Trial Outcomes & Findings for Demonstrate Efficacy and Safety of Metastatic Breast Cancer (NCT NCT01084876)

NCT ID: NCT01084876

Last Updated: 2025-02-11

Results Overview

Best Overall Response (BOR) was derived from the overall response across all time points until after Cycle 8 using Independent Tumor Review Committee (ITRC) data in the FAS. Objective Response Rate (ORR) was defined as the number of patients with a BOR of complete response (CR) or partial response (PR) divided by the number of patients in the corresponding population, as assessed by Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 475 participants
• Primary outcome timeframe: 6 months (up to 24 weeks)
• Results posted on: 2025-02-11

Participant Flow

A total of 475 patients initiated Main Study Treatment Period and were included in the Full Analysis Set (FAS).

Participant milestones

Measure	CT-P6 CT-P6 was administered at a loading dose of 8 mg/kg body weight by intravenous (IV) infusion over 90 minutes on Day 1, Cycle 1, then at 6 mg/kg repeated at 3-weekly intervals until disease progression, death or discontinuation. Paclitaxel was administered at a dose of 175 mg/m2 body surface area (BSA) as a continuous 3-hour IV infusion on the day following the first dose of study drug (CT-P6). If the first dose of study drug was well tolerated, subsequent doses of paclitaxel were given immediately after the next dose of study drug. Paclitaxel cycles were repeated every 3 weeks until disease progression, death or discontinuation.	Herceptin Herceptin was administered at a loading dose of 8 mg/kg body weight by IV infusion over 90 minutes on Day 1, Cycle 1, then at 6 mg/kg repeated at 3-weekly intervals until disease progression, death or discontinuation. Paclitaxel was administered at a dose of 175 mg/m2 BSA as a continuous 3-hour IV infusion on the day following the first dose of study drug (Herceptin). If the first dose of study drug was well tolerated, subsequent doses of paclitaxel were given immediately after the next dose of study drug. Paclitaxel cycles were repeated every 3 weeks until disease progression, death or discontinuation.
Main Study Treatment Period STARTED	244	231
Main Study Treatment Period COMPLETED	185	192
Main Study Treatment Period NOT COMPLETED	59	39
Treatment Period Beyond Cycle 8 STARTED	168	168
Treatment Period Beyond Cycle 8 COMPLETED	0	0
Treatment Period Beyond Cycle 8 NOT COMPLETED	168	168

Reasons for withdrawal

Measure	CT-P6 CT-P6 was administered at a loading dose of 8 mg/kg body weight by intravenous (IV) infusion over 90 minutes on Day 1, Cycle 1, then at 6 mg/kg repeated at 3-weekly intervals until disease progression, death or discontinuation. Paclitaxel was administered at a dose of 175 mg/m2 body surface area (BSA) as a continuous 3-hour IV infusion on the day following the first dose of study drug (CT-P6). If the first dose of study drug was well tolerated, subsequent doses of paclitaxel were given immediately after the next dose of study drug. Paclitaxel cycles were repeated every 3 weeks until disease progression, death or discontinuation.	Herceptin Herceptin was administered at a loading dose of 8 mg/kg body weight by IV infusion over 90 minutes on Day 1, Cycle 1, then at 6 mg/kg repeated at 3-weekly intervals until disease progression, death or discontinuation. Paclitaxel was administered at a dose of 175 mg/m2 BSA as a continuous 3-hour IV infusion on the day following the first dose of study drug (Herceptin). If the first dose of study drug was well tolerated, subsequent doses of paclitaxel were given immediately after the next dose of study drug. Paclitaxel cycles were repeated every 3 weeks until disease progression, death or discontinuation.
Main Study Treatment Period Adverse Event	12	7
Main Study Treatment Period Disease Progression	41	24
Main Study Treatment Period Physician Decision	2	0
Main Study Treatment Period Withdrawal by Subject	4	6
Main Study Treatment Period Other Reason	0	1
Main Study Treatment Period Other	0	1
Treatment Period Beyond Cycle 8 Adverse Event	8	2
Treatment Period Beyond Cycle 8 Disease Progression	129	119
Treatment Period Beyond Cycle 8 Physician Decision	6	5
Treatment Period Beyond Cycle 8 Withdrawal by Subject	12	20
Treatment Period Beyond Cycle 8 Other Reason	7	13
Treatment Period Beyond Cycle 8 Other	6	9

Baseline Characteristics

Demonstrate Efficacy and Safety of Metastatic Breast Cancer

Baseline characteristics by cohort

Measure	CT-P6 n=244 Participants CT-P6: 8 mg/kg for loading or 6 mg/kg for maintenance dose via IV infusion every 3 weeks. Paclitaxel: 175 mg/m2 BSA via IV infusion on the day following the first dose of study drug (CT-P6). Paclitaxel cycles were repeated every 3 weeks.	Herceptin n=231 Participants Herceptin: 8 mg/kg for loading or 6 mg/kg for maintenance dose via IV infusion every 3 weeks. Paclitaxel: 175 mg/m2 BSA via IV infusion on the day following the first dose of study drug (Herceptin). Paclitaxel cycles were repeated every 3 weeks.	Total n=475 Participants Total of all reporting groups
Age, Continuous	53.8 years STANDARD_DEVIATION 9.70 • n=5 Participants	51.9 years STANDARD_DEVIATION 10.75 • n=7 Participants	52.9 years STANDARD_DEVIATION 10.26 • n=5 Participants
Age, Customized >=65 years	34 Participants n=5 Participants	22 Participants n=7 Participants	56 Participants n=5 Participants
Age, Customized <65 years	210 Participants n=5 Participants	209 Participants n=7 Participants	419 Participants n=5 Participants
Sex: Female, Male Female	244 Participants n=5 Participants	231 Participants n=7 Participants	475 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized White	158 Participants n=5 Participants	141 Participants n=7 Participants	299 Participants n=5 Participants
Race/Ethnicity, Customized Asian	86 Participants n=5 Participants	90 Participants n=7 Participants	176 Participants n=5 Participants
Region of Enrollment Belarus	8 Participants n=5 Participants	8 Participants n=7 Participants	16 Participants n=5 Participants
Region of Enrollment Bulgaria	13 Participants n=5 Participants	7 Participants n=7 Participants	20 Participants n=5 Participants
Region of Enrollment Georgia	10 Participants n=5 Participants	11 Participants n=7 Participants	21 Participants n=5 Participants
Region of Enrollment Hong Kong	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Region of Enrollment India	31 Participants n=5 Participants	35 Participants n=7 Participants	66 Participants n=5 Participants
Region of Enrollment South Korea	31 Participants n=5 Participants	32 Participants n=7 Participants	63 Participants n=5 Participants
Region of Enrollment Latvia	7 Participants n=5 Participants	6 Participants n=7 Participants	13 Participants n=5 Participants
Region of Enrollment Malaysia	2 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants
Region of Enrollment Philippines	17 Participants n=5 Participants	15 Participants n=7 Participants	32 Participants n=5 Participants
Region of Enrollment Poland	4 Participants n=5 Participants	4 Participants n=7 Participants	8 Participants n=5 Participants
Region of Enrollment Romania	6 Participants n=5 Participants	7 Participants n=7 Participants	13 Participants n=5 Participants
Region of Enrollment Russia	47 Participants n=5 Participants	39 Participants n=7 Participants	86 Participants n=5 Participants
Region of Enrollment Serbia	4 Participants n=5 Participants	5 Participants n=7 Participants	9 Participants n=5 Participants
Region of Enrollment Singapore	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment Thailand	4 Participants n=5 Participants	3 Participants n=7 Participants	7 Participants n=5 Participants
Region of Enrollment Turkey	4 Participants n=5 Participants	2 Participants n=7 Participants	6 Participants n=5 Participants
Region of Enrollment Ukraine	55 Participants n=5 Participants	52 Participants n=7 Participants	107 Participants n=5 Participants
Childbearing Potential Yes	53 Participants n=5 Participants	74 Participants n=7 Participants	127 Participants n=5 Participants
Childbearing Potential No	191 Participants n=5 Participants	157 Participants n=7 Participants	348 Participants n=5 Participants
Height at Screening	159.5 cm STANDARD_DEVIATION 6.98 • n=5 Participants	158.9 cm STANDARD_DEVIATION 7.21 • n=7 Participants	159.2 cm STANDARD_DEVIATION 7.09 • n=5 Participants
Weight at Screening	67.5 kg STANDARD_DEVIATION 14.85 • n=5 Participants	69.3 kg STANDARD_DEVIATION 16.06 • n=7 Participants	68.4 kg STANDARD_DEVIATION 15.46 • n=5 Participants
BSA at Screening	1.72 m2 STANDARD_DEVIATION 0.203 • n=5 Participants	1.74 m2 STANDARD_DEVIATION 0.220 • n=7 Participants	1.73 m2 STANDARD_DEVIATION 0.212 • n=5 Participants
Prior Chemotherapy Yes	107 Participants n=5 Participants	100 Participants n=7 Participants	207 Participants n=5 Participants
Prior Chemotherapy No	137 Participants n=5 Participants	131 Participants n=7 Participants	268 Participants n=5 Participants
ECOG performance status Grade 0	128 Participants n=5 Participants	116 Participants n=7 Participants	244 Participants n=5 Participants
ECOG performance status Grade 1	115 Participants n=5 Participants	115 Participants n=7 Participants	230 Participants n=5 Participants
ECOG performance status Grade 2	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Karnofsky performance status Category 1	236 Participants n=5 Participants	217 Participants n=7 Participants	453 Participants n=5 Participants
Karnofsky performance status Category 2	4 Participants n=5 Participants	7 Participants n=7 Participants	11 Participants n=5 Participants
Karnofsky performance status Not reported	4 Participants n=5 Participants	7 Participants n=7 Participants	11 Participants n=5 Participants

PRIMARY outcome

Timeframe: 6 months (up to 24 weeks)

Population: Full Analysis Set - consisted of all randomized patients who received any study drug and had at least one post-baseline assessment, with the exception of the patients who violated against Herceptin indication. All outcome measures of the Phase 3 study (CT-P6 3.1) were analyzed in conjunction with those of the Phase 1/2b study (CT-P6 1.1).

Best Overall Response (BOR) was derived from the overall response across all time points until after Cycle 8 using Independent Tumor Review Committee (ITRC) data in the FAS. Objective Response Rate (ORR) was defined as the number of patients with a BOR of complete response (CR) or partial response (PR) divided by the number of patients in the corresponding population, as assessed by Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1.

Outcome measures

Measure	CT-P6 n=244 Participants The ORR results for CT-P6 treatment group based on BOR during the Main Study Treatment Period (up to Cycle 8; 6 months) from the ITRC are presented below.	Herceptin n=231 Participants The ORR results for Herceptin treatment group based on BOR during the Main Study Treatment Period from the ITRC are presented below.
Objective Response Rate	138 Participants	143 Participants

SECONDARY outcome

Timeframe: Through study completion, approximately 40 months

Population: Full Analysis Set (FAS) - consisted of all randomized patients who received any study drug and had at least one post-baseline assessment, with the exception of the patients who violated against Herceptin indication. All outcome measures of the Phase 3 study (CT-P6 3.1) were analyzed in conjunction with those of the Phase 1/2b study (CT-P6 1.1).

Time from randomization to determined progressive disease, as assessed by RECIST version 1.1.

Outcome measures

Measure	CT-P6 n=244 Participants The ORR results for CT-P6 treatment group based on BOR during the Main Study Treatment Period (up to Cycle 8; 6 months) from the ITRC are presented below.	Herceptin n=231 Participants The ORR results for Herceptin treatment group based on BOR during the Main Study Treatment Period from the ITRC are presented below.
Time to Progression ITRC	11.07 months Interval 9.69 to 12.42	12.52 months Interval 11.1 to Not estimable due to insufficient number of event.
Time to Progression Investigator	10.99 months Interval 9.7 to 11.71	11.25 months Interval 9.74 to 12.47

SECONDARY outcome

Timeframe: Through study completion, approximately 40 months

Population: Full Analysis Set (FAS) - consisted of all randomized patients who received any study drug and had at least one post-baseline assessment, with the exception of the patients who violated against Herceptin indication. All outcome measures of the Phase 3 study (CT-P6 3.1) were analyzed in conjunction with those of the Phase 1/2b study (CT-P6 1.1).

Time from randomization to observed tumor response (Complete Response or Partial Response), as assessed by RECIST 1.1

Outcome measures

Measure	CT-P6 n=244 Participants The ORR results for CT-P6 treatment group based on BOR during the Main Study Treatment Period (up to Cycle 8; 6 months) from the ITRC are presented below.	Herceptin n=231 Participants The ORR results for Herceptin treatment group based on BOR during the Main Study Treatment Period from the ITRC are presented below.
Time to Response ITRC	1.38 months Interval 1.38 to 1.41	1.38 months Interval 1.38 to 1.41
Time to Response Investigator	1.41 months Interval 1.41 to 1.45	1.41 months Interval 1.38 to 1.45

SECONDARY outcome

Timeframe: Through study completion, approximately 40 months

Population: Full Analysis Set (FAS) - consisted of all randomized patients who received any study drug and had at least one post-baseline assessment, with the exception of the patients who violated against Herceptin indication. All outcome measures of the Phase 3 study (CT-P6 3.1) were analyzed in conjunction with those of the Phase 1/2b study (CT-P6 1.1).

Time from randomization to radiological progression or death from any cause, as assessed by RECIST 1.1

Outcome measures

Measure	CT-P6 n=244 Participants The ORR results for CT-P6 treatment group based on BOR during the Main Study Treatment Period (up to Cycle 8; 6 months) from the ITRC are presented below.	Herceptin n=231 Participants The ORR results for Herceptin treatment group based on BOR during the Main Study Treatment Period from the ITRC are presented below.
Progression Free Survival	10.99 months Interval 9.67 to 11.58	11.15 months Interval 9.74 to 12.43

SECONDARY outcome

Timeframe: Through study completion, approximately 40 months

Population: Full Analysis Set (FAS) - consisted of all randomized patients who received any study drug and had at least one post-baseline assessment, with the exception of the patients who violated against Herceptin indication. All outcome measures of the Phase 3 study (CT-P6 3.1) were analyzed in conjunction with those of the Phase 1/2b study (CT-P6 1.1).

The number of days between the date of randomization and the date of death from any cause.

Outcome measures

Measure	CT-P6 n=244 Participants The ORR results for CT-P6 treatment group based on BOR during the Main Study Treatment Period (up to Cycle 8; 6 months) from the ITRC are presented below.	Herceptin n=231 Participants The ORR results for Herceptin treatment group based on BOR during the Main Study Treatment Period from the ITRC are presented below.
Overall Survival	28.82 months Interval 25.1 to 32.96	26.84 months Interval 22.43 to 32.5

SECONDARY outcome

Timeframe: Through study completion, approximately 40 months

Population: Safety Analysis Set (SAF) - consisted of all patients in the FAS, analyzed as treated. All patients who received at least one dose of CT-P6 were analyzed under the CT-P6 treatment group. All other patients were analyzed under the Herceptin treatment group. All outcome measures of the Phase 3 study (CT-P6 3.1) were analyzed in conjunction with those of the Phase 1/2b study (CT-P6 1.1).

Mean change from baseline to endpoint assessment in left ventricular ejection fraction (LVEF) (%)

Outcome measures

Measure	CT-P6 n=185 Participants The ORR results for CT-P6 treatment group based on BOR during the Main Study Treatment Period (up to Cycle 8; 6 months) from the ITRC are presented below.	Herceptin n=173 Participants The ORR results for Herceptin treatment group based on BOR during the Main Study Treatment Period from the ITRC are presented below.
Safety Endpoints; Cardiotoxicity	-4.56 %; percent change in LVEF Standard Deviation 6.56	-4.98 %; percent change in LVEF Standard Deviation 6.54

SECONDARY outcome

Timeframe: During treatment, median of 13 cycles (every cycle is 3 weeks)

Population: Safety Analysis Set (SAF) - consisted of all patients in the FAS, analyzed as treated. All patients who received at least one dose of CT-P6 were analyzed under the CT-P6 treatment group. All other patients were analyzed under the Herceptin treatment group. All outcome measures of the Phase 3 study (CT-P6 3.1) were analyzed in conjunction with those of the Phase 1/2b study (CT-P6 1.1).

Assessed by the proportion of patients with development of antibodies to study drug (positive anti-drug antibody [ADA] results after the first study drug infusion)

Outcome measures

Measure	CT-P6 n=244 Participants The ORR results for CT-P6 treatment group based on BOR during the Main Study Treatment Period (up to Cycle 8; 6 months) from the ITRC are presented below.	Herceptin n=231 Participants The ORR results for Herceptin treatment group based on BOR during the Main Study Treatment Period from the ITRC are presented below.
Safety Endpoints; Immunogenicity ADA positive patients with at least 1 result at any time during the study	4 Participants	2 Participants
Safety Endpoints; Immunogenicity ADA positive patients with a result at baseline visit	1 Participants	2 Participants
Safety Endpoints; Immunogenicity ADA positive patients with at least 1 result after the first infusion	3 Participants	0 Participants

SECONDARY outcome

Timeframe: predose and at 1.5 hours (end of infusion) of each cycle

Population: PK Analysis Set (PKAS) - consisted of all FAS patients who had achieved steady state by the 8th cycle, which required 3 consecutive similar trough concentrations. All outcome measures of the Phase 3 study (CT-P6 3.1) were analyzed in conjunction with those of the Phase 1/2b study (CT-P6 1.1).

Trough concentration at steady state

Outcome measures

Measure	CT-P6 n=150 Participants The ORR results for CT-P6 treatment group based on BOR during the Main Study Treatment Period (up to Cycle 8; 6 months) from the ITRC are presented below.	Herceptin n=160 Participants The ORR results for Herceptin treatment group based on BOR during the Main Study Treatment Period from the ITRC are presented below.
Pharmacokinetic Endpoints; Ctroughss	23.6 ug/mL Standard Deviation 24.5	24.2 ug/mL Standard Deviation 27.8

Adverse Events

CT-P6

Serious events: 34 serious events

Other events: 227 other events

Deaths: 8 deaths

Herceptin

Serious events: 39 serious events

Other events: 214 other events

Deaths: 8 deaths

Serious adverse events

Measure	CT-P6 n=244 participants at risk CT-P6: 8 mg/kg for loading or 6 mg/kg for maintenance dose via IV infusion every 3 weeks. Paclitaxel: 175 mg/m2 BSA via IV infusion on the day following the first dose of study drug (CT-P6). Paclitaxel cycles were repeated every 3 weeks.	Herceptin n=231 participants at risk Herceptin: 8 mg/kg for loading or 6 mg/kg for maintenance dose via IV infusion every 3 weeks. Paclitaxel: 175 mg/m2 BSA via IV infusion on the day following the first dose of study drug (Herceptin). Paclitaxel cycles were repeated every 3 weeks.
Blood and lymphatic system disorders Anaemia	0.41% 1/244 • Number of events 1 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.	0.87% 2/231 • Number of events 2 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.
Blood and lymphatic system disorders Febrile neutropenia	2.0% 5/244 • Number of events 5 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.	1.7% 4/231 • Number of events 4 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.
Blood and lymphatic system disorders Neutropenia	0.82% 2/244 • Number of events 2 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.	2.6% 6/231 • Number of events 6 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.
Blood and lymphatic system disorders Thrombocytopenia	0.41% 1/244 • Number of events 1 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.	0.00% 0/231 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.
Cardiac disorders Cardiac arrest	0.41% 1/244 • Number of events 1 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.	0.00% 0/231 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.
Cardiac disorders Cardiac failure acute	0.00% 0/244 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.	0.43% 1/231 • Number of events 1 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.
Cardiac disorders Cardiac failure congestive	0.41% 1/244 • Number of events 1 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.	0.00% 0/231 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.
Cardiac disorders Left ventricular dysfunction	0.82% 2/244 • Number of events 3 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.	0.00% 0/231 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.
Gastrointestinal disorders Abdominal pain	0.41% 1/244 • Number of events 1 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.	0.00% 0/231 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.
Gastrointestinal disorders Colitis	0.00% 0/244 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.	0.43% 1/231 • Number of events 1 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.
Gastrointestinal disorders Diarrhoea	0.41% 1/244 • Number of events 1 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.	0.00% 0/231 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.
Gastrointestinal disorders Nausea	0.41% 1/244 • Number of events 1 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.	0.00% 0/231 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.
Gastrointestinal disorders Vomiting	0.41% 1/244 • Number of events 1 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.	0.43% 1/231 • Number of events 1 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.
General disorders Death	0.00% 0/244 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.	0.87% 2/231 • Number of events 2 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.
General disorders Disease progression	1.6% 4/244 • Number of events 4 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.	2.6% 6/231 • Number of events 6 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.
General disorders Inflammation	0.41% 1/244 • Number of events 1 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.	0.00% 0/231 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.
General disorders Infusion related reaction	0.82% 2/244 • Number of events 2 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.	0.43% 1/231 • Number of events 1 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.
General disorders Pyrexia	0.82% 2/244 • Number of events 2 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.	0.43% 1/231 • Number of events 2 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.
Hepatobiliary disorders Cholangitis	0.00% 0/244 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.	0.43% 1/231 • Number of events 3 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.
Hepatobiliary disorders Cholecystitis acute	0.00% 0/244 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.	0.43% 1/231 • Number of events 1 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.
Hepatobiliary disorders Hepatitis cholestatic	0.00% 0/244 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.	0.43% 1/231 • Number of events 1 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.
Immune system disorders Hypersensitivity	0.82% 2/244 • Number of events 3 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.	0.00% 0/231 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.
Infections and infestations Acute tonsillitis	0.41% 1/244 • Number of events 1 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.	0.00% 0/231 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.
Infections and infestations Bacteraemia	0.82% 2/244 • Number of events 2 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.	0.00% 0/231 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.
Infections and infestations Gangrene	0.41% 1/244 • Number of events 1 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.	0.00% 0/231 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.
Infections and infestations Gastroenteritis	0.00% 0/244 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.	0.43% 1/231 • Number of events 1 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.
Infections and infestations Herpes zoster	0.00% 0/244 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.	0.43% 1/231 • Number of events 1 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.
Infections and infestations Malaria	0.00% 0/244 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.	0.43% 1/231 • Number of events 1 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.
Infections and infestations Neutropenic infection	0.00% 0/244 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.	0.43% 1/231 • Number of events 1 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.
Infections and infestations Pneumonia	0.82% 2/244 • Number of events 2 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.	1.3% 3/231 • Number of events 3 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.
Infections and infestations Sepsis	0.00% 0/244 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.	0.43% 1/231 • Number of events 1 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.
Infections and infestations Urinary tract infection	0.41% 1/244 • Number of events 1 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.	0.87% 2/231 • Number of events 2 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.
Injury, poisoning and procedural complications Concussion	0.41% 1/244 • Number of events 1 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.	0.00% 0/231 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.
Injury, poisoning and procedural complications Femur fracture	0.41% 1/244 • Number of events 1 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.	0.00% 0/231 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.
Injury, poisoning and procedural complications Radius fracture	0.00% 0/244 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.	0.43% 1/231 • Number of events 1 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.
Injury, poisoning and procedural complications Spinal fracture	0.00% 0/244 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.	0.43% 1/231 • Number of events 1 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.
Investigations Endoscopic retrograde cholangiopancreatography	0.00% 0/244 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.	0.43% 1/231 • Number of events 1 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.
Investigations Hepatic enzyme increased	0.41% 1/244 • Number of events 1 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.	0.00% 0/231 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.
Metabolism and nutrition disorders Hypercalcaemia	0.00% 0/244 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.	0.43% 1/231 • Number of events 1 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.
Metabolism and nutrition disorders Hypoglycaemia	0.00% 0/244 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.	0.43% 1/231 • Number of events 1 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/244 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.	0.43% 1/231 • Number of events 1 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant neoplasm progression	0.41% 1/244 • Number of events 1 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.	0.00% 0/231 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant pleural effusion	0.41% 1/244 • Number of events 1 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.	0.00% 0/231 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to central nervous system	0.00% 0/244 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.	1.3% 3/231 • Number of events 3 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.
Nervous system disorders Brain oedema	0.00% 0/244 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.	0.43% 1/231 • Number of events 1 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.
Nervous system disorders Cerebrovascular accident	0.41% 1/244 • Number of events 1 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.	0.00% 0/231 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.
Nervous system disorders Neuropathy peripheral	0.00% 0/244 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.	0.43% 1/231 • Number of events 1 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.
Reproductive system and breast disorders Metrorrhagia	0.00% 0/244 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.	0.43% 1/231 • Number of events 1 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.
Reproductive system and breast disorders Vulval ulceration	0.00% 0/244 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.	0.43% 1/231 • Number of events 1 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.41% 1/244 • Number of events 1 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.	0.00% 0/231 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.
Respiratory, thoracic and mediastinal disorders Interstitial lung disease	0.41% 1/244 • Number of events 1 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.	0.00% 0/231 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/244 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.	0.43% 1/231 • Number of events 1 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.41% 1/244 • Number of events 1 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.	0.00% 0/231 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.
Skin and subcutaneous tissue disorders Leukocytoclastic vasculitis	0.41% 1/244 • Number of events 1 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.	0.00% 0/231 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.
Surgical and medical procedures Biliary drainage	0.00% 0/244 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.	0.43% 1/231 • Number of events 4 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.
Surgical and medical procedures Cataract operation	0.41% 1/244 • Number of events 1 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.	0.00% 0/231 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.
Surgical and medical procedures Extended radical mastectomy	0.00% 0/244 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.	0.43% 1/231 • Number of events 1 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.
Surgical and medical procedures Mastectomy	0.41% 1/244 • Number of events 1 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.	0.00% 0/231 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.
Vascular disorders Hypertension	0.00% 0/244 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.	0.43% 1/231 • Number of events 1 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.

Other adverse events

Measure	CT-P6 n=244 participants at risk CT-P6: 8 mg/kg for loading or 6 mg/kg for maintenance dose via IV infusion every 3 weeks. Paclitaxel: 175 mg/m2 BSA via IV infusion on the day following the first dose of study drug (CT-P6). Paclitaxel cycles were repeated every 3 weeks.	Herceptin n=231 participants at risk Herceptin: 8 mg/kg for loading or 6 mg/kg for maintenance dose via IV infusion every 3 weeks. Paclitaxel: 175 mg/m2 BSA via IV infusion on the day following the first dose of study drug (Herceptin). Paclitaxel cycles were repeated every 3 weeks.
Blood and lymphatic system disorders Neutropenia	27.9% 68/244 • Number of events 126 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.	32.9% 76/231 • Number of events 156 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.
Gastrointestinal disorders Abdominal pain	5.7% 14/244 • Number of events 20 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.	5.6% 13/231 • Number of events 14 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.
Gastrointestinal disorders Constipation	4.1% 10/244 • Number of events 14 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.	7.8% 18/231 • Number of events 22 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.
Gastrointestinal disorders Diarrhoea	13.9% 34/244 • Number of events 52 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.	19.0% 44/231 • Number of events 74 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.
Gastrointestinal disorders Nausea	16.8% 41/244 • Number of events 152 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.	17.3% 40/231 • Number of events 75 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.
Metabolism and nutrition disorders Hypercholesterolaemia	3.3% 8/244 • Number of events 23 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.	6.5% 15/231 • Number of events 25 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.
Gastrointestinal disorders Stomatitis	5.7% 14/244 • Number of events 25 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.	7.4% 17/231 • Number of events 20 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.
Gastrointestinal disorders Vomiting	9.4% 23/244 • Number of events 34 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.	11.7% 27/231 • Number of events 37 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.
General disorders Asthenia	20.5% 50/244 • Number of events 132 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.	14.7% 34/231 • Number of events 52 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.
General disorders Chills	4.1% 10/244 • Number of events 15 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.	8.2% 19/231 • Number of events 20 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.
General disorders Fatigue	12.3% 30/244 • Number of events 78 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.	14.7% 34/231 • Number of events 64 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.
General disorders Oedema peripheral	4.1% 10/244 • Number of events 13 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.	5.6% 13/231 • Number of events 18 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.
General disorders Pain	4.5% 11/244 • Number of events 17 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.	6.9% 16/231 • Number of events 31 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.
General disorders Pyrexia	9.4% 23/244 • Number of events 40 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.	12.1% 28/231 • Number of events 44 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.
Infections and infestations Upper respiratory tract infection	3.3% 8/244 • Number of events 12 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.	6.1% 14/231 • Number of events 19 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.
Investigations Alanine aminotransferase increased	9.4% 23/244 • Number of events 51 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.	10.4% 24/231 • Number of events 54 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.
Investigations Aspartate aminotransferase increased	7.0% 17/244 • Number of events 28 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.	6.5% 15/231 • Number of events 28 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.
Investigations Blood alkaline phosphatase increased	5.3% 13/244 • Number of events 18 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.	4.8% 11/231 • Number of events 19 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.
Investigations Gamma-glutamyltransferase increased	7.4% 18/244 • Number of events 39 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.	5.2% 12/231 • Number of events 27 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.
Metabolism and nutrition disorders Decreased appetite	7.8% 19/244 • Number of events 37 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.	6.9% 16/231 • Number of events 30 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.
Blood and lymphatic system disorders Anaemia	12.7% 31/244 • Number of events 58 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.	16.5% 38/231 • Number of events 67 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.
Blood and lymphatic system disorders Leukopenia	11.5% 28/244 • Number of events 40 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.	21.6% 50/231 • Number of events 85 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.
Musculoskeletal and connective tissue disorders Arthralgia	9.0% 22/244 • Number of events 82 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.	14.3% 33/231 • Number of events 125 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.
Musculoskeletal and connective tissue disorders Back pain	6.1% 15/244 • Number of events 20 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.	8.7% 20/231 • Number of events 30 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.
Musculoskeletal and connective tissue disorders Bone pain	9.8% 24/244 • Number of events 63 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.	7.4% 17/231 • Number of events 30 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	3.7% 9/244 • Number of events 10 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.	5.6% 13/231 • Number of events 21 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.
Musculoskeletal and connective tissue disorders Myalgia	19.3% 47/244 • Number of events 173 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.	22.9% 53/231 • Number of events 167 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.
Musculoskeletal and connective tissue disorders Pain in extremity	9.4% 23/244 • Number of events 36 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.	13.4% 31/231 • Number of events 49 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.
Nervous system disorders Dizziness	7.0% 17/244 • Number of events 24 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.	10.4% 24/231 • Number of events 35 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.
Nervous system disorders Headache	8.6% 21/244 • Number of events 26 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.	15.2% 35/231 • Number of events 48 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.
Nervous system disorders Neuropathy peripheral	26.6% 65/244 • Number of events 147 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.	25.1% 58/231 • Number of events 135 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.
Nervous system disorders Paraesthesia	6.1% 15/244 • Number of events 16 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.	3.9% 9/231 • Number of events 18 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.
Nervous system disorders Peripheral sensory neuropathy	20.5% 50/244 • Number of events 125 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.	23.4% 54/231 • Number of events 85 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.
Psychiatric disorders Insomnia	4.5% 11/244 • Number of events 18 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.	6.9% 16/231 • Number of events 19 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.
Respiratory, thoracic and mediastinal disorders Cough	10.2% 25/244 • Number of events 34 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.	9.5% 22/231 • Number of events 31 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.
Respiratory, thoracic and mediastinal disorders Dyspnoea	5.3% 13/244 • Number of events 19 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.	4.3% 10/231 • Number of events 13 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.
Skin and subcutaneous tissue disorders Alopecia	50.0% 122/244 • Number of events 153 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.	55.0% 127/231 • Number of events 151 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.
Skin and subcutaneous tissue disorders Pruritus	4.1% 10/244 • Number of events 14 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.	7.8% 18/231 • Number of events 24 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.
Skin and subcutaneous tissue disorders Rash	7.8% 19/244 • Number of events 27 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.	6.5% 15/231 • Number of events 39 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.
Vascular disorders Hypertension	4.1% 10/244 • Number of events 12 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.	6.1% 14/231 • Number of events 19 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.
Metabolism and nutrition disorders Hyperglycaemia	4.1% 10/244 • Number of events 31 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.	6.5% 15/231 • Number of events 36 • Adverse event (AE) reporting was extended from date of informed consent until completion of the final visit (up to approximately 57 months). At each level of summarization, patients were counted once if they reported one or more events.

Additional Information

Head of Clinical Planning Department

Celltrion

Phone: 82328505000

Email: contact@celltrion.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place