)
Female	195 99.5%	209 99.5%	404 99.5%
Male	1 0.5%	1 0.5%	2 0.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	34 17.3%	40 19%	74 18.2%
Not Hispanic or Latino	162 82.7%	170 81%	332 81.8%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (Count of Participants)
White or Caucasian	156 79.6%	159 75.7%	315 77.6%
Black or African American	26 13.3%	32 15.2%	58 14.3%
Asian	9 4.6%	9 4.3%	18 4.4%
American Indian or Alaska Native	1 0.5%	1 0.5%	2 0.5%
Native Hawaiian or Other Pacific Islander	0 0%	1 0.5%	1 0.2%
Other	4 2%	8 3.8%	12 3%

Outcome Measures

1. Primary Outcome

Title	Duration of Severe Neutropenia (DSN) in Cycle 1
Description	DSN was defined as the number of days of severe neutropenia (absolute neutrophil count [ANC] <0.5×10^9/L), after the administration of study drug in Cycle 1.
Time Frame	Day 1 and Days 4-15 in Cycle 1 (each cycle was 21 days)

Outcome Measure Data

Analysis Population Description

The ITT population included all participants who were randomized.

Arm/Group Title	Arm 1: SPI-2012 and TC	Arm 2: Pegfilgrastim and TC
Arm/Group Description	Participants received SPI-2012 13.2 mg/0.6mL (3.6 mg G-CSF) fixed-dose SC injection once per cycle on Day 2 of each cycle up to Cycle 4 (each cycle was 21 days), approximately 24-26 hours after TC chemotherapy administration. TC chemotherapy was administered on Day 1 of each cycle and included Docetaxel 75 mg/m^2 IV infusion and Cyclophosphamide 600 mg/m^2 IV infusion per institute's standard of care.	Participants received pegfilgrastim 6 mg SC injection once per cycle on Day 2 of each cycle up to Cycle 4 (each cycle was 21 days), approximately 24-26 hours after TC chemotherapy administration. TC chemotherapy on Day 1 of each cycle included Docetaxel 75 mg/m^2 IV infusion and Cyclophosphamide 600 mg/m^2 IV infusion per institute's standard of care.
Measure Participants	196	210
Mean (Standard Deviation) [days]	0.20 (0.503)	0.35 (0.683)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm 1: SPI-2012 and TC, Arm 2: Pegfilgrastim and TC
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	The margin of non-inferiority to be used in the study is 0.62 day. The non-inferiority of SPI-2012 to Pegfilgrastim was declared if the upper bound of 95% confidence interval (CI) of the difference in mean DSN between the treatment arms was <0.62 days.
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	t-statistics
	Comments	The p-values are based on the calculated t-statistics from the bootstrapped sample mean and standard deviation.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.148
	Confidence Interval	(2-Sided) 95%; -0.266 to -0.031
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Time to Absolute Neutrophil Count (ANC) Recovery in Cycle 1
Description	Time to ANC Recovery was defined as the time from chemotherapy administration until ANC increased to ≥1.5×10^9/L after the expected nadir within Cycle 1. Time to ANC recovery was assigned as 0 for participants whose ANC value never dropped below 1.5 x10^9/L.
Time Frame	Day 1 and Days 4, 15 in Cycle 1 (each cycle was 21 days)

Outcome Measure Data

Analysis Population Description

The ITT population included all participants who were randomized.

Arm/Group Title	Arm 1: SPI-2012 and TC	Arm 2: Pegfilgrastim and TC
Arm/Group Description	Participants received SPI-2012 13.2 mg/0.6mL (3.6 mg G-CSF) fixed-dose SC injection once per cycle on Day 2 of each cycle up to Cycle 4 (each cycle was 21 days), approximately 24-26 hours after TC chemotherapy administration. TC chemotherapy was administered on Day 1 of each cycle and included Docetaxel 75 mg/m^2 IV infusion and Cyclophosphamide 600 mg/m^2 IV infusion per institute's standard of care.	Participants received pegfilgrastim 6 mg SC injection once per cycle on Day 2 of each cycle up to Cycle 4 (each cycle was 21 days), approximately 24-26 hours after TC chemotherapy administration. TC chemotherapy on Day 1 of each cycle included Docetaxel 75 mg/m^2 IV infusion and Cyclophosphamide 600 mg/m^2 IV infusion per institute's standard of care.
Measure Participants	196	210
Mean (Standard Deviation) [days]	3.24 (3.565)	3.49 (3.589)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm 1: SPI-2012 and TC, Arm 2: Pegfilgrastim and TC
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.685
	Comments
	Method	Negative binomial regression
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.25
	Confidence Interval	(2-Sided) 95%; -1.43 to 0.94
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Depth of Absolute Neutrophil Count (ANC) Nadir in Cycle 1
Description	Depth of ANC Nadir was defined as the lowest ANC value after administration of study drug (SPI-2012 or Pegfilgrastim) in Cycle 1.
Time Frame	Day 1 and Days 4, 15 in Cycle 1 (each cycle was 21 days)

Outcome Measure Data

Analysis Population Description

The ITT population included all participants who were randomized. Here, Overall number of participants analyzed signifies participants who were evaluable for this outcome measure.

Arm/Group Title	Arm 1: SPI-2012 and TC	Arm 2: Pegfilgrastim and TC
Arm/Group Description	Participants received SPI-2012 13.2 mg/0.6mL (3.6 mg G-CSF) fixed-dose SC injection once per cycle on Day 2 of each cycle up to Cycle 4 (each cycle was 21 days), approximately 24-26 hours after TC chemotherapy administration. TC chemotherapy was administered on Day 1 of each cycle and included Docetaxel 75 mg/m^2 IV infusion and Cyclophosphamide 600 mg/m^2 IV infusion per institute's standard of care.	Participants received pegfilgrastim 6 mg SC injection once per cycle on Day 2 of each cycle up to Cycle 4 (each cycle was 21 days), approximately 24-26 hours after TC chemotherapy administration. TC chemotherapy on Day 1 of each cycle included Docetaxel 75 mg/m^2 IV infusion and Cyclophosphamide 600 mg/m^2 IV infusion per institute's standard of care.
Measure Participants	191	196
Mean (Standard Deviation) [10^9 ANC/L]	2.56 (3.086)	2.53 (3.317)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm 1: SPI-2012 and TC, Arm 2: Pegfilgrastim and TC
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.155
	Comments
	Method	Asymptotic normality assumption
	Comments	P-value was obtained based upon asymptotic normality assumption on the log10 transformed data.
Method of Estimation	Estimation Parameter	Median Difference (Final Values)
	Estimated Value	1.2
	Confidence Interval	(2-Sided) 95%; 0.93 to 1.56
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Number of Participants With Febrile Neutropenia (FN) in Cycle 1
Description	FN was defined as an oral temperature > 38.3 degrees Celsius (C) (101.0 degrees Fahrenheit [F]) or two consecutive readings of >=38.0 degrees C (100.4 degrees F) for 2 hours and ANC <1.0×10^9/L.
Time Frame	Day 1 and Days 4, 15 in Cycle 1 (each cycle was 21 days)

Outcome Measure Data

Analysis Population Description

The ITT population included all participants who were randomized.

Arm/Group Title	Arm 1: SPI-2012 and TC	Arm 2: Pegfilgrastim and TC
Arm/Group Description	Participants received SPI-2012 13.2 mg/0.6mL (3.6 mg G-CSF) fixed-dose SC injection once per cycle on Day 2 of each cycle up to Cycle 4 (each cycle was 21 days), approximately 24-26 hours after TC chemotherapy administration. TC chemotherapy was administered on Day 1 of each cycle and included Docetaxel 75 mg/m^2 IV infusion and Cyclophosphamide 600 mg/m^2 IV infusion per institute's standard of care.	Participants received pegfilgrastim 6 mg SC injection once per cycle on Day 2 of each cycle up to Cycle 4 (each cycle was 21 days), approximately 24-26 hours after TC chemotherapy administration. TC chemotherapy on Day 1 of each cycle included Docetaxel 75 mg/m^2 IV infusion and Cyclophosphamide 600 mg/m^2 IV infusion per institute's standard of care.
Measure Participants	196	210
Count of Participants [Participants]	4 2%	2 1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm 1: SPI-2012 and TC, Arm 2: Pegfilgrastim and TC
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.435
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Percent Difference
	Estimated Value	1.1
	Confidence Interval	(2-Sided) 95%; -8.6 to 10.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Duration of Severe Neutropenia in Cycle 2, 3 and 4
Description	DSN was defined as the number of days of severe neutropenia (ANC <0.5×10^9 /L) from the first occurrence of an ANC below the threshold in Cycles 2, 3, and 4.
Time Frame	Days 1, 4, 7, 10, and 15 in cycles 2, 3, and 4 (each cycle was 21 days)

Outcome Measure Data

Analysis Population Description

The ITT population included all participants who were randomized.

Arm/Group Title	Arm 1: SPI-2012 and TC	Arm 2: Pegfilgrastim and TC
Arm/Group Description	Participants received SPI-2012 13.2 mg/0.6mL (3.6 mg G-CSF) fixed-dose SC injection once per cycle on Day 2 of each cycle up to Cycle 4 (each cycle was 21 days), approximately 24-26 hours after TC chemotherapy administration. TC chemotherapy was administered on Day 1 of each cycle and included Docetaxel 75 mg/m^2 IV infusion and Cyclophosphamide 600 mg/m^2 IV infusion per institute's standard of care.	Participants received pegfilgrastim 6 mg SC injection once per cycle on Day 2 of each cycle up to Cycle 4 (each cycle was 21 days), approximately 24-26 hours after TC chemotherapy administration. TC chemotherapy on Day 1 of each cycle included Docetaxel 75 mg/m^2 IV infusion and Cyclophosphamide 600 mg/m^2 IV infusion per institute's standard of care.
Measure Participants	196	210
Cycle 2	0.13 (0.383)	0.09 (0.374)
Cycle 3	0.11 (0.326)	0.08 (0.273)
Cycle 4	0.11 (0.362)	0.09 (0.281)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm 1: SPI-2012 and TC, Arm 2: Pegfilgrastim and TC
	Comments	DSN in Cycle 2
	Type of Statistical Test	Non-Inferiority
	Comments	The margin of non-inferiority to be used in the study is 0.62 day. The non-inferiority of SPI-2012 to Pegfilgrastim was declared if the upper bound of 95% CI of the difference in mean DSN between the treatment arms was <0.62 days.
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	t-statistics
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.042
	Confidence Interval	(2-Sided) 95%; -0.032 to 0.116
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Arm 1: SPI-2012 and TC, Arm 2: Pegfilgrastim and TC
	Comments	DSN in Cycle 3
	Type of Statistical Test	Non-Inferiority
	Comments	The margin of non-inferiority to be used in the study is 0.62 day. The non-inferiority of SPI-2012 to Pegfilgrastim was declared if the upper bound of 95% CI of the difference in mean DSN between the treatment arms was <0.62 days.
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	t-statistics
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.026
	Confidence Interval	(2-Sided) 95%; -0.032 to 0.085
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Arm 1: SPI-2012 and TC, Arm 2: Pegfilgrastim and TC
	Comments	DSN in Cycle 4
	Type of Statistical Test	Non-Inferiority
	Comments	The margin of non-inferiority to be used in the study is 0.62 day. The non-inferiority of SPI-2012 to Pegfilgrastim was declared if the upper bound of 95% CI of the difference in mean DSN between the treatment arms was <0.62 days.
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	t-statistics
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.027
	Confidence Interval	(2-Sided) 95%; -0.036 to 0.089
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Number of Participants With Neutropenic Complications in Cycle 1
Description	Neutropenic complications refer to hospitalizations due to neutropenic events and/or the use of anti-infectives due to neutropenia.
Time Frame	Day 1 and Days 4, 15 in Cycle 1 (each cycle was 21 days)

Outcome Measure Data

Analysis Population Description

The ITT population included all participants who was randomized.

Arm/Group Title	Arm 1: SPI-2012 and TC	Arm 2: Pegfilgrastim and TC
Arm/Group Description	Participants received SPI-2012 13.2 mg/0.6mL (3.6 mg G-CSF) fixed-dose SC injection once per cycle on Day 2 of each cycle up to Cycle 4 (each cycle was 21 days), approximately 24-26 hours after TC chemotherapy administration. TC chemotherapy was administered on Day 1 of each cycle and included Docetaxel 75 mg/m^2 IV infusion and Cyclophosphamide 600 mg/m^2 IV infusion per institute's standard of care.	Participants received pegfilgrastim 6 mg SC injection once per cycle on Day 2 of each cycle up to Cycle 4 (each cycle was 21 days), approximately 24-26 hours after TC chemotherapy administration. TC chemotherapy on Day 1 of each cycle included Docetaxel 75 mg/m^2 IV infusion and Cyclophosphamide 600 mg/m^2 IV infusion per institute's standard of care.
Measure Participants	196	210
Count of Participants [Participants]	8 4.1%	8 3.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm 1: SPI-2012 and TC, Arm 2: Pegfilgrastim and TC
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	1.000
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Percent Difference
	Estimated Value	0.3
	Confidence Interval	(2-Sided) 95%; -9.5 to 10.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Number of Participants With Febrile Neutropenia in Cycles 2, 3, and 4
Description	FN was defined as an oral temperature > 38.3 degrees C (101.0 degrees Fahrenheit [F]) or two consecutive readings of >=38.0 degrees C (100.4 degrees F) for 2 hours and ANC <1.0×10^9/L.
Time Frame	Days 1, 4, 7, 10, and 15 of Cycles 2, 3, and 4 (each cycle was 21 days)

Outcome Measure Data

Analysis Population Description

The ITT population included all participants who were randomized

Arm/Group Title	Arm 1: SPI-2012 and TC	Arm 2: Pegfilgrastim and TC
Arm/Group Description	Participants received SPI-2012 13.2 mg/0.6mL (3.6 mg G-CSF) fixed-dose SC injection once per cycle on Day 2 of each cycle up to Cycle 4 (each cycle was 21 days), approximately 24-26 hours after TC chemotherapy administration. TC chemotherapy was administered on Day 1 of each cycle and included Docetaxel 75 mg/m^2 IV infusion and Cyclophosphamide 600 mg/m^2 IV infusion per institute's standard of care.	Participants received pegfilgrastim 6 mg SC injection once per cycle on Day 2 of each cycle up to Cycle 4 (each cycle was 21 days), approximately 24-26 hours after TC chemotherapy administration. TC chemotherapy on Day 1 of each cycle included Docetaxel 75 mg/m^2 IV infusion and Cyclophosphamide 600 mg/m^2 IV infusion per institute's standard of care.
Measure Participants	196	210
Cycle 2	1 0.5%	1 0.5%
Cycle 3	4 2%	1 0.5%
Cycle 4	2 1%	0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm 1: SPI-2012 and TC, Arm 2: Pegfilgrastim and TC
	Comments	FN in Cycle 2
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	1.000
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Percent Difference
	Estimated Value	0.0
	Confidence Interval	(2-Sided) 95%; -9.7 to 9.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Arm 1: SPI-2012 and TC, Arm 2: Pegfilgrastim and TC
	Comments	FN in Cycle 3
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.201
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Percent Difference
	Estimated Value	1.6
	Confidence Interval	(2-Sided) 95%; -8.2 to 11.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Arm 1: SPI-2012 and TC, Arm 2: Pegfilgrastim and TC
	Comments	FN in Cycle 4
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.232
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Percent Difference
	Estimated Value	1.0
	Confidence Interval	(2-Sided) 95%; -8.7 to 10.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Secondary Outcome

Title	Relative Dose Intensity (RDI) of TC (Docetaxel + Cyclophosphamide) in Cycles 1 to 4
Description	RDI was defined as the percentage of the planned dose that each participant actually received during the study, expressed as the total dose received, divided by the total dose planned and multiplied by 100. The planned dose was defined as the dose that would be given if no doses were missed and/or no dose reductions were made for the number of cycles started. The total planned dose was the sum of planned doses over all cycles.
Time Frame	Cycles 1 to 4 (each cycle was 21 days)

Outcome Measure Data

Analysis Population Description

Safety Population included all participants who received at least one dose of any protocol-specified drug (TC, SPI-2012 or pegfilgrastim). One participant was randomized to pegfilgrastim but was given SPI-2012 in Safety Population.

Arm/Group Title	Arm 1: SPI-2012 and TC	Arm 2: Pegfilgrastim and TC
Arm/Group Description	Participants received SPI-2012 13.2 mg/0.6mL (3.6 mg G-CSF) fixed-dose SC injection once per cycle on Day 2 of each cycle up to Cycle 4 (each cycle was 21 days), approximately 24-26 hours after TC chemotherapy administration. TC chemotherapy was administered on Day 1 of each cycle and included Docetaxel 75 mg/m^2 IV infusion and Cyclophosphamide 600 mg/m^2 IV infusion per institute's standard of care.	Participants received pegfilgrastim 6 mg SC injection once per cycle on Day 2 of each cycle up to Cycle 4 (each cycle was 21 days), approximately 24-26 hours after TC chemotherapy administration. TC chemotherapy on Day 1 of each cycle included Docetaxel 75 mg/m^2 IV infusion and Cyclophosphamide 600 mg/m^2 IV infusion per institute's standard of care.
Measure Participants	197	208
Docetaxel	99.1 (5.47)	98.1 (8.45)
Cyclophosphamide	99.3 (3.86)	99.0 (4.33)

9. Secondary Outcome

Title	Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Description	An adverse event (AE) is defined as any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product or study procedure, whether or not considered related to the medicinal product. A TEAE for Treatment Period is defined as adverse event with an onset date on or after the date of study drug administration through the end of treatment. TEAE for follow up is defined as any new onset or ongoing AE at the end of Treatment. SAE is defined as any AE which meets any of the following criteria: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in a persistent or significant disability/incapacity, results in a congenital anomaly/birth defect, includes important medical events.
Time Frame	From the first dose of TC (Docetaxel + Cyclophosphamide) until 12 months after the last dose of study treatment (up to approximately 34 months)

Outcome Measure Data

Analysis Population Description

Safety Population included all participants who received at least one dose of any protocol-specified drug (TC, SPI-2012 or pegfilgrastim). One participant was randomized to pegfilgrastim but was given SPI-2012 in Safety Population. Data was summarized and reported separately for Treatment Period and Follow-up Period.

Arm/Group Title	Arm 1: SPI-2012 and TC -Treatment Period	Arm 2: Pegfilgrastim and TC -Treatment Period	Arm 1: SPI-2012 and TC - Follow up Period	Arm 2: Pegfilgrastim and TC - Follow up Period
Arm/Group Description	Participants received SPI-2012 13.2 mg/0.6mL (3.6 mg G-CSF) fixed-dose SC injection once per cycle on Day 2 of each cycle up to Cycle 4 (each cycle was 21 days), approximately 24-26 hours after TC chemotherapy administration. TC chemotherapy was administered on Day 1 of each cycle and included Docetaxel 75 mg/m^2 IV infusion and Cyclophosphamide 600 mg/m^2 IV infusion per institute's standard of care. All participants were followed for 35 (±5) days after the last study treatment or patient discontinuation.	Participants received Pegfilgrastim 6 mg SC injection once per cycle on Day 2 of each cycle up to Cycle 4 (each cycle was 21 days), approximately 24-26 hours after TC chemotherapy administration. TC chemotherapy was administered on Day 1 of each cycle and included Docetaxel 75 mg/m^2 IV infusion and Cyclophosphamide 600 mg/m^2 IV infusion per institute's standard of care. All participants were followed for 35 (±5) days after the last study treatment or patient discontinuation.	In addition to the treatment period, long-term safety follow-up continued for 12 months after last dose of study treatment.	In addition to the treatment period, long-term safety follow-up continued for 12 months after last dose of study treatment.
Measure Participants	197	208	197	208
TEAE	192 98%	204 97.1%	95 23.4%	83 NaN
SAE	36 18.4%	29 13.8%	8 2%	2 NaN

Adverse Events

Time Frame	From the first dose of TC (Docetaxel + Cyclophosphamide) until 12 months after the last dose of study treatment (up to approximately 34 months)
Adverse Event Reporting Description	The safety population included all participants who had received at least one dose of any protocol specified drug (TC, SPI-2012, or pegfilgrastim). One participant was randomized to pegfilgrastim received SPI-2012 and was included in the Safety Population. Adverse events data was summarized and reported separately for the Treatment Period and Follow-up Period.
Arm/Group Title	Arm 1: SPI-2012 and TC -Treatment Period		Arm 2: Pegfilgrastim and TC -Treatment Period		Arm 1: SPI-2012 and TC - Follow up Period		Arm 2: Pegfilgrastim and TC - Follow up Period
Arm/Group Description	Participants received SPI-2012 13.2 mg/0.6mL (3.6 mg G-CSF) fixed-dose SC injection once per cycle on Day 2 of each cycle up to Cycle 4 (each cycle was 21 days), approximately 24-26 hours after TC chemotherapy administration. TC chemotherapy was administered on Day 1 of each cycle and included Docetaxel 75 mg/m^2 IV infusion and Cyclophosphamide 600 mg/m^2 IV infusion per institute's standard of care. All participants were followed for 35 (±5) days after the last study treatment or patient discontinuation.		Participants received Pegfilgrastim 6 mg SC injection once per cycle on Day 2 of each cycle up to Cycle 4 (each cycle was 21 days), approximately 24-26 hours after TC chemotherapy administration. TC chemotherapy was administered on Day 1 of each cycle and included Docetaxel 75 mg/m^2 IV infusion and Cyclophosphamide 600 mg/m^2 IV infusion per institute's standard of care. All participants were followed for 35 (±5) days after the last study treatment or patient discontinuation.		In addition to the treatment period, long-term safety follow-up continued for 12 months after last dose of study treatment.		In addition to the treatment period, long-term safety follow-up continued for 12 months after last dose of study treatment.
All Cause Mortality
	Arm 1: SPI-2012 and TC -Treatment Period		Arm 2: Pegfilgrastim and TC -Treatment Period		Arm 1: SPI-2012 and TC - Follow up Period		Arm 2: Pegfilgrastim and TC - Follow up Period
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/197 (0%)		1/208 (0.5%)		0/197 (0%)		1/208 (0.5%)
Serious Adverse Events
	Arm 1: SPI-2012 and TC -Treatment Period		Arm 2: Pegfilgrastim and TC -Treatment Period		Arm 1: SPI-2012 and TC - Follow up Period		Arm 2: Pegfilgrastim and TC - Follow up Period
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	36/197 (18.3%)		29/208 (13.9%)		8/197 (4.1%)		2/208 (1%)
Blood and lymphatic system disorders
Febrile neutropenia	3/197 (1.5%)		2/208 (1%)		1/197 (0.5%)		0/208 (0%)
Neutropenia	0/197 (0%)		2/208 (1%)		1/197 (0.5%)		0/208 (0%)
Cardiac disorders
Acute myocardial infarction	0/197 (0%)		0/208 (0%)		0/197 (0%)		1/208 (0.5%)
Atrial fibrillation	0/197 (0%)		2/208 (1%)		0/197 (0%)		0/208 (0%)
Cardiac arrest	0/197 (0%)		1/208 (0.5%)		0/197 (0%)		0/208 (0%)
Cardiac failure congestive	1/197 (0.5%)		1/208 (0.5%)		0/197 (0%)		0/208 (0%)
Myocardial infarction	0/197 (0%)		1/208 (0.5%)		0/197 (0%)		0/208 (0%)
Ventricular arrhythmia	1/197 (0.5%)		0/208 (0%)		0/197 (0%)		0/208 (0%)
Gastrointestinal disorders
Abdominal pain	0/197 (0%)		2/208 (1%)		1/197 (0.5%)		0/208 (0%)
Colitis	2/197 (1%)		0/208 (0%)		0/197 (0%)		0/208 (0%)
Diarrhoea	2/197 (1%)		1/208 (0.5%)		0/197 (0%)		0/208 (0%)
Gastrointestinal haemorrhage	0/197 (0%)		2/208 (1%)		0/197 (0%)		0/208 (0%)
Gastrointestinal ischaemia	0/197 (0%)		1/208 (0.5%)		0/197 (0%)		0/208 (0%)
Gastrointestinal necrosis	0/197 (0%)		1/208 (0.5%)		0/197 (0%)		0/208 (0%)
Nausea	0/197 (0%)		1/208 (0.5%)		0/197 (0%)		0/208 (0%)
Neutropenic colitis	1/197 (0.5%)		0/208 (0%)		0/197 (0%)		0/208 (0%)
Rectal haemorrhage	1/197 (0.5%)		0/208 (0%)		0/197 (0%)		0/208 (0%)
Small intestinal obstruction	1/197 (0.5%)		0/208 (0%)		0/197 (0%)		0/208 (0%)
Stomatitis	1/197 (0.5%)		0/208 (0%)		0/197 (0%)		0/208 (0%)
Vomiting	0/197 (0%)		3/208 (1.4%)		0/197 (0%)		0/208 (0%)
General disorders
Non-cardiac chest pain	0/197 (0%)		1/208 (0.5%)		1/197 (0.5%)		0/208 (0%)
Pyrexia	3/197 (1.5%)		6/208 (2.9%)		1/197 (0.5%)		0/208 (0%)
Asthenia	0/197 (0%)		1/208 (0.5%)		0/197 (0%)		0/208 (0%)
Chest pain	2/197 (1%)		0/208 (0%)		0/197 (0%)		0/208 (0%)
Multi-organ failure	0/197 (0%)		1/208 (0.5%)		0/197 (0%)		0/208 (0%)
Oedema peripheral	1/197 (0.5%)		1/208 (0.5%)		0/197 (0%)		0/208 (0%)
Pain	1/197 (0.5%)		1/208 (0.5%)		0/197 (0%)		0/208 (0%)
Immune system disorders
Hypersensitivity	0/197 (0%)		1/208 (0.5%)		0/197 (0%)		0/208 (0%)
Infections and infestations
Cellulitis	0/197 (0%)		1/208 (0.5%)		1/197 (0.5%)		0/208 (0%)
Incision site cellulitis	0/197 (0%)		0/208 (0%)		1/197 (0.5%)		0/208 (0%)
Breast cellulitis	1/197 (0.5%)		0/208 (0%)		0/197 (0%)		0/208 (0%)
Bronchitis	1/197 (0.5%)		2/208 (1%)		0/197 (0%)		0/208 (0%)
Clostridium difficile sepsis	1/197 (0.5%)		0/208 (0%)		0/197 (0%)		0/208 (0%)
Colonic abscess	2/197 (1%)		0/208 (0%)		0/197 (0%)		0/208 (0%)
Device related infection	1/197 (0.5%)		0/208 (0%)		0/197 (0%)		0/208 (0%)
Diverticulitis	2/197 (1%)		0/208 (0%)		0/197 (0%)		0/208 (0%)
Gastroenteritis	1/197 (0.5%)		0/208 (0%)		0/197 (0%)		0/208 (0%)
Influenza	0/197 (0%)		1/208 (0.5%)		0/197 (0%)		0/208 (0%)
Lung infection	1/197 (0.5%)		0/208 (0%)		0/197 (0%)		0/208 (0%)
Pneumonia	2/197 (1%)		3/208 (1.4%)		0/197 (0%)		0/208 (0%)
Rectal abscess	0/197 (0%)		1/208 (0.5%)		0/197 (0%)		0/208 (0%)
Sepsis	2/197 (1%)		3/208 (1.4%)		0/197 (0%)		0/208 (0%)
Septic shock	0/197 (0%)		1/208 (0.5%)		0/197 (0%)		0/208 (0%)
Urinary tract infection	0/197 (0%)		1/208 (0.5%)		0/197 (0%)		0/208 (0%)
Urosepsis	1/197 (0.5%)		0/208 (0%)		0/197 (0%)		0/208 (0%)
Wound infection	1/197 (0.5%)		0/208 (0%)		0/197 (0%)		0/208 (0%)
Investigations
Blood lactic acid increased	1/197 (0.5%)		1/208 (0.5%)		0/197 (0%)		0/208 (0%)
Body temperature increased	1/197 (0.5%)		0/208 (0%)		0/197 (0%)		0/208 (0%)
Neutrophil count decreased	0/197 (0%)		1/208 (0.5%)		0/197 (0%)		0/208 (0%)
White blood cell count increased	1/197 (0.5%)		0/208 (0%)		0/197 (0%)		0/208 (0%)
Metabolism and nutrition disorders
Dehydration	1/197 (0.5%)		2/208 (1%)		0/197 (0%)		0/208 (0%)
Hypokalaemia	1/197 (0.5%)		0/208 (0%)		0/197 (0%)		0/208 (0%)
Hypomagnesaemia	1/197 (0.5%)		0/208 (0%)		0/197 (0%)		0/208 (0%)
Hyponatraemia	1/197 (0.5%)		0/208 (0%)		0/197 (0%)		0/208 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/197 (0.5%)		0/208 (0%)		0/197 (0%)		0/208 (0%)
Back pain	1/197 (0.5%)		0/208 (0%)		0/197 (0%)		0/208 (0%)
Bone pain	1/197 (0.5%)		0/208 (0%)		0/197 (0%)		0/208 (0%)
Myalgia	0/197 (0%)		1/208 (0.5%)		0/197 (0%)		0/208 (0%)
Nervous system disorders
Headache	0/197 (0%)		1/208 (0.5%)		0/197 (0%)		0/208 (0%)
Neuropathy peripheral	1/197 (0.5%)		0/208 (0%)		0/197 (0%)		0/208 (0%)
Seizure	1/197 (0.5%)		0/208 (0%)		0/197 (0%)		0/208 (0%)
Syncope	2/197 (1%)		2/208 (1%)		0/197 (0%)		1/208 (0.5%)
Psychiatric disorders
Psychiatric decompensation	1/197 (0.5%)		0/208 (0%)		0/197 (0%)		0/208 (0%)
Mental status changes	0/197 (0%)		0/208 (0%)		0/197 (0%)		1/208 (0.5%)
Renal and urinary disorders
Acute kidney injury	0/197 (0%)		1/208 (0.5%)		0/197 (0%)		0/208 (0%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	2/197 (1%)		0/208 (0%)		1/197 (0.5%)		0/208 (0%)
Epistaxis	1/197 (0.5%)		0/208 (0%)		0/197 (0%)		0/208 (0%)
Non-cardiogenic pulmonary oedema	1/197 (0.5%)		0/208 (0%)		0/197 (0%)		0/208 (0%)
Pleural effusion	0/197 (0%)		1/208 (0.5%)		0/197 (0%)		0/208 (0%)
Pneumonitis	0/197 (0%)		2/208 (1%)		0/197 (0%)		0/208 (0%)
Pulmonary embolism	0/197 (0%)		1/208 (0.5%)		0/197 (0%)		0/208 (0%)
Respiratory failure	0/197 (0%)		1/208 (0.5%)		0/197 (0%)		0/208 (0%)
Skin and subcutaneous tissue disorders
Drug eruption	1/197 (0.5%)		0/208 (0%)		0/197 (0%)		0/208 (0%)
Hypersensitivity vasculitis	0/197 (0%)		1/208 (0.5%)		0/197 (0%)		0/208 (0%)
Rash generalised	0/197 (0%)		1/208 (0.5%)		0/197 (0%)		0/208 (0%)
Vascular disorders
Arteriosclerosis	0/197 (0%)		1/208 (0.5%)		0/197 (0%)		0/208 (0%)
Deep vein thrombosis	1/197 (0.5%)		1/208 (0.5%)		0/197 (0%)		0/208 (0%)
Hypertension	0/197 (0%)		1/208 (0.5%)		0/197 (0%)		0/208 (0%)
Hypotension	0/197 (0%)		1/208 (0.5%)		0/197 (0%)		0/208 (0%)
Embolism	0/197 (0%)		0/208 (0%)		1/197 (0.5%)		0/208 (0%)
Other (Not Including Serious) Adverse Events
	Arm 1: SPI-2012 and TC -Treatment Period		Arm 2: Pegfilgrastim and TC -Treatment Period		Arm 1: SPI-2012 and TC - Follow up Period		Arm 2: Pegfilgrastim and TC - Follow up Period
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	192/197 (97.5%)		203/208 (97.6%)		92/197 (46.7%)		82/208 (39.4%)
Blood and lymphatic system disorders
Neutropenia	67/197 (34%)		65/208 (31.3%)		1/197 (0.5%)		1/208 (0.5%)
Anaemia	51/197 (25.9%)		39/208 (18.8%)		3/197 (1.5%)		0/208 (0%)
Lymphopenia	19/197 (9.6%)		22/208 (10.6%)		0/197 (0%)		0/208 (0%)
Leukopenia	13/197 (6.6%)		14/208 (6.7%)		1/197 (0.5%)		1/208 (0.5%)
Thrombocytopenia	9/197 (4.6%)		5/208 (2.4%)		0/197 (0%)		0/208 (0%)
Cardiac disorders
Tachycardia	11/197 (5.6%)		10/208 (4.8%)		1/197 (0.5%)		0/208 (0%)
Eye disorders
Lacrimation increased	9/197 (4.6%)		9/208 (4.3%)		0/197 (0%)		0/208 (0%)
Gastrointestinal disorders
Nausea	112/197 (56.9%)		104/208 (50%)		11/197 (5.6%)		7/208 (3.4%)
Diarrhoea	87/197 (44.2%)		86/208 (41.3%)		3/197 (1.5%)		3/208 (1.4%)
Constipation	62/197 (31.5%)		48/208 (23.1%)		2/197 (1%)		2/208 (1%)
Vomiting	40/197 (20.3%)		34/208 (16.3%)		4/197 (2%)		2/208 (1%)
Stomatitis	26/197 (13.2%)		25/208 (12%)		3/197 (1.5%)		2/208 (1%)
Dyspepsia	20/197 (10.2%)		25/208 (12%)		0/197 (0%)		2/208 (1%)
Abdominal pain	20/197 (10.2%)		17/208 (8.2%)		5/197 (2.5%)		2/208 (1%)
Abdominal pain upper	11/197 (5.6%)		15/208 (7.2%)		1/197 (0.5%)		0/208 (0%)
Dry mouth	13/197 (6.6%)		12/208 (5.8%)		0/197 (0%)		3/208 (1.4%)
Gastrooesophageal reflux disease	12/197 (6.1%)		13/208 (6.3%)		1/197 (0.5%)		1/208 (0.5%)
General disorders
Fatigue	120/197 (60.9%)		124/208 (59.6%)		14/197 (7.1%)		8/208 (3.8%)
Pyrexia	45/197 (22.8%)		45/208 (21.6%)		0/197 (0%)		1/208 (0.5%)
Oedema peripheral	36/197 (18.3%)		28/208 (13.5%)		3/197 (1.5%)		3/208 (1.4%)
Pain	31/197 (15.7%)		30/208 (14.4%)		1/197 (0.5%)		0/208 (0%)
Asthenia	16/197 (8.1%)		18/208 (8.7%)		1/197 (0.5%)		0/208 (0%)
Mucosal inflammation	14/197 (7.1%)		10/208 (4.8%)		0/197 (0%)		0/208 (0%)
Chills	11/197 (5.6%)		9/208 (4.3%)		1/197 (0.5%)		0/208 (0%)
Infections and infestations
Urinary tract infection	19/197 (9.6%)		23/208 (11.1%)		3/197 (1.5%)		3/208 (1.4%)
Injury, poisoning and procedural complications
Radiation skin injury	0/197 (0%)		4/208 (1.9%)		10/197 (5.1%)		7/208 (3.4%)
Investigations
Lymphocyte count decreased	80/197 (40.6%)		74/208 (35.6%)		2/197 (1%)		0/208 (0%)
White blood cell count decreased	48/197 (24.4%)		43/208 (20.7%)		1/197 (0.5%)		0/208 (0%)
Neutrophil count decreased	35/197 (17.8%)		38/208 (18.3%)		0/197 (0%)		0/208 (0%)
White blood cell count increased	29/197 (14.7%)		20/208 (9.6%)		0/197 (0%)		0/208 (0%)
Platelet count decreased	19/197 (9.6%)		9/208 (4.3%)		0/197 (0%)		0/208 (0%)
Neutrophil count increased	13/197 (6.6%)		11/208 (5.3%)		0/197 (0%)		0/208 (0%)
Metabolism and nutrition disorders
Decreased appetite	38/197 (19.3%)		31/208 (14.9%)		0/197 (0%)		4/208 (1.9%)
Dehydration	22/197 (11.2%)		21/208 (10.1%)		0/197 (0%)		0/208 (0%)
Hypokalaemia	22/197 (11.2%)		13/208 (6.3%)		0/197 (0%)		1/208 (0.5%)
Musculoskeletal and connective tissue disorders
Bone pain	71/197 (36%)		70/208 (33.7%)		6/197 (3%)		5/208 (2.4%)
Arthralgia	48/197 (24.4%)		36/208 (17.3%)		20/197 (10.2%)		11/208 (5.3%)
Back pain	41/197 (20.8%)		40/208 (19.2%)		4/197 (2%)		8/208 (3.8%)
Myalgia	43/197 (21.8%)		26/208 (12.5%)		3/197 (1.5%)		2/208 (1%)
Pain in extremity	22/197 (11.2%)		31/208 (14.9%)		8/197 (4.1%)		7/208 (3.4%)
Muscle spasms	12/197 (6.1%)		8/208 (3.8%)		0/197 (0%)		1/208 (0.5%)
Muscular weakness	6/197 (3%)		11/208 (5.3%)		4/197 (2%)		2/208 (1%)
Nervous system disorders
Headache	59/197 (29.9%)		55/208 (26.4%)		5/197 (2.5%)		5/208 (2.4%)
Dysgeusia	36/197 (18.3%)		29/208 (13.9%)		0/197 (0%)		0/208 (0%)
Dizziness	37/197 (18.8%)		23/208 (11.1%)		7/197 (3.6%)		2/208 (1%)
Neuropathy peripheral	15/197 (7.6%)		24/208 (11.5%)		9/197 (4.6%)		4/208 (1.9%)
Reproductive system and breast disorders
Breast pain	1/197 (0.5%)		10/208 (4.8%)		9/197 (4.6%)		5/208 (2.4%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	38/197 (19.3%)		26/208 (12.5%)		3/197 (1.5%)		2/208 (1%)
Cough	32/197 (16.2%)		31/208 (14.9%)		7/197 (3.6%)		7/208 (3.4%)
Oropharyngeal pain	21/197 (10.7%)		25/208 (12%)		1/197 (0.5%)		3/208 (1.4%)
Epistaxis	10/197 (5.1%)		18/208 (8.7%)		1/197 (0.5%)		0/208 (0%)
Nasal congestion	10/197 (5.1%)		4/208 (1.9%)		0/197 (0%)		3/208 (1.4%)
Skin and subcutaneous tissue disorders
Alopecia	95/197 (48.2%)		93/208 (44.7%)		2/197 (1%)		1/208 (0.5%)
Rash	32/197 (16.2%)		44/208 (21.2%)		3/197 (1.5%)		1/208 (0.5%)
Pruritus	20/197 (10.2%)		19/208 (9.1%)		2/197 (1%)		1/208 (0.5%)
Nail discolouration	11/197 (5.6%)		19/208 (9.1%)		0/197 (0%)		0/208 (0%)
Erythema	8/197 (4.1%)		14/208 (6.7%)		4/197 (2%)		5/208 (2.4%)
Urticaria	9/197 (4.6%)		13/208 (6.3%)		0/197 (0%)		0/208 (0%)
Dry skin	10/197 (5.1%)		11/208 (5.3%)		0/197 (0%)		0/208 (0%)
Vascular disorders
Hot flush	21/197 (10.7%)		22/208 (10.6%)		15/197 (7.6%)		16/208 (7.7%)

Limitations/Caveats

[Not Specified]

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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.