Trial Outcomes & Findings for Paclitaxel and Trastuzumab With or Without Lapatinib in Treating Patients With Stage II or Stage III Breast Cancer That Can Be Removed by Surgery (NCT NCT00770809)

Last Updated: 2025-08-15

Results Overview

Complete pathological response is defined as the absence of residual invasive carcinoma in the breast at the time of definitive surgical removal. Pathologic complete response in the lymph nodes is defined as no detectable invasive tumor by H\&E. Analysis will use a chi-square test for the difference in proportions of patients on the THL arm versus the TH arm who achieve a pCR. Exact binomial methods will be used to construct 95% confidence intervals around the pCR incidence for each arm.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

305 participants

Primary outcome timeframe

At time of surgery

Results posted on

2025-08-15

Participant Flow

Participant milestones

Participant milestones
Measure	Arm I (THL) Patients receive trastuzumab 2 mg/kg IV over 30-90 minutes and paclitaxel 80 mg/m\^2 IV over 1 hour once weekly and lapatinib ditosylate 750 mg PO once daily for 16 weeks in the absence of disease progression or unacceptable toxicity.	Arm II (TH) Patients receive trastuzumab 2 mg/kg IV over 30-90 minutes and paclitaxel 80 mg/m\^2 IV over 1 hour once weekly for 16 weeks in the absence of disease progression or unacceptable toxicity.	Arm III (TL) Patients receive paclitaxel 80 mg/m\^2 IV over 1 hour once weekly and lapatinib ditosylate 15000 mg PO once daily for 16 weeks in the absence of disease progression or unacceptable toxicity. (Discontinued as of 6-15-11)
Overall Study STARTED	118	120	67
Overall Study COMPLETED	101	110	44
Overall Study NOT COMPLETED	17	10	23

Reasons for withdrawal

Reasons for withdrawal
Measure	Arm I (THL) Patients receive trastuzumab 2 mg/kg IV over 30-90 minutes and paclitaxel 80 mg/m\^2 IV over 1 hour once weekly and lapatinib ditosylate 750 mg PO once daily for 16 weeks in the absence of disease progression or unacceptable toxicity.	Arm II (TH) Patients receive trastuzumab 2 mg/kg IV over 30-90 minutes and paclitaxel 80 mg/m\^2 IV over 1 hour once weekly for 16 weeks in the absence of disease progression or unacceptable toxicity.	Arm III (TL) Patients receive paclitaxel 80 mg/m\^2 IV over 1 hour once weekly and lapatinib ditosylate 15000 mg PO once daily for 16 weeks in the absence of disease progression or unacceptable toxicity. (Discontinued as of 6-15-11)
Overall Study Adverse Event	9	1	12
Overall Study Death	1	0	0
Overall Study Withdrawal by Subject	3	3	7
Overall Study Progression	2	2	0
Overall Study Complicating illness	0	0	1
Overall Study Other Medical Reasons	2	4	3

Baseline Characteristics

Paclitaxel and Trastuzumab With or Without Lapatinib in Treating Patients With Stage II or Stage III Breast Cancer That Can Be Removed by Surgery

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm I (THL) n=118 Participants Patients receive trastuzumab 2 mg/kg IV over 30-90 minutes and paclitaxel 80 mg/m\^2 IV over 1 hour once weekly and lapatinib ditosylate 750 mg PO once daily for 16 weeks in the absence of disease progression or unacceptable toxicity.	Arm II (TH) n=120 Participants Patients receive trastuzumab 2 mg/kg IV over 30-90 minutes and paclitaxel 80 mg/m\^2 IV over 1 hour once weekly for 16 weeks in the absence of disease progression or unacceptable toxicity.	Arm III (TL) n=67 Participants Patients receive paclitaxel 80 mg/m\^2 IV over 1 hour once weekly and lapatinib ditosylate 15000 mg PO once daily for 16 weeks in the absence of disease progression or unacceptable toxicity. (Discontinued as of 6-15-11)	Total n=305 Participants Total of all reporting groups
Age, Continuous	48.5 years n=5 Participants	50.3 years n=7 Participants	48.3 years n=5 Participants	49.4 years n=4 Participants
Sex: Female, Male Female	117 Participants n=5 Participants	119 Participants n=7 Participants	67 Participants n=5 Participants	303 Participants n=4 Participants
Sex: Female, Male Male	1 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants
Race (NIH/OMB) Asian	4 Participants n=5 Participants	8 Participants n=7 Participants	5 Participants n=5 Participants	17 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) Black or African American	12 Participants n=5 Participants	8 Participants n=7 Participants	7 Participants n=5 Participants	27 Participants n=4 Participants
Race (NIH/OMB) White	95 Participants n=5 Participants	97 Participants n=7 Participants	51 Participants n=5 Participants	243 Participants n=4 Participants
Race (NIH/OMB) More than one race	2 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	4 Participants n=5 Participants	5 Participants n=7 Participants	4 Participants n=5 Participants	13 Participants n=4 Participants
Region of Enrollment United States	118 participants n=5 Participants	120 participants n=7 Participants	67 participants n=5 Participants	305 participants n=4 Participants
Clinical Stage Stage II	81 participants n=5 Participants	80 participants n=7 Participants	48 participants n=5 Participants	209 participants n=4 Participants
Clinical Stage Stage III	37 participants n=5 Participants	40 participants n=7 Participants	19 participants n=5 Participants	96 participants n=4 Participants
Hormone Receptor Status ER/PgR Positive	70 participants n=5 Participants	70 participants n=7 Participants	39 participants n=5 Participants	179 participants n=4 Participants
Hormone Receptor Status ER/PgR or Negative	48 participants n=5 Participants	50 participants n=7 Participants	28 participants n=5 Participants	126 participants n=4 Participants

PRIMARY outcome

Timeframe: At time of surgery

Population: Participants who did not start protocol therapy or withdrew prior to surgery are excluded. Participants who did not undergo surgery are considered no having a pCR.

Outcome measures

Outcome measures
Measure	Arm I (THL) n=116 Participants Patients receive trastuzumab 2 mg/kg IV over 30-90 minutes and paclitaxel 80 mg/m\^2 IV over 1 hour once weekly and lapatinib ditosylate 750 mg PO once daily for 16 weeks in the absence of disease progression or unacceptable toxicity.	Arm II (TH) n=117 Participants Patients receive trastuzumab 2 mg/kg IV over 30-90 minutes and paclitaxel 80 mg/m\^2 IV over 1 hour once weekly for 16 weeks in the absence of disease progression or unacceptable toxicity.	Arm III (TL) n=63 Participants Patients receive paclitaxel 80 mg/m\^2 IV over 1 hour once weekly and lapatinib ditosylate 15000 mg PO once daily for 16 weeks in the absence of disease progression or unacceptable toxicity. (Discontinued as of 6-15-11)
pCR Rate	56 percentage of participants Interval 47.0 to 65.0	46 percentage of participants Interval 35.0 to 55.0	32 percentage of participants Interval 22.0 to 45.0

SECONDARY outcome

Timeframe: At time of surgery

Stage will be determined by the American Joint Committee on Cancer (AJCC) TNM (tumor, lymph nodes, metastasis) staging system.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Week 16

Response was defined by the Response Evaluation Criteria in Solid Tumors (RECIST). A responding participant had either a complete response (disappearance of all target lesions) or partial response (30% decrease in sum of longest diameter of target lesions).

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Time from randomization to death or last follow-up (up to 10 years)

Overall survival was measured as the interval from study entry until death, from any cause, or last contact. Distribution was estimated using the Kaplan Meier product-limit method

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Time from surgery to any recurrence (up to 10 years)

Relapse free survival is defined as the interval from definitive surgery to ipsilateral invasive breast tumor recurrence, regional invasive breast cancer recurrence, distant recurrence, or death from any cause, whichever occurs first. Patients who have not experienced any of these events will be censored at the date of last clinical assessment. Patients who do not undergo definitive surgery will not be assessable for RFS. Distribution was estimated using the Kaplan Meier product-limit method.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Time from study entry to any recurrence ( up to 10 years)

Time to first failure is defined as the interval from study entry to ipsilateral invasive breast tumor recurrence, regional invasive breast cancer recurrence, distant recurrence or death from any cause. Patients who have not experienced any of these events will be censored at the date of last clinical assessment. Distribution was estimated using the Kaplan Meier product-limit method.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 30 days post-treatment

The type and grade of treatment-related toxicity will be tabulated by treatment arm.

Outcome measures

Outcome data not reported

Adverse Events

Arm I (THL)

Serious events: 15 serious events

Other events: 114 other events

Deaths: 0 deaths

Arm II (TH)

Serious events: 12 serious events

Other events: 114 other events

Deaths: 0 deaths

Arm III (TL)

Serious events: 6 serious events

Other events: 64 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Lisa Carey, M.D.

University of North Carolina - Lineberger Comprehensive Cancer Center

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60

Measure	Arm I (THL) n=115 participants at risk Patients receive trastuzumab 2 mg/kg IV over 30-90 minutes and paclitaxel 80 mg/m\^2 IV over 1 hour once weekly and lapatinib ditosylate 750 mg PO once daily for 16 weeks in the absence of disease progression or unacceptable toxicity.	Arm II (TH) n=115 participants at risk Patients receive trastuzumab 2 mg/kg IV over 30-90 minutes and paclitaxel 80 mg/m\^2 IV over 1 hour once weekly for 16 weeks in the absence of disease progression or unacceptable toxicity.	Arm III (TL) n=65 participants at risk Patients receive paclitaxel 80 mg/m\^2 IV over 1 hour once weekly and lapatinib ditosylate 15000 mg PO once daily for 16 weeks in the absence of disease progression or unacceptable toxicity. (Discontinued as of 6-15-11)
Blood and lymphatic system disorders Febrile neutropenia	0.00% 0/115 Adverse Event data is available on 295 participants (Arm I: 115. Arm II: 115, Arm III: 65)	0.00% 0/115 Adverse Event data is available on 295 participants (Arm I: 115. Arm II: 115, Arm III: 65)	1.5% 1/65 • Number of events 1 Adverse Event data is available on 295 participants (Arm I: 115. Arm II: 115, Arm III: 65)
Blood and lymphatic system disorders Hemoglobin decreased	7.8% 9/115 • Number of events 11 Adverse Event data is available on 295 participants (Arm I: 115. Arm II: 115, Arm III: 65)	6.1% 7/115 • Number of events 8 Adverse Event data is available on 295 participants (Arm I: 115. Arm II: 115, Arm III: 65)	6.2% 4/65 • Number of events 5 Adverse Event data is available on 295 participants (Arm I: 115. Arm II: 115, Arm III: 65)
Cardiac disorders Cardiopulmonary arrest	0.87% 1/115 • Number of events 1 Adverse Event data is available on 295 participants (Arm I: 115. Arm II: 115, Arm III: 65)	0.00% 0/115 Adverse Event data is available on 295 participants (Arm I: 115. Arm II: 115, Arm III: 65)	0.00% 0/65 Adverse Event data is available on 295 participants (Arm I: 115. Arm II: 115, Arm III: 65)
Cardiac disorders Pericarditis	0.00% 0/115 Adverse Event data is available on 295 participants (Arm I: 115. Arm II: 115, Arm III: 65)	0.00% 0/115 Adverse Event data is available on 295 participants (Arm I: 115. Arm II: 115, Arm III: 65)	1.5% 1/65 • Number of events 1 Adverse Event data is available on 295 participants (Arm I: 115. Arm II: 115, Arm III: 65)
Gastrointestinal disorders Abdominal pain	0.87% 1/115 • Number of events 1 Adverse Event data is available on 295 participants (Arm I: 115. Arm II: 115, Arm III: 65)	0.87% 1/115 • Number of events 1 Adverse Event data is available on 295 participants (Arm I: 115. Arm II: 115, Arm III: 65)	0.00% 0/65 Adverse Event data is available on 295 participants (Arm I: 115. Arm II: 115, Arm III: 65)
Gastrointestinal disorders Constipation	0.00% 0/115 Adverse Event data is available on 295 participants (Arm I: 115. Arm II: 115, Arm III: 65)	0.00% 0/115 Adverse Event data is available on 295 participants (Arm I: 115. Arm II: 115, Arm III: 65)	1.5% 1/65 • Number of events 1 Adverse Event data is available on 295 participants (Arm I: 115. Arm II: 115, Arm III: 65)
Gastrointestinal disorders Diarrhea	10.4% 12/115 • Number of events 16 Adverse Event data is available on 295 participants (Arm I: 115. Arm II: 115, Arm III: 65)	4.3% 5/115 • Number of events 5 Adverse Event data is available on 295 participants (Arm I: 115. Arm II: 115, Arm III: 65)	7.7% 5/65 • Number of events 6 Adverse Event data is available on 295 participants (Arm I: 115. Arm II: 115, Arm III: 65)
Gastrointestinal disorders Nausea	6.1% 7/115 • Number of events 9 Adverse Event data is available on 295 participants (Arm I: 115. Arm II: 115, Arm III: 65)	1.7% 2/115 • Number of events 3 Adverse Event data is available on 295 participants (Arm I: 115. Arm II: 115, Arm III: 65)	3.1% 2/65 • Number of events 2 Adverse Event data is available on 295 participants (Arm I: 115. Arm II: 115, Arm III: 65)
Gastrointestinal disorders Pancreatitis	0.87% 1/115 • Number of events 1 Adverse Event data is available on 295 participants (Arm I: 115. Arm II: 115, Arm III: 65)	0.00% 0/115 Adverse Event data is available on 295 participants (Arm I: 115. Arm II: 115, Arm III: 65)	1.5% 1/65 • Number of events 1 Adverse Event data is available on 295 participants (Arm I: 115. Arm II: 115, Arm III: 65)
Gastrointestinal disorders Vomiting	2.6% 3/115 • Number of events 3 Adverse Event data is available on 295 participants (Arm I: 115. Arm II: 115, Arm III: 65)	0.87% 1/115 • Number of events 1 Adverse Event data is available on 295 participants (Arm I: 115. Arm II: 115, Arm III: 65)	1.5% 1/65 • Number of events 1 Adverse Event data is available on 295 participants (Arm I: 115. Arm II: 115, Arm III: 65)
General disorders Edema limbs	0.00% 0/115 Adverse Event data is available on 295 participants (Arm I: 115. Arm II: 115, Arm III: 65)	0.87% 1/115 • Number of events 1 Adverse Event data is available on 295 participants (Arm I: 115. Arm II: 115, Arm III: 65)	0.00% 0/65 Adverse Event data is available on 295 participants (Arm I: 115. Arm II: 115, Arm III: 65)
General disorders Fatigue	9.6% 11/115 • Number of events 15 Adverse Event data is available on 295 participants (Arm I: 115. Arm II: 115, Arm III: 65)	7.0% 8/115 • Number of events 9 Adverse Event data is available on 295 participants (Arm I: 115. Arm II: 115, Arm III: 65)	6.2% 4/65 • Number of events 4 Adverse Event data is available on 295 participants (Arm I: 115. Arm II: 115, Arm III: 65)
Immune system disorders Hypersensitivity	0.87% 1/115 • Number of events 1 Adverse Event data is available on 295 participants (Arm I: 115. Arm II: 115, Arm III: 65)	0.87% 1/115 • Number of events 1 Adverse Event data is available on 295 participants (Arm I: 115. Arm II: 115, Arm III: 65)	0.00% 0/65 Adverse Event data is available on 295 participants (Arm I: 115. Arm II: 115, Arm III: 65)
Infections and infestations Gallbladder infection	0.00% 0/115 Adverse Event data is available on 295 participants (Arm I: 115. Arm II: 115, Arm III: 65)	0.00% 0/115 Adverse Event data is available on 295 participants (Arm I: 115. Arm II: 115, Arm III: 65)	1.5% 1/65 • Number of events 1 Adverse Event data is available on 295 participants (Arm I: 115. Arm II: 115, Arm III: 65)
Infections and infestations Infection	0.87% 1/115 • Number of events 1 Adverse Event data is available on 295 participants (Arm I: 115. Arm II: 115, Arm III: 65)	0.00% 0/115 Adverse Event data is available on 295 participants (Arm I: 115. Arm II: 115, Arm III: 65)	0.00% 0/65 Adverse Event data is available on 295 participants (Arm I: 115. Arm II: 115, Arm III: 65)
Infections and infestations Pneumonia	0.00% 0/115 Adverse Event data is available on 295 participants (Arm I: 115. Arm II: 115, Arm III: 65)	0.87% 1/115 • Number of events 1 Adverse Event data is available on 295 participants (Arm I: 115. Arm II: 115, Arm III: 65)	0.00% 0/65 Adverse Event data is available on 295 participants (Arm I: 115. Arm II: 115, Arm III: 65)
Infections and infestations Sepsis	0.00% 0/115 Adverse Event data is available on 295 participants (Arm I: 115. Arm II: 115, Arm III: 65)	0.87% 1/115 • Number of events 1 Adverse Event data is available on 295 participants (Arm I: 115. Arm II: 115, Arm III: 65)	0.00% 0/65 Adverse Event data is available on 295 participants (Arm I: 115. Arm II: 115, Arm III: 65)
Infections and infestations Skin infection	0.00% 0/115 Adverse Event data is available on 295 participants (Arm I: 115. Arm II: 115, Arm III: 65)	0.87% 1/115 • Number of events 1 Adverse Event data is available on 295 participants (Arm I: 115. Arm II: 115, Arm III: 65)	0.00% 0/65 Adverse Event data is available on 295 participants (Arm I: 115. Arm II: 115, Arm III: 65)
Infections and infestations Soft tissue infection	0.00% 0/115 Adverse Event data is available on 295 participants (Arm I: 115. Arm II: 115, Arm III: 65)	0.87% 1/115 • Number of events 1 Adverse Event data is available on 295 participants (Arm I: 115. Arm II: 115, Arm III: 65)	0.00% 0/65 Adverse Event data is available on 295 participants (Arm I: 115. Arm II: 115, Arm III: 65)
Infections and infestations Urinary tract infection	1.7% 2/115 • Number of events 4 Adverse Event data is available on 295 participants (Arm I: 115. Arm II: 115, Arm III: 65)	0.00% 0/115 Adverse Event data is available on 295 participants (Arm I: 115. Arm II: 115, Arm III: 65)	0.00% 0/65 Adverse Event data is available on 295 participants (Arm I: 115. Arm II: 115, Arm III: 65)
Injury, poisoning and procedural complications Seroma	0.87% 1/115 • Number of events 1 Adverse Event data is available on 295 participants (Arm I: 115. Arm II: 115, Arm III: 65)	0.00% 0/115 Adverse Event data is available on 295 participants (Arm I: 115. Arm II: 115, Arm III: 65)	0.00% 0/65 Adverse Event data is available on 295 participants (Arm I: 115. Arm II: 115, Arm III: 65)
Investigations Alanine aminotransferase increased	0.87% 1/115 • Number of events 2 Adverse Event data is available on 295 participants (Arm I: 115. Arm II: 115, Arm III: 65)	1.7% 2/115 • Number of events 2 Adverse Event data is available on 295 participants (Arm I: 115. Arm II: 115, Arm III: 65)	4.6% 3/65 • Number of events 3 Adverse Event data is available on 295 participants (Arm I: 115. Arm II: 115, Arm III: 65)
Investigations Amylase increased	0.00% 0/115 Adverse Event data is available on 295 participants (Arm I: 115. Arm II: 115, Arm III: 65)	0.00% 0/115 Adverse Event data is available on 295 participants (Arm I: 115. Arm II: 115, Arm III: 65)	1.5% 1/65 • Number of events 1 Adverse Event data is available on 295 participants (Arm I: 115. Arm II: 115, Arm III: 65)
Investigations Aspartate aminotransferase increased	1.7% 2/115 • Number of events 3 Adverse Event data is available on 295 participants (Arm I: 115. Arm II: 115, Arm III: 65)	0.87% 1/115 • Number of events 1 Adverse Event data is available on 295 participants (Arm I: 115. Arm II: 115, Arm III: 65)	3.1% 2/65 • Number of events 2 Adverse Event data is available on 295 participants (Arm I: 115. Arm II: 115, Arm III: 65)
Investigations Leukocyte count decreased	0.00% 0/115 Adverse Event data is available on 295 participants (Arm I: 115. Arm II: 115, Arm III: 65)	0.00% 0/115 Adverse Event data is available on 295 participants (Arm I: 115. Arm II: 115, Arm III: 65)	1.5% 1/65 • Number of events 1 Adverse Event data is available on 295 participants (Arm I: 115. Arm II: 115, Arm III: 65)
Investigations Lipase increased	0.00% 0/115 Adverse Event data is available on 295 participants (Arm I: 115. Arm II: 115, Arm III: 65)	0.87% 1/115 • Number of events 1 Adverse Event data is available on 295 participants (Arm I: 115. Arm II: 115, Arm III: 65)	0.00% 0/65 Adverse Event data is available on 295 participants (Arm I: 115. Arm II: 115, Arm III: 65)
Investigations Neutrophil count decreased	4.3% 5/115 • Number of events 6 Adverse Event data is available on 295 participants (Arm I: 115. Arm II: 115, Arm III: 65)	2.6% 3/115 • Number of events 4 Adverse Event data is available on 295 participants (Arm I: 115. Arm II: 115, Arm III: 65)	3.1% 2/65 • Number of events 2 Adverse Event data is available on 295 participants (Arm I: 115. Arm II: 115, Arm III: 65)
Metabolism and nutrition disorders Dehydration	0.00% 0/115 Adverse Event data is available on 295 participants (Arm I: 115. Arm II: 115, Arm III: 65)	0.87% 1/115 • Number of events 1 Adverse Event data is available on 295 participants (Arm I: 115. Arm II: 115, Arm III: 65)	1.5% 1/65 • Number of events 1 Adverse Event data is available on 295 participants (Arm I: 115. Arm II: 115, Arm III: 65)
Metabolism and nutrition disorders Serum potassium decreased	2.6% 3/115 • Number of events 3 Adverse Event data is available on 295 participants (Arm I: 115. Arm II: 115, Arm III: 65)	0.00% 0/115 Adverse Event data is available on 295 participants (Arm I: 115. Arm II: 115, Arm III: 65)	1.5% 1/65 • Number of events 1 Adverse Event data is available on 295 participants (Arm I: 115. Arm II: 115, Arm III: 65)
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/115 Adverse Event data is available on 295 participants (Arm I: 115. Arm II: 115, Arm III: 65)	0.87% 1/115 • Number of events 1 Adverse Event data is available on 295 participants (Arm I: 115. Arm II: 115, Arm III: 65)	0.00% 0/65 Adverse Event data is available on 295 participants (Arm I: 115. Arm II: 115, Arm III: 65)
Musculoskeletal and connective tissue disorders Bone pain	0.00% 0/115 Adverse Event data is available on 295 participants (Arm I: 115. Arm II: 115, Arm III: 65)	0.87% 1/115 • Number of events 1 Adverse Event data is available on 295 participants (Arm I: 115. Arm II: 115, Arm III: 65)	0.00% 0/65 Adverse Event data is available on 295 participants (Arm I: 115. Arm II: 115, Arm III: 65)
Musculoskeletal and connective tissue disorders Chest wall pain	0.87% 1/115 • Number of events 2 Adverse Event data is available on 295 participants (Arm I: 115. Arm II: 115, Arm III: 65)	0.00% 0/115 Adverse Event data is available on 295 participants (Arm I: 115. Arm II: 115, Arm III: 65)	1.5% 1/65 • Number of events 1 Adverse Event data is available on 295 participants (Arm I: 115. Arm II: 115, Arm III: 65)
Musculoskeletal and connective tissue disorders Myalgia	2.6% 3/115 • Number of events 3 Adverse Event data is available on 295 participants (Arm I: 115. Arm II: 115, Arm III: 65)	1.7% 2/115 • Number of events 3 Adverse Event data is available on 295 participants (Arm I: 115. Arm II: 115, Arm III: 65)	0.00% 0/65 Adverse Event data is available on 295 participants (Arm I: 115. Arm II: 115, Arm III: 65)
Nervous system disorders Headache	0.00% 0/115 Adverse Event data is available on 295 participants (Arm I: 115. Arm II: 115, Arm III: 65)	0.87% 1/115 • Number of events 1 Adverse Event data is available on 295 participants (Arm I: 115. Arm II: 115, Arm III: 65)	0.00% 0/65 Adverse Event data is available on 295 participants (Arm I: 115. Arm II: 115, Arm III: 65)
Nervous system disorders Peripheral sensory neuropathy	5.2% 6/115 • Number of events 7 Adverse Event data is available on 295 participants (Arm I: 115. Arm II: 115, Arm III: 65)	3.5% 4/115 • Number of events 4 Adverse Event data is available on 295 participants (Arm I: 115. Arm II: 115, Arm III: 65)	1.5% 1/65 • Number of events 1 Adverse Event data is available on 295 participants (Arm I: 115. Arm II: 115, Arm III: 65)
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/115 Adverse Event data is available on 295 participants (Arm I: 115. Arm II: 115, Arm III: 65)	0.87% 1/115 • Number of events 1 Adverse Event data is available on 295 participants (Arm I: 115. Arm II: 115, Arm III: 65)	0.00% 0/65 Adverse Event data is available on 295 participants (Arm I: 115. Arm II: 115, Arm III: 65)
Skin and subcutaneous tissue disorders Alopecia	0.87% 1/115 • Number of events 2 Adverse Event data is available on 295 participants (Arm I: 115. Arm II: 115, Arm III: 65)	0.00% 0/115 Adverse Event data is available on 295 participants (Arm I: 115. Arm II: 115, Arm III: 65)	0.00% 0/65 Adverse Event data is available on 295 participants (Arm I: 115. Arm II: 115, Arm III: 65)
Skin and subcutaneous tissue disorders Rash desquamating	4.3% 5/115 • Number of events 7 Adverse Event data is available on 295 participants (Arm I: 115. Arm II: 115, Arm III: 65)	1.7% 2/115 • Number of events 3 Adverse Event data is available on 295 participants (Arm I: 115. Arm II: 115, Arm III: 65)	6.2% 4/65 • Number of events 4 Adverse Event data is available on 295 participants (Arm I: 115. Arm II: 115, Arm III: 65)
Vascular disorders Hypertension	0.00% 0/115 Adverse Event data is available on 295 participants (Arm I: 115. Arm II: 115, Arm III: 65)	0.87% 1/115 • Number of events 1 Adverse Event data is available on 295 participants (Arm I: 115. Arm II: 115, Arm III: 65)	0.00% 0/65 Adverse Event data is available on 295 participants (Arm I: 115. Arm II: 115, Arm III: 65)
Vascular disorders Hypotension	0.00% 0/115 Adverse Event data is available on 295 participants (Arm I: 115. Arm II: 115, Arm III: 65)	0.00% 0/115 Adverse Event data is available on 295 participants (Arm I: 115. Arm II: 115, Arm III: 65)	1.5% 1/65 • Number of events 1 Adverse Event data is available on 295 participants (Arm I: 115. Arm II: 115, Arm III: 65)
Vascular disorders Thrombosis	0.87% 1/115 • Number of events 2 Adverse Event data is available on 295 participants (Arm I: 115. Arm II: 115, Arm III: 65)	0.00% 0/115 Adverse Event data is available on 295 participants (Arm I: 115. Arm II: 115, Arm III: 65)	0.00% 0/65 Adverse Event data is available on 295 participants (Arm I: 115. Arm II: 115, Arm III: 65)