A Study Of Sunitinib In Combination With Capecitabine Compared With Capecitabine In Patients With Breast Cancer

• Sponsor: Pfizer (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00435409
• Collaborator: (none)
• Enrollment: 442
• Locations: 169
• Arms: 2
• Duration (Months): 51.9
• Patients Per Site: 2.6
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The treatment received with sunitinib plus capecitabine could delay tumor growth longer than with treatment with capecitabine alone.

Condition or Disease	Intervention/Treatment	Phase
Breast Neoplasms	Drug: Sunitinib + Capecitabine; Drug: Capecitabine	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 442 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized, Phase 3 Study Of Sunitinib In Combination With Capecitabine Compared With Capecitabine In Patients With Previously Treated Breast Cancer
• Study Start Date: Feb 1, 2007
• Actual Primary Completion Date: Dec 1, 2009
• Actual Study Completion Date: Jun 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: A	Drug: Sunitinib + Capecitabine; Sunitinib administered orally at a starting dose of 37.5 mg once a day on a continuous regimen. Capecitabine administered orally at a starting dose of 2000 mg/m^2 per day [1000 mg/m^2 bid (twice daily)] from days 1-14 every 3 weeks. Study treatment should be given until progression or withdrawal from the study for other reasons.
Active Comparator: B	Drug: Capecitabine; Capecitabine administered orally at a starting dose of 2500 mg/m^2 per day [1250 mg/m^2 bid (twice daily)] from days 1-14 every 3 weeks. Study treatment should be given until progression or withdrawal from the study for other reasons. At the time of progression, patients may be eligible to crossover to single agent sunitinib, administered orally at a starting dose of 37.5 mg daily.

Outcome Measures

Primary Outcome Measures

1. Progression Free Survival (PFS) [Baseline until disease progression (up to 3 years from first dose)]

   Defined as the time from the date of randomization to the date of the first documentation of objective tumor progression or death due to any cause, whichever occurs first. If tumor progression data include more than 1 date, the first date will be used. PFS (in months) will be calculated as (first event date minus randomization date plus 1) divided by 30.4.

Secondary Outcome Measures

1. Percentage of Participants With Objective Response (OR) [Baseline until response or disease progression (up to 3 years from first dose)]

   Proportion of participants with confirmed complete response (CR) or partial response (PR) according to the Response Evaluation Criteria in Solid Tumors (RECIST); CR: disappearance of all target lesions, PR: greater than or equal to (>=) 30 percent (%) decrease in the sum of the longest dimensions (SLD) of the target lesions taking as a reference the baseline SLD. Confirmed responses = persist on repeat imaging study at least 4 weeks after initial documentation of response. Designation of best response of stable disease (SD) required the criteria to be met at least 5 weeks after randomization.

2. Duration of Response (DR) [Baseline until response or disease progression (up to 3 years from first dose)]

   Time from the first documentation of objective tumor response (CR or PR) that was subsequently confirmed to the first documentation of disease progression (PD) or to death due to any cause, whichever occurred first. If tumor progression data included more than 1 date, the first date was used. DR (in months) was calculated as [the date response ended (date of PD or death) minus first CR or PR date that was subsequently confirmed plus 1)] divided by 30.4.

3. Overall Survival (OS) [Baseline until death or up to 3 years from first dose]

   Time from the date of randomization to the date of death due to any cause. OS (in months) calculated as (date of death minus randomization date plus 1) divided by 30.4. For patients lacking survival data beyond the date of their last follow-up, the OS time was censored on the last date they were known to be alive. Patients lacking survival data beyond randomization had their OS times censored at randomization.

4. Percent Chance of Participant Survival [Year 1, Year 2, Year 3]

   Probability of survival 2 years and 3 years after the first dose of study treatment.

5. Change From Baseline in European Organization for Research and Treatment of Cancer's Quality of Life Questionnaire (EORTC QLQ-C30) [Day 1 of each treatment cycle (up to 3 years or end of treatment)]

   EORTC QLQ-C30: global health/quality of life (QoL), functional domains (physical, role, cognitive, emotional, social), and symptom scales/items (fatigue, nausea and vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea). Recall period: past week; response range: not at all to very much; global/QoL range: very poor to excellent. Scale score range: 0 to 100. Higher functional/global QoL score = better functioning and higher symptom score = greater degree of symptoms

6. Change From Baseline in European Organization for Research and Treatment of Cancer's Quality of Life Questionnaire Breast Cancer Module (EORTC QLQ-BR23) [Day 1 of each treatment cycle (up to 3 years or end of treatment)]

   BR23: measured disease related symptoms of dry mouth, eye pain, hair loss, hot flushes, attractiveness, future health, sexual activity, arm/shoulder pain, breast pain, swollen breast, and skin problems on the breast. Recall period: past week; response range: not at all to very much. Scale score range: 0 to 100. Higher symptom score = greater degree of symptoms.

7. Change From Baseline in EuroQol Group's EuroQol 5-Dimensional Self-Report Questionnaire (EQ-5D) [Day 1 of each treatment cycle (up to 3 years or end of treatment)]

   EQ-5D: health status in 5 dimensions (mobility, self-care, pain/discomfort, anxiety/depression, usual activities). Three-level scale (1=no problem, 2=some problem, and 3=extreme problem). A single score between 1 and 3 is generated for each domain. For each subject, the outcome rating on the 5 domains could be mapped to a single index through an algorithm. The index ranges between 0 and 1, with the higher score indicating a better health state perceived by the participant.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Locally advanced or metastatic disease that can be measured. Patients with bone-only disease are also allowed to enter the study.

• Previous treatment with an anthracycline and a taxane in any setting

• Progression on first or second line regimen or adjuvant regimen if disease free interval less than 12 months

Exclusion Criteria:

• History of inflammatory carcinoma if there is no other measurable disease

• More than 2 chemotherapy agents in the advanced disease setting

• Brain metastases

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Pfizer Investigational Site	Downey	California	United States	90241
2	Pfizer Investigational Site	Fresno	California	United States	93720
3	Pfizer Investigational Site	Montebello	California	United States	90640
4	Pfizer Investigational Site	Whittier	California	United States	90606
5	Pfizer Investigational Site	Boca Raton	Florida	United States	33428
6	Pfizer Investigational Site	Boynton Beach	Florida	United States	33437
7	Pfizer Investigational Site	Coral Springs	Florida	United States	33065
8	Pfizer Investigational Site	Hollywood	Florida	United States	33021
9	Pfizer Investigational Site	Lake Worth	Florida	United States	33467
10	Pfizer Investigational Site	Lakeland	Florida	United States	33805
11	Pfizer Investigational Site	Miami	Florida	United States	33125
12	Pfizer Investigational Site	Miami	Florida	United States	33129
13	Pfizer Investigational Site	Miami	Florida	United States	33133
14	Pfizer Investigational Site	Pembroke Pines	Florida	United States	33028
15	Pfizer Investigational Site	Duluth	Georgia	United States	30096
16	Pfizer Investigational Site	Lawrenceville	Georgia	United States	30045
17	Pfizer Investigational Site	Snellville	Georgia	United States	30078
18	Pfizer Investigational Site	Avon	Indiana	United States	46123
19	Pfizer Investigational Site	Indianapolis	Indiana	United States	46260
20	Pfizer Investigational Site	Mooresville	Indiana	United States	46158
21	Pfizer Investigational Site	Covington	Louisiana	United States	70433
22	Pfizer Investigational Site	Gretna	Louisiana	United States	70056
23	Pfizer Investigational Site	Marrero	Louisiana	United States	70072
24	Pfizer Investigational Site	Metairie	Louisiana	United States	70002
25	Pfizer Investigational Site	Metairie	Louisiana	United States	70006
26	Pfizer Investigational Site	New Orleans	Louisiana	United States	70115
27	Pfizer Investigational Site	Shreveport	Louisiana	United States	71103
28	Pfizer Investigational Site	Kensington	Maryland	United States	20895
29	Pfizer Investigational Site	Rockville	Maryland	United States	20850
30	Pfizer Investigational Site	Corinth	Mississippi	United States	38834
31	Pfizer Investigational Site	Columbia	Missouri	United States	65201
32	Pfizer Investigational Site	Billings	Montana	United States	59101
33	Pfizer Investigational Site	Albuquerque	New Mexico	United States	87106
34	Pfizer Investigational Site	Albuquerque	New Mexico	United States	87109
35	Pfizer Investigational Site	Charlotte	North Carolina	United States	28203
36	Pfizer Investigational Site	Charlotte	North Carolina	United States	28204
37	Pfizer Investigational Site	Charlotte	North Carolina	United States	28211
38	Pfizer Investigational Site	Charlotte	North Carolina	United States	28262
39	Pfizer Investigational Site	Charlotte	North Carolina	United States	28277
40	Pfizer Investigational Site	Norman	Oklahoma	United States	73071
41	Pfizer Investigational Site	Oklahoma City	Oklahoma	United States	73120
42	Pfizer Investigational Site	Tulsa	Oklahoma	United States	74104
43	Pfizer Investigational Site	Tulsa	Oklahoma	United States	74133
44	Pfizer Investigational Site	Tulsa	Oklahoma	United States	74136
45	Pfizer Investigational Site	Clairton	Pennsylvania	United States	15025
46	Pfizer Investigational Site	Greensburg	Pennsylvania	United States	15601
47	Pfizer Investigational Site	Pittsburgh	Pennsylvania	United States	15213
48	Pfizer Investigational Site	Pittsburgh	Pennsylvania	United States	15232
49	Pfizer Investigational Site	Pottstown	Pennsylvania	United States	19464
50	Pfizer Investigational Site	Wexford	Pennsylvania	United States	15090
51	Pfizer Investigational Site	Franklin	Tennessee	United States	37067
52	Pfizer Investigational Site	Gallatin	Tennessee	United States	37066
53	Pfizer Investigational Site	Hermitage	Tennessee	United States	37076
54	Pfizer Investigational Site	Lebanon	Tennessee	United States	37087
55	Pfizer Investigational Site	Memphis	Tennessee	United States	38120
56	Pfizer Investigational Site	Murfreesboro	Tennessee	United States	37130
57	Pfizer Investigational Site	Nashville	Tennessee	United States	37203
58	Pfizer Investigational Site	Nashville	Tennessee	United States	37205
59	Pfizer Investigational Site	Nashville	Tennessee	United States	37207
60	Pfizer Investigational Site	Nashville	Tennessee	United States	37211
61	Pfizer Investigational Site	Smyrna	Tennessee	United States	37167
62	Pfizer Investigational Site	Austin	Texas	United States	78705
63	Pfizer Investigational Site	Austin	Texas	United States	78745
64	Pfizer Investigational Site	Austin	Texas	United States	78757
65	Pfizer Investigational Site	Austin	Texas	United States	78759
66	Pfizer Investigational Site	Beaumont	Texas	United States	77701
67	Pfizer Investigational Site	Corpus Christi	Texas	United States	78405
68	Pfizer Investigational Site	Corpus Christi	Texas	United States	78410
69	Pfizer Investigational Site	Georgetown	Texas	United States	78626
70	Pfizer Investigational Site	Bountiful	Utah	United States	84010
71	Pfizer Investigational Site	Layton	Utah	United States	84041
72	Pfizer Investigational Site	Murray	Utah	United States	84157
73	Pfizer Investigational Site	Salt Lake City	Utah	United States	84102
74	Pfizer Investigational Site	Salt Lake City	Utah	United States	84106
75	Pfizer Investigational Site	West Provo	Utah	United States	84604
76	Pfizer Investigational Site	West Valley City	Utah	United States	84120
77	Pfizer Investigational Site	Richmond	Virginia	United States	23235
78	Pfizer Investigational Site	Richmond	Virginia	United States	23298-0037
79	Pfizer Investigational Site	Kennewick	Washington	United States	99336
80	Pfizer Investigational Site	Linz		Austria	4010
81	Pfizer Investigational Site	Salzburg		Austria	A-5020
82	Pfizer Investigational Site	Wels		Austria	A-4600
83	Pfizer Investigational Site	Leuven		Belgium	3000
84	Pfizer Investigational Site	Liege		Belgium	4000
85	Pfizer Investigational Site	Namur		Belgium	5000
86	Pfizer Investigational Site	Turnhout		Belgium	2300
87	Pfizer Investigational Site	Yvoir		Belgium	5530
88	Pfizer Investigational Site	Calgary	Alberta	Canada	T2N 4N2
89	Pfizer Investigational Site	Calgary	Alberta	Canada	T2S 3C3
90	Pfizer Investigational Site	Oshawa	Ontario	Canada	L1G 2B9
91	Pfizer Investigational Site	Montreal	Quebec	Canada	H2W 1T8
92	Pfizer Investigational Site	Montreal	Quebec	Canada	H3A 1A1
93	Pfizer Investigational Site	Montreal	Quebec	Canada	H3G 1A4
94	Pfizer Investigational Site	Montreal	Quebec	Canada	H3T 1E2
95	Pfizer Investigational Site	Montreal	Quebec	Canada	H3T 1M5
96	Pfizer Investigational Site	Praha 4		Czech Republic	140 59
97	Pfizer Investigational Site	Praha 5		Czech Republic	150 06
98	Pfizer Investigational Site	Praha 5		Czech Republic	15006
99	Pfizer Investigational Site	Aalborg		Denmark	9100
100	Pfizer Investigational Site	Koebenhavn OE		Denmark	2100
101	Pfizer Investigational Site	Odense		Denmark	5000
102	Pfizer Investigational Site	Montpellier	Cedex 05	France	34059
103	Pfizer Investigational Site	Angers cedex 01		France	49033
104	Pfizer Investigational Site	BORDEAUX Cedex		France	33076
105	Pfizer Investigational Site	CAEN Cedex 5		France	14076
106	Pfizer Investigational Site	Lyon		France	Cedex 08
107	Pfizer Investigational Site	Nancy		France	54100
108	Pfizer Investigational Site	Paris		France	75231
109	Pfizer Investigational Site	Erlangen		Germany	91054
110	Pfizer Investigational Site	Frankenthal		Germany	67227
111	Pfizer Investigational Site	Frankfurt am Main		Germany	60590
112	Pfizer Investigational Site	Fuerstenwalde		Germany	15517
113	Pfizer Investigational Site	Goettingen		Germany	37099
114	Pfizer Investigational Site	Muenster		Germany	48149
115	Pfizer Investigational Site	Nuernberg		Germany	90419
116	Pfizer Investigational Site	Stendal		Germany	39576
117	Pfizer Investigational Site	Ulm		Germany	89075
118	Pfizer Investigational Site	Voelklingen		Germany	66333
119	Pfizer Investigational Site	Heraklion	Crete	Greece	71 110
120	Pfizer Investigational Site	Athens		Greece	18547
121	Pfizer Investigational Site	Ioannina		Greece	45 110
122	Pfizer Investigational Site	Patras		Greece	26500
123	Pfizer Investigational Site	Thessaloniki		Greece	564 03
124	Pfizer Investigational Site	Dublin		Ireland	4
125	Pfizer Investigational Site	Dublin		Ireland	7
126	Pfizer Investigational Site	Dublin		Ireland	8
127	Pfizer Investigational Site	Bologna		Italy	40138
128	Pfizer Investigational Site	Brescia		Italy	25123
129	Pfizer Investigational Site	Messina		Italy	98122
130	Pfizer Investigational Site	Milano		Italy	20148
131	Pfizer Investigational Site	Palermo		Italy	90127
132	Pfizer Investigational Site	Parma		Italy	43100
133	Pfizer Investigational Site	Roma		Italy	00133
134	Pfizer Investigational Site	Roma		Italy	00144
135	Pfizer Investigational Site	Saronno (VA)		Italy	21047
136	Pfizer Investigational Site	Torino		Italy	10126
137	Pfizer Investigational Site	Amsterdam		Netherlands	1081 HV
138	Pfizer Investigational Site	Sittard-geleen		Netherlands	6162 BG
139	Pfizer Investigational Site	Zwolle		Netherlands	8025 AB
140	Pfizer Investigational Site	Levanger		Norway	7600
141	Pfizer Investigational Site	Oslo		Norway	0407
142	Pfizer Investigational Site	Lodz		Poland	93-509
143	Pfizer Investigational Site	Lublin		Poland	20-090
144	Pfizer Investigational Site	Warszawa		Poland	00-909
145	Pfizer Investigational Site	Warszawa		Poland	02-781
146	Pfizer Investigational Site	Cluj-Napoca	Cluj	Romania	400015
147	Pfizer Investigational Site	Bucuresti	Sector 2	Romania	022328
148	Pfizer Investigational Site	Kuzmolovo, Vsevolozhsk district	Leningrad region	Russian Federation	188663
149	Pfizer Investigational Site	Moscow		Russian Federation	143423
150	Pfizer Investigational Site	St. Petersburg		Russian Federation	191104
151	Pfizer Investigational Site	St. Petersburg		Russian Federation	197758
152	Pfizer Investigational Site	Barcelona		Spain	08036
153	Pfizer Investigational Site	Burgos		Spain	09005
154	Pfizer Investigational Site	Cadiz		Spain	11009
155	Pfizer Investigational Site	La Coruña		Spain	15009
156	Pfizer Investigational Site	Madrid		Spain	28034
157	Pfizer Investigational Site	Madrid		Spain	28046
158	Pfizer Investigational Site	Sevilla		Spain	41020
159	Pfizer Investigational Site	Truro	Cornwall	United Kingdom	TR1 3LJ
160	Pfizer Investigational Site	Chelmsford	Essex	United Kingdom	CM1 7WE
161	Pfizer Investigational Site	Harlow	Essex	United Kingdom	CM20 1QX
162	Pfizer Investigational Site	Burton upon Trent	Staffordshire	United Kingdom	DE13 0RB
163	Pfizer Investigational Site	Worthing	West Sussex	United Kingdom	BN11 2DH
164	Pfizer Investigational Site	Birmingham		United Kingdom	B15 2TH
165	Pfizer Investigational Site	Essex		United Kingdom	CM16 6TN
166	Pfizer Investigational Site	London		United Kingdom	W6 8RF
167	Pfizer Investigational Site	Swansea		United Kingdom	SA2 8QA
168	Pfizer Investigational Site	Truro		United Kingdom	TR1 3LJ
169	Pfizer Investigational Site	Worthing		United Kingdom	BN11 2DH

Sponsors and Collaborators

• Pfizer

Investigators

• Study Director: Pfizer CT.gov Call Center, Pfizer

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• To obtain contact information for a study center near you, click here.

Publications

None provided.

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT00435409
• Other Study ID Numbers: A6181099
• First Posted: Feb 15, 2007
• Last Update Posted: Jun 26, 2012
• Last Verified: Jun 1, 2012

• Additional relevant MeSH terms: Breast Neoplasms; Capecitabine; Sunitinib

Study Results

Participant Flow

Arm/Group Title	Sunitinib + Capecitabine	Capecitabine, no Crossover	Capecitabine, Crossover to Sunitinib
Arm/Group Description	Sunitinib administered orally at a starting dose of 37.5 milligrams (mg) once a day on a continuous regimen. Capecitabine administered orally at a starting dose of 2000 milligrams per square meter (mg/m^2) per day (1000 mg/m^2 twice daily [BID]) from Days 1-14 every 3 weeks.	Capecitabine administered orally at a starting dose of 2500 mg/m^2 per day (1250 mg/m^2 BID) from Days 1-14 every 3 weeks.	Capecitabine administered orally at a starting dose of 2500 mg/m^2 per day (1250 mg/m^2 BID) from Days 1-14 every 3 weeks. At the time of progression, crossover to single agent sunitinib, administered orally at a starting dose of 37.5 mg daily continuously.
Period Title: Overall Study
STARTED	221	143	78
Treated	217	139	78
COMPLETED	0	0	0
NOT COMPLETED	221	143	78

Baseline Characteristics

Arm/Group Title	Sunitinib + Capecitabine	Capecitabine	Total
Arm/Group Description	Sunitinib administered orally at a starting dose of 37.5 mg once a day on a continuous regimen. Capecitabine administered orally at a starting dose of 2000 mg/m^2 per day (1000 mg/m^2 BID) from Days 1-14 every 3 weeks.	Capecitabine administered orally at a starting dose of 2500 mg/m^2 per day (1250 mg/m^2 BID) from Days 1-14 every 3 weeks. At the time of progression, participants could have been eligible to crossover to single agent sunitinib, administered orally at a starting dose of 37.5 mg daily continuously.	Total of all reporting groups
Overall Participants	221	221	442
Age, Customized (participants) [Number]
Less than 65 years	182 82.4%	185 83.7%	367 83%
Greater than or equal to 65 years	39 17.6%	36 16.3%	75 17%
Sex: Female, Male (Count of Participants)
Female	218 98.6%	220 99.5%	438 99.1%
Male	3 1.4%	1 0.5%	4 0.9%

Outcome Measures

1. Primary Outcome

Title	Progression Free Survival (PFS)
Description	Defined as the time from the date of randomization to the date of the first documentation of objective tumor progression or death due to any cause, whichever occurs first. If tumor progression data include more than 1 date, the first date will be used. PFS (in months) will be calculated as (first event date minus randomization date plus 1) divided by 30.4.
Time Frame	Baseline until disease progression (up to 3 years from first dose)

Outcome Measure Data

Analysis Population Description

Intent to treat (ITT) population: defined as all participants who were randomized

Arm/Group Title	Sunitinib + Capecitabine	Capecitabine
Arm/Group Description	Sunitinib administered orally at a starting dose of 37.5 mg once a day on a continuous regimen. Capecitabine administered orally at a starting dose of 2000 mg/m^2 per day (1000 mg/m^2 BID) from Days 1-14 every 3 weeks.	Capecitabine administered orally at a starting dose of 2500 mg/m^2 per day (1250 mg/m^2 BID) from Days 1-14 every 3 weeks. At the time of progression, participants could have been eligible to crossover to single agent sunitinib, administered orally at a starting dose of 37.5 mg daily continuously.
Measure Participants	221	221
Independent radiology assessment	5.5	5.9
Investigator's assessment	5.4	5.5

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sunitinib + Capecitabine, Capecitabine
	Comments	A stratified log-rank test (1-sided, α=0.025) based on randomization stratification factors
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.9409
	Comments	Stratification factors included metastatic organ sites (2 or less versus [vs] more than [>] 2 sites), hormone receptor status (HER2-/ER-/PR-) vs all others), and prior chemotherapy regimens (1 vs >1), from interactive voice response system (IVRS).
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.2239
	Confidence Interval	(2-Sided) 95%; 0.9487 to 1.5789
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Sunitinib + Capecitabine, Capecitabine
	Comments	A stratified log-rank test (1-sided, α=0.025) based on randomization stratification factors
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.8120
	Comments	Stratification factors include metastatic organ sites (2 or less versus [vs] 2 or more sites), hormone receptor status (HER2-/ER-/PR-) vs all others), and prior chemotherapy regimens (1 vs more than 1), from IVRS.
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.1084
	Confidence Interval	(2-Sided) 95%; 0.8817 to 1.3935
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Percentage of Participants With Objective Response (OR)
Description	Proportion of participants with confirmed complete response (CR) or partial response (PR) according to the Response Evaluation Criteria in Solid Tumors (RECIST); CR: disappearance of all target lesions, PR: greater than or equal to (>=) 30 percent (%) decrease in the sum of the longest dimensions (SLD) of the target lesions taking as a reference the baseline SLD. Confirmed responses = persist on repeat imaging study at least 4 weeks after initial documentation of response. Designation of best response of stable disease (SD) required the criteria to be met at least 5 weeks after randomization.
Time Frame	Baseline until response or disease progression (up to 3 years from first dose)

Outcome Measure Data

Analysis Population Description

ITT population

Arm/Group Title	Sunitinib + Capecitabine	Capecitabine
Arm/Group Description	Sunitinib administered orally at a starting dose of 37.5 mg once a day on a continuous regimen. Capecitabine administered orally at a starting dose of 2000 mg/m^2 per day (1000 mg/m^2 BID) from Days 1-14 every 3 weeks.	Capecitabine administered orally at a starting dose of 2500 mg/m^2 per day (1250 mg/m^2 BID) from Days 1-14 every 3 weeks. At the time of progression, participants could have been eligible to crossover to single agent sunitinib, administered orally at a starting dose of 37.5 mg daily continuously.
Measure Participants	221	221
Independent radiology assessment	18.6 8.4%	16.3 7.4%
Investigator's assessment	25.3 11.4%	20.4 9.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sunitinib + Capecitabine, Capecitabine
	Comments	Independent radiology assessment
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3143
	Comments	A stratified CMH test stratified by randomization stratification factors was used to compare objective response rate (ORR) between two treatment arms.
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.17
	Confidence Interval	(2-Sided) 95%; 0.69 to 1.97
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Sunitinib + Capecitabine, Capecitabine
	Comments	Investigator's assessment
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1269
	Comments	A stratified CMH test stratified by randomization stratification factors was used to compare ORR between two treatment arms.
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.32
	Confidence Interval	(2-Sided) 95%; 0.83 to 2.13
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Duration of Response (DR)
Description	Time from the first documentation of objective tumor response (CR or PR) that was subsequently confirmed to the first documentation of disease progression (PD) or to death due to any cause, whichever occurred first. If tumor progression data included more than 1 date, the first date was used. DR (in months) was calculated as [the date response ended (date of PD or death) minus first CR or PR date that was subsequently confirmed plus 1)] divided by 30.4.
Time Frame	Baseline until response or disease progression (up to 3 years from first dose)

Outcome Measure Data

Analysis Population Description

ITT subgroup of participants with a confirmed objective tumor response.

Arm/Group Title	Sunitinib + Capecitabine	Capecitabine
Arm/Group Description	Sunitinib administered orally at a starting dose of 37.5 mg once a day on a continuous regimen. Capecitabine administered orally at a starting dose of 2000 mg/m^2 per day (1000 mg/m^2 BID) from Days 1-14 every 3 weeks.	Capecitabine administered orally at a starting dose of 2500 mg/m^2 per day (1250 mg/m^2 BID) from Days 1-14 every 3 weeks. At the time of progression, participants could have been eligible to crossover to single agent sunitinib, administered orally at a starting dose of 37.5 mg daily continuously.
Measure Participants	41	36
Independent radiology assessment	9.0	8.8
Investigator's assessment	5.7	7.6

4. Secondary Outcome

Title	Overall Survival (OS)
Description	Time from the date of randomization to the date of death due to any cause. OS (in months) calculated as (date of death minus randomization date plus 1) divided by 30.4. For patients lacking survival data beyond the date of their last follow-up, the OS time was censored on the last date they were known to be alive. Patients lacking survival data beyond randomization had their OS times censored at randomization.
Time Frame	Baseline until death or up to 3 years from first dose

Outcome Measure Data

Analysis Population Description

ITT population

Arm/Group Title	Sunitinib + Capecitabine	Capecitabine
Arm/Group Description	Sunitinib administered orally at a starting dose of 37.5 mg once a day on a continuous regimen. Capecitabine administered orally at a starting dose of 2000 mg/m^2 per day (1000 mg/m^2 BID) from Days 1-14 every 3 weeks.	Capecitabine administered orally at a starting dose of 2500 mg/m^2 per day (1250 mg/m^2 BID) from Days 1-14 every 3 weeks. At the time of progression, participants could have been eligible to crossover to single agent sunitinib, administered orally at a starting dose of 37.5 mg daily continuously.
Measure Participants	221	221
Median (95% Confidence Interval) [months]	16.5	17.2

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sunitinib + Capecitabine, Capecitabine
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.6275
	Comments	Stratification factors (all from IVRS) included number of metastatic organ sites (<=2 vs >2 sites), hormone receptor status (HER2-/ER-/PR- vs all others), and prior chemotherapy regimens (1 vs >1).
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.0372
	Confidence Interval	(2-Sided) 95%; 0.8322 to 1.2927
	Parameter Dispersion	Type: Value:
	Estimation Comments	Hazard ratio for sunitinib + capecitabine versus capecitabine.

5. Secondary Outcome

Title	Percent Chance of Participant Survival
Description	Probability of survival 2 years and 3 years after the first dose of study treatment.
Time Frame	Year 1, Year 2, Year 3

Outcome Measure Data

Analysis Population Description

ITT population

Arm/Group Title	Sunitinib + Capecitabine	Capecitabine
Arm/Group Description	Sunitinib administered orally at a starting dose of 37.5 mg once a day on a continuous regimen. Capecitabine administered orally at a starting dose of 2000 mg/m^2 per day (1000 mg/m^2 BID) from Days 1-14 every 3 weeks.	Capecitabine administered orally at a starting dose of 2500 mg/m^2 per day (1250 mg/m^2 BID) from Days 1-14 every 3 weeks. At the time of progression, participants could have been eligible to crossover to single agent sunitinib, administered orally at a starting dose of 37.5 mg daily continuously.
Measure Participants	221	221
Year 1	0.635	0.654
Year 2	0.368	0.373
Year 3	0.150	0.174

6. Secondary Outcome

Title	Change From Baseline in European Organization for Research and Treatment of Cancer's Quality of Life Questionnaire (EORTC QLQ-C30)
Description	EORTC QLQ-C30: global health/quality of life (QoL), functional domains (physical, role, cognitive, emotional, social), and symptom scales/items (fatigue, nausea and vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea). Recall period: past week; response range: not at all to very much; global/QoL range: very poor to excellent. Scale score range: 0 to 100. Higher functional/global QoL score = better functioning and higher symptom score = greater degree of symptoms
Time Frame	Day 1 of each treatment cycle (up to 3 years or end of treatment)

Outcome Measure Data

Analysis Population Description

Patient Reported Outcomes (PRO) assessments were not analyzed because the study did not meet its primary endpoint.

Arm/Group Title	Sunitinib + Capecitabine	Capecitabine
Arm/Group Description	Sunitinib administered orally at a starting dose of 37.5 mg once a day on a continuous regimen. Capecitabine administered orally at a starting dose of 2000 mg/m^2 per day (1000 mg/m^2 BID) from Days 1-14 every 3 weeks.	Capecitabine administered orally at a starting dose of 2500 mg/m^2 per day (1250 mg/m^2 BID) from Days 1-14 every 3 weeks. At the time of progression, participants could have been eligible to crossover to single agent sunitinib, administered orally at a starting dose of 37.5 mg daily continuously.
Measure Participants	0	0

7. Secondary Outcome

Title	Change From Baseline in European Organization for Research and Treatment of Cancer's Quality of Life Questionnaire Breast Cancer Module (EORTC QLQ-BR23)
Description	BR23: measured disease related symptoms of dry mouth, eye pain, hair loss, hot flushes, attractiveness, future health, sexual activity, arm/shoulder pain, breast pain, swollen breast, and skin problems on the breast. Recall period: past week; response range: not at all to very much. Scale score range: 0 to 100. Higher symptom score = greater degree of symptoms.
Time Frame	Day 1 of each treatment cycle (up to 3 years or end of treatment)

Outcome Measure Data

Analysis Population Description

PRO assessments were not analyzed because the study did not meet its primary endpoint.

Arm/Group Title	Sunitinib + Capecitabine	Capecitabine
Arm/Group Description	Sunitinib administered orally at a starting dose of 37.5 mg once a day on a continuous regimen. Capecitabine administered orally at a starting dose of 2000 mg/m^2 per day (1000 mg/m^2 BID) from Days 1-14 every 3 weeks.	Capecitabine administered orally at a starting dose of 2500 mg/m^2 per day (1250 mg/m^2 BID) from Days 1-14 every 3 weeks. At the time of progression, participants could have been eligible to crossover to single agent sunitinib, administered orally at a starting dose of 37.5 mg daily continuously.
Measure Participants	0	0

8. Secondary Outcome

Title	Change From Baseline in EuroQol Group's EuroQol 5-Dimensional Self-Report Questionnaire (EQ-5D)
Description	EQ-5D: health status in 5 dimensions (mobility, self-care, pain/discomfort, anxiety/depression, usual activities). Three-level scale (1=no problem, 2=some problem, and 3=extreme problem). A single score between 1 and 3 is generated for each domain. For each subject, the outcome rating on the 5 domains could be mapped to a single index through an algorithm. The index ranges between 0 and 1, with the higher score indicating a better health state perceived by the participant.
Time Frame	Day 1 of each treatment cycle (up to 3 years or end of treatment)

Outcome Measure Data

Analysis Population Description

PRO assessments were not analyzed because the study did not meet its primary endpoint.

Arm/Group Title	Sunitinib + Capecitabine	Capecitabine
Arm/Group Description	Sunitinib administered orally at a starting dose of 37.5 mg once a day on a continuous regimen. Capecitabine administered orally at a starting dose of 2000 mg/m^2 per day (1000 mg/m^2 BID) from Days 1-14 every 3 weeks.	Capecitabine administered orally at a starting dose of 2500 mg/m^2 per day (1250 mg/m^2 BID) from Days 1-14 every 3 weeks. At the time of progression, participants could have been eligible to crossover to single agent sunitinib, administered orally at a starting dose of 37.5 mg daily continuously.
Measure Participants	0	0

Adverse Events

Adverse Event Reporting Description	The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Arm/Group Title	Sunitinib + Capecitabine		Capecitabine
Arm/Group Description	Sunitinib administered orally at a starting dose of 37.5 mg once a day on a continuous regimen. Capecitabine administered orally at a starting dose of 2000 mg/m^2 per day (1000 mg/m^2 BID) from Days 1-14 every 3 weeks.		Capecitabine administered orally at a starting dose of 2500 mg/m^2 per day (1250 mg/m^2 BID) from Days 1-14 every 3 weeks. At the time of progression, participants could have been eligible to crossover to single agent sunitinib, administered orally at a starting dose of 37.5 mg daily continuously.
All Cause Mortality
	Sunitinib + Capecitabine		Capecitabine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Sunitinib + Capecitabine		Capecitabine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	85/217 (39.2%)		59/215 (27.4%)
Blood and lymphatic system disorders
Anaemia	7/217 (3.2%)		1/215 (0.5%)
Bone marrow failure	1/217 (0.5%)		0/215 (0%)
Leukopenia	2/217 (0.9%)		0/215 (0%)
Neutropenia	3/217 (1.4%)		0/215 (0%)
Thrombocytopenia	7/217 (3.2%)		0/215 (0%)
Pancytopenia	1/217 (0.5%)		0/215 (0%)
Cardiac disorders
Cardiac failure acute	1/217 (0.5%)		0/215 (0%)
Congestive cardiomyopathy	0/217 (0%)		1/215 (0.5%)
Pericardial effusion	1/217 (0.5%)		0/215 (0%)
Supraventricular tachycardia	0/217 (0%)		1/215 (0.5%)
Ventricular extrasystoles	1/217 (0.5%)		0/215 (0%)
Ear and labyrinth disorders
Vertigo	1/217 (0.5%)		0/215 (0%)
Endocrine disorders
Hypothyroidism	2/217 (0.9%)		0/215 (0%)
Gastrointestinal disorders
Abdominal pain	2/217 (0.9%)		2/215 (0.9%)
Abdominal pain upper	1/217 (0.5%)		0/215 (0%)
Anal fissure	1/217 (0.5%)		0/215 (0%)
Ascites	1/217 (0.5%)		2/215 (0.9%)
Colitis	0/217 (0%)		1/215 (0.5%)
Colonic obstruction	0/217 (0%)		1/215 (0.5%)
Constipation	0/217 (0%)		2/215 (0.9%)
Diarrhoea	9/217 (4.1%)		13/215 (6%)
Diverticular perforation	1/217 (0.5%)		0/215 (0%)
Duodenal stenosis	0/217 (0%)		1/215 (0.5%)
Dyspepsia	1/217 (0.5%)		0/215 (0%)
Dysphagia	1/217 (0.5%)		1/215 (0.5%)
Enteritis	1/217 (0.5%)		0/215 (0%)
Gastritis	2/217 (0.9%)		1/215 (0.5%)
Gastrointestinal haemorrhage	1/217 (0.5%)		0/215 (0%)
Intestinal obstruction	0/217 (0%)		1/215 (0.5%)
Nausea	6/217 (2.8%)		1/215 (0.5%)
Pancreatitis haemorrhagic	1/217 (0.5%)		0/215 (0%)
Peritonitis	1/217 (0.5%)		0/215 (0%)
Small intestinal obstruction	1/217 (0.5%)		1/215 (0.5%)
Stomatitis	0/217 (0%)		1/215 (0.5%)
Subileus	2/217 (0.9%)		1/215 (0.5%)
Upper gastrointestinal haemorrhage	1/217 (0.5%)		0/215 (0%)
Vomiting	11/217 (5.1%)		6/215 (2.8%)
General disorders
Asthenia	6/217 (2.8%)		0/215 (0%)
Chest pain	1/217 (0.5%)		2/215 (0.9%)
Chills	0/217 (0%)		1/215 (0.5%)
Death	1/217 (0.5%)		0/215 (0%)
Disease progression	10/217 (4.6%)		7/215 (3.3%)
Fatigue	2/217 (0.9%)		2/215 (0.9%)
General physical health deterioration	3/217 (1.4%)		1/215 (0.5%)
Malaise	1/217 (0.5%)		0/215 (0%)
Mucosal inflammation	2/217 (0.9%)		1/215 (0.5%)
Pain	0/217 (0%)		1/215 (0.5%)
Pyrexia	2/217 (0.9%)		6/215 (2.8%)
Ulcer	0/217 (0%)		1/215 (0.5%)
HAEMATEMESIS SECONDARY TO THROMBCYTOPENIA	1/217 (0.5%)		0/215 (0%)
Hepatobiliary disorders
Cytolytic hepatitis	1/217 (0.5%)		0/215 (0%)
Hepatic failure	1/217 (0.5%)		0/215 (0%)
Hepatic haemorrhage	1/217 (0.5%)		0/215 (0%)
Hyperbilirubinaemia	1/217 (0.5%)		1/215 (0.5%)
Jaundice	1/217 (0.5%)		0/215 (0%)
Infections and infestations
Breast infection	1/217 (0.5%)		0/215 (0%)
Erysipelas	1/217 (0.5%)		0/215 (0%)
Gastroenteritis	0/217 (0%)		1/215 (0.5%)
Infection	1/217 (0.5%)		0/215 (0%)
Neutropenic sepsis	1/217 (0.5%)		1/215 (0.5%)
Pneumonia	2/217 (0.9%)		1/215 (0.5%)
Pyelonephritis	0/217 (0%)		1/215 (0.5%)
Sepsis	0/217 (0%)		3/215 (1.4%)
Tooth infection	1/217 (0.5%)		0/215 (0%)
Urinary tract infection	0/217 (0%)		1/215 (0.5%)
Cellulitis	1/217 (0.5%)		0/215 (0%)
Injury, poisoning and procedural complications
Fall	0/217 (0%)		1/215 (0.5%)
Hip fracture	0/217 (0%)		1/215 (0.5%)
Radiation skin injury	1/217 (0.5%)		0/215 (0%)
Radius fracture	0/217 (0%)		1/215 (0.5%)
Subdural haematoma	1/217 (0.5%)		0/215 (0%)
Wrist fracture	0/217 (0%)		1/215 (0.5%)
Investigations
Ejection fraction decreased	1/217 (0.5%)		0/215 (0%)
Electrocardiogram ST segment depression	1/217 (0.5%)		0/215 (0%)
Haemoglobin decreased	0/217 (0%)		2/215 (0.9%)
Metabolism and nutrition disorders
Decreased appetite	1/217 (0.5%)		0/215 (0%)
Dehydration	1/217 (0.5%)		1/215 (0.5%)
Diabetes mellitus	1/217 (0.5%)		0/215 (0%)
Hypercalcaemia	1/217 (0.5%)		0/215 (0%)
Hypokalaemia	1/217 (0.5%)		1/215 (0.5%)
Hyponatraemia	1/217 (0.5%)		0/215 (0%)
Musculoskeletal and connective tissue disorders
Back pain	1/217 (0.5%)		0/215 (0%)
Bone pain	1/217 (0.5%)		0/215 (0%)
Muscular weakness	1/217 (0.5%)		0/215 (0%)
Musculoskeletal chest pain	1/217 (0.5%)		0/215 (0%)
Myalgia	1/217 (0.5%)		0/215 (0%)
Osteolysis	0/217 (0%)		1/215 (0.5%)
Pain in extremity	0/217 (0%)		1/215 (0.5%)
Pathological fracture	0/217 (0%)		2/215 (0.9%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer	2/217 (0.9%)		1/215 (0.5%)
Lung neoplasm	0/217 (0%)		1/215 (0.5%)
Malignant pleural effusion	0/217 (0%)		1/215 (0.5%)
Nervous system disorders
Cerebral haemorrhage	1/217 (0.5%)		0/215 (0%)
Cerebrovascular accident	1/217 (0.5%)		1/215 (0.5%)
Convulsion	1/217 (0.5%)		0/215 (0%)
Diabetic coma	0/217 (0%)		1/215 (0.5%)
Facial paresis	1/217 (0.5%)		0/215 (0%)
Hypoaesthesia	0/217 (0%)		1/215 (0.5%)
Neuralgia	0/217 (0%)		1/215 (0.5%)
Paraplegia	1/217 (0.5%)		0/215 (0%)
Psychiatric disorders
Psychotic disorder	0/217 (0%)		1/215 (0.5%)
Renal and urinary disorders
Nephrolithiasis	0/217 (0%)		1/215 (0.5%)
Renal failure	1/217 (0.5%)		1/215 (0.5%)
Renal infarct	1/217 (0.5%)		0/215 (0%)
Renal pain	1/217 (0.5%)		0/215 (0%)
Reproductive system and breast disorders
Metrorrhagia	1/217 (0.5%)		1/215 (0.5%)
Respiratory, thoracic and mediastinal disorders
Cough	0/217 (0%)		1/215 (0.5%)
Dyspnoea	4/217 (1.8%)		3/215 (1.4%)
Haemoptysis	1/217 (0.5%)		2/215 (0.9%)
Hydrothorax	2/217 (0.9%)		0/215 (0%)
Pleural effusion	1/217 (0.5%)		3/215 (1.4%)
Pneumonitis	0/217 (0%)		1/215 (0.5%)
Pneumothorax	1/217 (0.5%)		1/215 (0.5%)
Pulmonary embolism	8/217 (3.7%)		2/215 (0.9%)
Skin and subcutaneous tissue disorders
Palmar-plantar erythrodysaesthesia syndrome	0/217 (0%)		3/215 (1.4%)
Surgical and medical procedures
Ureteral catheterisation	1/217 (0.5%)		0/215 (0%)
Vascular disorders
Hypertension	2/217 (0.9%)		0/215 (0%)
Iliac artery thrombosis	1/217 (0.5%)		0/215 (0%)
Thrombosis	1/217 (0.5%)		1/215 (0.5%)
Venous thrombosis	0/217 (0%)		1/215 (0.5%)
Other (Not Including Serious) Adverse Events
	Sunitinib + Capecitabine		Capecitabine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	214/217 (98.6%)		208/215 (96.7%)
Blood and lymphatic system disorders
Anaemia	53/217 (24.4%)		35/215 (16.3%)
Leukopenia	51/217 (23.5%)		19/215 (8.8%)
Neutropenia	104/217 (47.9%)		39/215 (18.1%)
Thrombocytopenia	102/217 (47%)		14/215 (6.5%)
Febrile neutropenia	2/217 (0.9%)		0/215 (0%)
Haematotoxicity	2/217 (0.9%)		0/215 (0%)
Haemorrhagic diathesis	1/217 (0.5%)		0/215 (0%)
Leukocytosis	1/217 (0.5%)		0/215 (0%)
Lymphadenopathy	1/217 (0.5%)		0/215 (0%)
Lymphocytosis	1/217 (0.5%)		0/215 (0%)
Lymphopenia	5/217 (2.3%)		0/215 (0%)
Macrocytosis	0/217 (0%)		1/215 (0.5%)
Pancytopenia	1/217 (0.5%)		0/215 (0%)
Cardiac disorders
Angina pectoris	3/217 (1.4%)		0/215 (0%)
Arrhythmia	2/217 (0.9%)		0/215 (0%)
Atrial fibrillation	0/217 (0%)		2/215 (0.9%)
Bradycardia	2/217 (0.9%)		0/215 (0%)
Cardiac disorder	1/217 (0.5%)		0/215 (0%)
Cardiovascular disorder	1/217 (0.5%)		0/215 (0%)
Cyanosis	1/217 (0.5%)		0/215 (0%)
Left ventricular dysfunction	4/217 (1.8%)		1/215 (0.5%)
Palpitations	4/217 (1.8%)		1/215 (0.5%)
Pericardial effusion	3/217 (1.4%)		1/215 (0.5%)
Pericarditis	0/217 (0%)		1/215 (0.5%)
Sinus bradycardia	1/217 (0.5%)		0/215 (0%)
Sinus tachycardia	1/217 (0.5%)		4/215 (1.9%)
Tachycardia	2/217 (0.9%)		2/215 (0.9%)
Ear and labyrinth disorders
Ear pain	4/217 (1.8%)		0/215 (0%)
Tinnitus	3/217 (1.4%)		3/215 (1.4%)
Vertigo	8/217 (3.7%)		13/215 (6%)
Endocrine disorders
Hypothyroidism	22/217 (10.1%)		2/215 (0.9%)
Hyperthyroidism	1/217 (0.5%)		0/215 (0%)
Eye disorders
Conjunctivitis	4/217 (1.8%)		16/215 (7.4%)
Lacrimation increased	23/217 (10.6%)		24/215 (11.2%)
Conjunctival haemorrhage	1/217 (0.5%)		0/215 (0%)
Conjunctival irritation	0/217 (0%)		1/215 (0.5%)
Diplopia	2/217 (0.9%)		0/215 (0%)
Dry eye	7/217 (3.2%)		4/215 (1.9%)
Exophthalmos	1/217 (0.5%)		0/215 (0%)
Eye disorder	1/217 (0.5%)		0/215 (0%)
Eye inflammation	1/217 (0.5%)		0/215 (0%)
Eye irritation	5/217 (2.3%)		7/215 (3.3%)
Eye oedema	2/217 (0.9%)		2/215 (0.9%)
Eye pain	2/217 (0.9%)		1/215 (0.5%)
Eye swelling	1/217 (0.5%)		0/215 (0%)
Eyelash discolouration	2/217 (0.9%)		0/215 (0%)
Eyelid oedema	5/217 (2.3%)		0/215 (0%)
Eyelid ptosis	1/217 (0.5%)		1/215 (0.5%)
Keratitis	1/217 (0.5%)		0/215 (0%)
Mydriasis	0/217 (0%)		1/215 (0.5%)
Ocular discomfort	0/217 (0%)		1/215 (0.5%)
Ocular hyperaemia	0/217 (0%)		1/215 (0.5%)
Ocular icterus	1/217 (0.5%)		0/215 (0%)
Periorbital oedema	2/217 (0.9%)		0/215 (0%)
Photophobia	0/217 (0%)		1/215 (0.5%)
Retinal disorder	0/217 (0%)		1/215 (0.5%)
Vision blurred	1/217 (0.5%)		2/215 (0.9%)
Visual acuity reduced	1/217 (0.5%)		0/215 (0%)
Visual impairment	9/217 (4.1%)		1/215 (0.5%)
Vitreous floaters	2/217 (0.9%)		0/215 (0%)
Xerophthalmia	1/217 (0.5%)		0/215 (0%)
Abdominal distension	2/217 (0.9%)		4/215 (1.9%)
Gastrointestinal disorders
Abdominal pain	38/217 (17.5%)		29/215 (13.5%)
Abdominal pain upper	48/217 (22.1%)		30/215 (14%)
Constipation	41/217 (18.9%)		42/215 (19.5%)
Diarrhoea	121/217 (55.8%)		95/215 (44.2%)
Dry mouth	19/217 (8.8%)		16/215 (7.4%)
Dyspepsia	38/217 (17.5%)		13/215 (6%)
Dysphagia	13/217 (6%)		1/215 (0.5%)
Flatulence	13/217 (6%)		11/215 (5.1%)
Gastrooesophageal reflux disease	12/217 (5.5%)		5/215 (2.3%)
Gingivitis	11/217 (5.1%)		2/215 (0.9%)
Nausea	122/217 (56.2%)		91/215 (42.3%)
Oesophagitis	14/217 (6.5%)		2/215 (0.9%)
Stomatitis	61/217 (28.1%)		26/215 (12.1%)
Vomiting	90/217 (41.5%)		55/215 (25.6%)
Abdominal discomfort	1/217 (0.5%)		1/215 (0.5%)
Abdominal hernia	1/217 (0.5%)		0/215 (0%)
Abdominal pain lower	0/217 (0%)		1/215 (0.5%)
Abdominal rigidity	1/217 (0.5%)		2/215 (0.9%)
Anal inflammation	4/217 (1.8%)		0/215 (0%)
Anal stenosis	0/217 (0%)		1/215 (0.5%)
Anorectal discomfort	0/217 (0%)		1/215 (0.5%)
Aphthous stomatitis	8/217 (3.7%)		5/215 (2.3%)
Ascites	5/217 (2.3%)		2/215 (0.9%)
Chapped lips	0/217 (0%)		1/215 (0.5%)
Cheilitis	1/217 (0.5%)		3/215 (1.4%)
Colitis	2/217 (0.9%)		0/215 (0%)
Dental caries	1/217 (0.5%)		0/215 (0%)
Epigastric discomfort	0/217 (0%)		1/215 (0.5%)
Eructation	4/217 (1.8%)		0/215 (0%)
Faecal incontinence	1/217 (0.5%)		0/215 (0%)
Food poisoning	1/217 (0.5%)		0/215 (0%)
Gastric disorder	1/217 (0.5%)		0/215 (0%)
Gastritis	1/217 (0.5%)		1/215 (0.5%)
Gastrointestinal disorder	1/217 (0.5%)		1/215 (0.5%)
Gastrointestinal hypermotility	1/217 (0.5%)		0/215 (0%)
Gastrointestinal pain	0/217 (0%)		1/215 (0.5%)
Gingival bleeding	9/217 (4.1%)		1/215 (0.5%)
Gingival disorder	1/217 (0.5%)		0/215 (0%)
Gingival oedema	1/217 (0.5%)		0/215 (0%)
Gingival pain	4/217 (1.8%)		1/215 (0.5%)
Gingival swelling	1/217 (0.5%)		0/215 (0%)
Gingival ulceration	1/217 (0.5%)		0/215 (0%)
Glossitis	2/217 (0.9%)		0/215 (0%)
Glossodynia	6/217 (2.8%)		0/215 (0%)
Haematemesis	1/217 (0.5%)		0/215 (0%)
Haematochezia	2/217 (0.9%)		0/215 (0%)
Haemorrhoids	5/217 (2.3%)		7/215 (3.3%)
Hypoaesthesia oral	0/217 (0%)		1/215 (0.5%)
Ileitis	0/217 (0%)		1/215 (0.5%)
Irritable bowel syndrome	0/217 (0%)		1/215 (0.5%)
Lip dry	0/217 (0%)		3/215 (1.4%)
Lip haematoma	0/217 (0%)		1/215 (0.5%)
Lip pain	1/217 (0.5%)		0/215 (0%)
Loose tooth	1/217 (0.5%)		0/215 (0%)
Mouth haemorrhage	1/217 (0.5%)		0/215 (0%)
Mouth ulceration	4/217 (1.8%)		1/215 (0.5%)
Odynophagia	2/217 (0.9%)		0/215 (0%)
Oedema mouth	1/217 (0.5%)		0/215 (0%)
Oesophageal disorder	1/217 (0.5%)		1/215 (0.5%)
Oesophageal pain	1/217 (0.5%)		2/215 (0.9%)
Oral discomfort	3/217 (1.4%)		0/215 (0%)
Oral mucosal eruption	1/217 (0.5%)		0/215 (0%)
Oral mucosal erythema	0/217 (0%)		1/215 (0.5%)
Oral pain	8/217 (3.7%)		0/215 (0%)
Pancreatitis	1/217 (0.5%)		0/215 (0%)
Paraesthesia oral	1/217 (0.5%)		1/215 (0.5%)
Periodontal disease	1/217 (0.5%)		0/215 (0%)
Proctalgia	2/217 (0.9%)		0/215 (0%)
Proctitis	0/217 (0%)		1/215 (0.5%)
Rectal haemorrhage	7/217 (3.2%)		2/215 (0.9%)
Reflux oesophagitis	2/217 (0.9%)		0/215 (0%)
Sensitivity of teeth	2/217 (0.9%)		2/215 (0.9%)
Tongue discolouration	1/217 (0.5%)		1/215 (0.5%)
Tongue oedema	1/217 (0.5%)		0/215 (0%)
Tongue ulceration	1/217 (0.5%)		0/215 (0%)
Tooth disorder	0/217 (0%)		2/215 (0.9%)
Toothache	5/217 (2.3%)		2/215 (0.9%)
Umbilical hernia	1/217 (0.5%)		0/215 (0%)
General disorders
Asthenia	75/217 (34.6%)		49/215 (22.8%)
Chest pain	12/217 (5.5%)		12/215 (5.6%)
Fatigue	65/217 (30%)		53/215 (24.7%)
Mucosal inflammation	49/217 (22.6%)		24/215 (11.2%)
Oedema peripheral	16/217 (7.4%)		19/215 (8.8%)
Pain	11/217 (5.1%)		8/215 (3.7%)
Pyrexia	21/217 (9.7%)		15/215 (7%)
Axillary pain	8/217 (3.7%)		3/215 (1.4%)
Catheter site pain	0/217 (0%)		1/215 (0.5%)
Catheter site rash	1/217 (0.5%)		0/215 (0%)
Chest discomfort	2/217 (0.9%)		1/215 (0.5%)
Chills	5/217 (2.3%)		3/215 (1.4%)
Condition aggravated	1/217 (0.5%)		2/215 (0.9%)
Disease progression	1/217 (0.5%)		0/215 (0%)
Face oedema	6/217 (2.8%)		2/215 (0.9%)
Feeling abnormal	1/217 (0.5%)		0/215 (0%)
Feeling cold	2/217 (0.9%)		1/215 (0.5%)
Feeling hot	1/217 (0.5%)		0/215 (0%)
Gait disturbance	2/217 (0.9%)		0/215 (0%)
General physical health deterioration	3/217 (1.4%)		3/215 (1.4%)
Hyperthermia	3/217 (1.4%)		0/215 (0%)
Induration	1/217 (0.5%)		0/215 (0%)
Inflammation	0/217 (0%)		1/215 (0.5%)
Influenza like illness	3/217 (1.4%)		6/215 (2.8%)
Infusion site extravasation	0/217 (0%)		1/215 (0.5%)
Injection site thrombosis	0/217 (0%)		1/215 (0.5%)
Local swelling	0/217 (0%)		1/215 (0.5%)
Localised oedema	1/217 (0.5%)		0/215 (0%)
Malaise	1/217 (0.5%)		1/215 (0.5%)
Mass	0/217 (0%)		1/215 (0.5%)
Nodule	1/217 (0.5%)		1/215 (0.5%)
Oedema	4/217 (1.8%)		2/215 (0.9%)
Secretion discharge	1/217 (0.5%)		0/215 (0%)
Swelling	0/217 (0%)		1/215 (0.5%)
Temperature intolerance	1/217 (0.5%)		0/215 (0%)
Thirst	0/217 (0%)		1/215 (0.5%)
Ulcer	1/217 (0.5%)		2/215 (0.9%)
Xerosis	3/217 (1.4%)		3/215 (1.4%)
Hepatobiliary disorders
Hyperbilirubinaemia	13/217 (6%)		13/215 (6%)
Jaundice	11/217 (5.1%)		0/215 (0%)
Cholelithiasis	2/217 (0.9%)		0/215 (0%)
Hepatic failure	1/217 (0.5%)		0/215 (0%)
Hepatic function abnormal	1/217 (0.5%)		0/215 (0%)
Hepatic pain	2/217 (0.9%)		1/215 (0.5%)
Hepatomegaly	1/217 (0.5%)		1/215 (0.5%)
Hepatotoxicity	0/217 (0%)		1/215 (0.5%)
Hypertransaminasaemia	2/217 (0.9%)		0/215 (0%)
Portal vein thrombosis	0/217 (0%)		1/215 (0.5%)
Immune system disorders
Drug hypersensitivity	0/217 (0%)		1/215 (0.5%)
Hypersensitivity	0/217 (0%)		1/215 (0.5%)
Seasonal allergy	1/217 (0.5%)		2/215 (0.9%)
Infections and infestations
Nasopharyngitis	16/217 (7.4%)		10/215 (4.7%)
Rhinitis	1/217 (0.5%)		13/215 (6%)
Urinary tract infection	16/217 (7.4%)		11/215 (5.1%)
Abscess	1/217 (0.5%)		0/215 (0%)
Bronchitis	7/217 (3.2%)		7/215 (3.3%)
Bronchopneumonia	1/217 (0.5%)		0/215 (0%)
Candidiasis	1/217 (0.5%)		1/215 (0.5%)
Cellulitis	1/217 (0.5%)		3/215 (1.4%)
Clostridial infection	1/217 (0.5%)		0/215 (0%)
Conjunctivitis infective	1/217 (0.5%)		1/215 (0.5%)
Cystitis	5/217 (2.3%)		6/215 (2.8%)
Device related infection	2/217 (0.9%)		0/215 (0%)
Ear infection	1/217 (0.5%)		1/215 (0.5%)
Erysipelas	0/217 (0%)		1/215 (0.5%)
Escherichia infection	1/217 (0.5%)		0/215 (0%)
Escherichia urinary tract infection	1/217 (0.5%)		0/215 (0%)
Eye infection	0/217 (0%)		2/215 (0.9%)
Folliculitis	0/217 (0%)		1/215 (0.5%)
Gastroenteritis	1/217 (0.5%)		2/215 (0.9%)
Gastroenteritis viral	0/217 (0%)		5/215 (2.3%)
Herpes simplex	4/217 (1.8%)		3/215 (1.4%)
Herpes virus infection	1/217 (0.5%)		1/215 (0.5%)
Herpes zoster	0/217 (0%)		2/215 (0.9%)
Infected skin ulcer	0/217 (0%)		1/215 (0.5%)
Infection	2/217 (0.9%)		2/215 (0.9%)
Influenza	7/217 (3.2%)		7/215 (3.3%)
Laryngitis	3/217 (1.4%)		3/215 (1.4%)
Localised infection	1/217 (0.5%)		3/215 (1.4%)
Lower respiratory tract infection	0/217 (0%)		4/215 (1.9%)
Lung infection	1/217 (0.5%)		0/215 (0%)
Lymphangitis	0/217 (0%)		1/215 (0.5%)
Nail bed infection	1/217 (0.5%)		2/215 (0.9%)
Nail infection	0/217 (0%)		1/215 (0.5%)
Oesophageal candidiasis	2/217 (0.9%)		0/215 (0%)
Onychomycosis	0/217 (0%)		2/215 (0.9%)
Oral candidiasis	1/217 (0.5%)		3/215 (1.4%)
Oral fungal infection	1/217 (0.5%)		0/215 (0%)
Oral herpes	0/217 (0%)		3/215 (1.4%)
Oral infection	0/217 (0%)		1/215 (0.5%)
Osteomyelitis	1/217 (0.5%)		1/215 (0.5%)
Otitis media	1/217 (0.5%)		0/215 (0%)
Paronychia	0/217 (0%)		2/215 (0.9%)
Pharyngitis	4/217 (1.8%)		5/215 (2.3%)
Puncture site infection	0/217 (0%)		1/215 (0.5%)
Rectal abscess	1/217 (0.5%)		0/215 (0%)
Respiratory tract infection	1/217 (0.5%)		1/215 (0.5%)
Sinusitis	0/217 (0%)		3/215 (1.4%)
Skin infection	2/217 (0.9%)		0/215 (0%)
Subcutaneous abscess	1/217 (0.5%)		0/215 (0%)
Tinea pedis	0/217 (0%)		3/215 (1.4%)
Tooth abscess	9/217 (4.1%)		4/215 (1.9%)
Tooth infection	4/217 (1.8%)		0/215 (0%)
Tracheitis	0/217 (0%)		1/215 (0.5%)
Upper respiratory tract infection	1/217 (0.5%)		3/215 (1.4%)
Vaginal infection	2/217 (0.9%)		0/215 (0%)
Viral infection	1/217 (0.5%)		3/215 (1.4%)
Viral upper respiratory tract infection	0/217 (0%)		1/215 (0.5%)
Vulvovaginal candidiasis	3/217 (1.4%)		1/215 (0.5%)
Vulvovaginal mycotic infection	2/217 (0.9%)		1/215 (0.5%)
Vulvovaginitis	0/217 (0%)		1/215 (0.5%)
Wound infection	1/217 (0.5%)		0/215 (0%)
Injury, poisoning and procedural complications
Accidental overdose	3/217 (1.4%)		0/215 (0%)
Animal bite	0/217 (0%)		1/215 (0.5%)
Arthropod bite	1/217 (0.5%)		1/215 (0.5%)
Clavicle fracture	1/217 (0.5%)		0/215 (0%)
Contusion	1/217 (0.5%)		1/215 (0.5%)
Fall	1/217 (0.5%)		2/215 (0.9%)
Foreign body	0/217 (0%)		1/215 (0.5%)
Hand fracture	0/217 (0%)		1/215 (0.5%)
Injury	0/217 (0%)		1/215 (0.5%)
Joint injury	0/217 (0%)		1/215 (0.5%)
Joint sprain	0/217 (0%)		2/215 (0.9%)
Ligament injury	0/217 (0%)		1/215 (0.5%)
Lip injury	1/217 (0.5%)		0/215 (0%)
Open wound	1/217 (0.5%)		0/215 (0%)
Overdose	2/217 (0.9%)		0/215 (0%)
Pelvic fracture	1/217 (0.5%)		0/215 (0%)
Radius fracture	0/217 (0%)		1/215 (0.5%)
Rib fracture	0/217 (0%)		2/215 (0.9%)
Seroma	1/217 (0.5%)		0/215 (0%)
Tooth fracture	0/217 (0%)		1/215 (0.5%)
Whiplash injury	0/217 (0%)		1/215 (0.5%)
Wound	2/217 (0.9%)		2/215 (0.9%)
Wrist fracture	0/217 (0%)		1/215 (0.5%)
Investigations
Alanine aminotransferase increased	11/217 (5.1%)		15/215 (7%)
Aspartate aminotransferase increased	19/217 (8.8%)		13/215 (6%)
Blood alkaline phosphatase increased	12/217 (5.5%)		8/215 (3.7%)
Platelet count decreased	15/217 (6.9%)		4/215 (1.9%)
Weight decreased	20/217 (9.2%)		17/215 (7.9%)
Blood albumin decreased	1/217 (0.5%)		0/215 (0%)
Blood bilirubin increased	6/217 (2.8%)		3/215 (1.4%)
Blood creatinine increased	1/217 (0.5%)		0/215 (0%)
Blood glucose increased	0/217 (0%)		1/215 (0.5%)
Blood iron increased	1/217 (0.5%)		0/215 (0%)
Blood lactate dehydrogenase increased	2/217 (0.9%)		0/215 (0%)
Blood phosphorus decreased	0/217 (0%)		1/215 (0.5%)
Blood potassium decreased	2/217 (0.9%)		2/215 (0.9%)
Blood pressure decreased	0/217 (0%)		1/215 (0.5%)
Blood pressure increased	1/217 (0.5%)		0/215 (0%)
Blood thyroid stimulating hormone increased	7/217 (3.2%)		4/215 (1.9%)
Blood uric acid increased	2/217 (0.9%)		1/215 (0.5%)
Breath sounds abnormal	0/217 (0%)		2/215 (0.9%)
Creatinine renal clearance decreased	0/217 (0%)		1/215 (0.5%)
Ejection fraction decreased	8/217 (3.7%)		3/215 (1.4%)
Electrocardiogram QT prolonged	2/217 (0.9%)		0/215 (0%)
Electrocardiogram T wave abnormal	1/217 (0.5%)		0/215 (0%)
Gamma-glutamyltransferase increased	3/217 (1.4%)		1/215 (0.5%)
Haemoglobin	1/217 (0.5%)		0/215 (0%)
Haemoglobin decreased	2/217 (0.9%)		2/215 (0.9%)
Heart rate increased	0/217 (0%)		1/215 (0.5%)
Hepatic enzyme increased	1/217 (0.5%)		0/215 (0%)
Liver function test abnormal	1/217 (0.5%)		0/215 (0%)
Neutrophil count decreased	5/217 (2.3%)		1/215 (0.5%)
Protein total increased	0/217 (0%)		1/215 (0.5%)
Respiratory rate increased	0/217 (0%)		1/215 (0.5%)
Thyroid function test abnormal	1/217 (0.5%)		0/215 (0%)
Transaminases increased	2/217 (0.9%)		1/215 (0.5%)
Weight increased	2/217 (0.9%)		5/215 (2.3%)
White blood cell count decreased	7/217 (3.2%)		2/215 (0.9%)
Metabolism and nutrition disorders
Decreased appetite	67/217 (30.9%)		44/215 (20.5%)
Hypokalaemia	11/217 (5.1%)		8/215 (3.7%)
Cachexia	1/217 (0.5%)		0/215 (0%)
Dehydration	4/217 (1.8%)		8/215 (3.7%)
Diabetes mellitus	1/217 (0.5%)		0/215 (0%)
Hypercalcaemia	5/217 (2.3%)		0/215 (0%)
Hypercholesterolaemia	2/217 (0.9%)		3/215 (1.4%)
Hyperglycaemia	6/217 (2.8%)		9/215 (4.2%)
Hyperkalaemia	0/217 (0%)		1/215 (0.5%)
Hypermagnesaemia	1/217 (0.5%)		0/215 (0%)
Hyperphosphataemia	1/217 (0.5%)		0/215 (0%)
Hypertriglyceridaemia	4/217 (1.8%)		3/215 (1.4%)
Hyperuricaemia	4/217 (1.8%)		2/215 (0.9%)
Hypoalbuminaemia	1/217 (0.5%)		4/215 (1.9%)
Hypocalcaemia	5/217 (2.3%)		5/215 (2.3%)
Hypomagnesaemia	2/217 (0.9%)		4/215 (1.9%)
Hyponatraemia	1/217 (0.5%)		2/215 (0.9%)
Hypoproteinaemia	0/217 (0%)		2/215 (0.9%)
Hypovolaemia	0/217 (0%)		1/215 (0.5%)
Polydipsia	0/217 (0%)		1/215 (0.5%)
Tetany	1/217 (0.5%)		0/215 (0%)
Vitamin K deficiency	1/217 (0.5%)		0/215 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	24/217 (11.1%)		25/215 (11.6%)
Back pain	25/217 (11.5%)		23/215 (10.7%)
Bone pain	13/217 (6%)		12/215 (5.6%)
Musculoskeletal pain	13/217 (6%)		13/215 (6%)
Myalgia	19/217 (8.8%)		7/215 (3.3%)
Pain in extremity	25/217 (11.5%)		33/215 (15.3%)
Bone disorder	0/217 (0%)		1/215 (0.5%)
Bone swelling	0/217 (0%)		1/215 (0.5%)
Coccydynia	0/217 (0%)		1/215 (0.5%)
Costochondritis	0/217 (0%)		1/215 (0.5%)
Fistula	1/217 (0.5%)		0/215 (0%)
Flank pain	2/217 (0.9%)		1/215 (0.5%)
Groin pain	1/217 (0.5%)		0/215 (0%)
Hypercreatinaemia	4/217 (1.8%)		3/215 (1.4%)
Joint lock	1/217 (0.5%)		0/215 (0%)
Joint range of motion decreased	0/217 (0%)		1/215 (0.5%)
Joint stiffness	1/217 (0.5%)		0/215 (0%)
Joint swelling	0/217 (0%)		1/215 (0.5%)
Mobility decreased	0/217 (0%)		2/215 (0.9%)
Muscle spasms	3/217 (1.4%)		10/215 (4.7%)
Muscular weakness	5/217 (2.3%)		3/215 (1.4%)
Musculoskeletal chest pain	8/217 (3.7%)		7/215 (3.3%)
Musculoskeletal stiffness	3/217 (1.4%)		1/215 (0.5%)
Neck pain	10/217 (4.6%)		10/215 (4.7%)
Osteoarthritis	0/217 (0%)		1/215 (0.5%)
Osteonecrosis	1/217 (0.5%)		0/215 (0%)
Osteonecrosis of jaw	1/217 (0.5%)		0/215 (0%)
Pain in jaw	2/217 (0.9%)		2/215 (0.9%)
Tendon disorder	1/217 (0.5%)		0/215 (0%)
Tendonitis	1/217 (0.5%)		2/215 (0.9%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Fibroma	1/217 (0.5%)		0/215 (0%)
Infected neoplasm	0/217 (0%)		1/215 (0.5%)
Malignant pleural effusion	1/217 (0.5%)		0/215 (0%)
Skin neoplasm bleeding	0/217 (0%)		1/215 (0.5%)
Thyroid neoplasm	0/217 (0%)		1/215 (0.5%)
Tumour pain	3/217 (1.4%)		2/215 (0.9%)
Tumour ulceration	1/217 (0.5%)		0/215 (0%)
Uterine leiomyoma	0/217 (0%)		1/215 (0.5%)
Nervous system disorders
Dizziness	14/217 (6.5%)		9/215 (4.2%)
Dysgeusia	58/217 (26.7%)		18/215 (8.4%)
Headache	57/217 (26.3%)		32/215 (14.9%)
Neuropathy peripheral	9/217 (4.1%)		13/215 (6%)
Paraesthesia	15/217 (6.9%)		16/215 (7.4%)
Peripheral sensory neuropathy	16/217 (7.4%)		6/215 (2.8%)
Balance disorder	2/217 (0.9%)		0/215 (0%)
Burning sensation	2/217 (0.9%)		0/215 (0%)
Cervical root pain	0/217 (0%)		1/215 (0.5%)
Cognitive disorder	1/217 (0.5%)		1/215 (0.5%)
Coma	1/217 (0.5%)		0/215 (0%)
Convulsion	1/217 (0.5%)		0/215 (0%)
Coordination abnormal	1/217 (0.5%)		0/215 (0%)
Dysaesthesia	8/217 (3.7%)		8/215 (3.7%)
Formication	0/217 (0%)		1/215 (0.5%)
Hemiparesis	0/217 (0%)		1/215 (0.5%)
Hyperaesthesia	2/217 (0.9%)		0/215 (0%)
Hypersomnia	0/217 (0%)		2/215 (0.9%)
Hypoaesthesia	4/217 (1.8%)		6/215 (2.8%)
Hypogeusia	1/217 (0.5%)		0/215 (0%)
Hypokinesia	1/217 (0.5%)		0/215 (0%)
Lethargy	1/217 (0.5%)		0/215 (0%)
Memory impairment	2/217 (0.9%)		4/215 (1.9%)
Migraine	4/217 (1.8%)		2/215 (0.9%)
Neuralgia	1/217 (0.5%)		2/215 (0.9%)
Neurotoxicity	1/217 (0.5%)		0/215 (0%)
Paresis	1/217 (0.5%)		0/215 (0%)
Peripheral motor neuropathy	3/217 (1.4%)		2/215 (0.9%)
Polyneuropathy	3/217 (1.4%)		3/215 (1.4%)
Presyncope	1/217 (0.5%)		1/215 (0.5%)
Radicular syndrome	1/217 (0.5%)		0/215 (0%)
Radiculitis lumbosacral	0/217 (0%)		1/215 (0.5%)
Sciatica	0/217 (0%)		4/215 (1.9%)
Sensory disturbance	0/217 (0%)		1/215 (0.5%)
Sensory loss	0/217 (0%)		1/215 (0.5%)
Somnolence	9/217 (4.1%)		2/215 (0.9%)
Speech disorder	2/217 (0.9%)		0/215 (0%)
Syncope	2/217 (0.9%)		0/215 (0%)
Transient ischaemic attack	1/217 (0.5%)		0/215 (0%)
Tremor	1/217 (0.5%)		2/215 (0.9%)
Trigeminal nerve disorder	0/217 (0%)		1/215 (0.5%)
VIIth nerve paralysis	1/217 (0.5%)		0/215 (0%)
VIth nerve paralysis	0/217 (0%)		1/215 (0.5%)
Psychiatric disorders
Anxiety	14/217 (6.5%)		10/215 (4.7%)
Insomnia	18/217 (8.3%)		20/215 (9.3%)
Apathy	1/217 (0.5%)		0/215 (0%)
Confusional state	4/217 (1.8%)		2/215 (0.9%)
Delirium	1/217 (0.5%)		0/215 (0%)
Depressed mood	2/217 (0.9%)		0/215 (0%)
Depression	4/217 (1.8%)		4/215 (1.9%)
Disorientation	1/217 (0.5%)		0/215 (0%)
Emotional disorder	0/217 (0%)		1/215 (0.5%)
Emotional distress	1/217 (0.5%)		0/215 (0%)
Mental status changes	0/217 (0%)		1/215 (0.5%)
Mood altered	2/217 (0.9%)		0/215 (0%)
Nervousness	1/217 (0.5%)		0/215 (0%)
Restlessness	0/217 (0%)		1/215 (0.5%)
Sleep disorder	0/217 (0%)		2/215 (0.9%)
Stress	0/217 (0%)		1/215 (0.5%)
Renal and urinary disorders
Azotaemia	2/217 (0.9%)		2/215 (0.9%)
Chromaturia	4/217 (1.8%)		0/215 (0%)
Dysuria	6/217 (2.8%)		3/215 (1.4%)
Haematuria	3/217 (1.4%)		0/215 (0%)
Hydronephrosis	1/217 (0.5%)		1/215 (0.5%)
Micturition urgency	1/217 (0.5%)		0/215 (0%)
Polyuria	1/217 (0.5%)		0/215 (0%)
Proteinuria	1/217 (0.5%)		0/215 (0%)
Renal colic	1/217 (0.5%)		1/215 (0.5%)
Renal failure	1/217 (0.5%)		2/215 (0.9%)
Renal pain	1/217 (0.5%)		0/215 (0%)
Urge incontinence	0/217 (0%)		1/215 (0.5%)
Urinary retention	1/217 (0.5%)		0/215 (0%)
Reproductive system and breast disorders
Bartholin's cyst	0/217 (0%)		1/215 (0.5%)
Breast discharge	1/217 (0.5%)		0/215 (0%)
Breast induration	1/217 (0.5%)		0/215 (0%)
Breast mass	1/217 (0.5%)		0/215 (0%)
Breast oedema	2/217 (0.9%)		0/215 (0%)
Breast pain	8/217 (3.7%)		8/215 (3.7%)
Breast swelling	0/217 (0%)		1/215 (0.5%)
Breast tenderness	2/217 (0.9%)		0/215 (0%)
Dysmenorrhoea	1/217 (0.5%)		0/215 (0%)
Endometrial hyperplasia	0/217 (0%)		1/215 (0.5%)
Menstruation irregular	1/217 (0.5%)		0/215 (0%)
Metrorrhagia	5/217 (2.3%)		1/215 (0.5%)
Ovarian cyst	0/217 (0%)		1/215 (0.5%)
Pelvic pain	1/217 (0.5%)		2/215 (0.9%)
Postmenopausal haemorrhage	0/217 (0%)		1/215 (0.5%)
Retracted nipple	0/217 (0%)		1/215 (0.5%)
Uterine haemorrhage	0/217 (0%)		1/215 (0.5%)
Vaginal haemorrhage	1/217 (0.5%)		0/215 (0%)
Vaginal inflammation	1/217 (0.5%)		0/215 (0%)
Vulvovaginal discomfort	0/217 (0%)		1/215 (0.5%)
Vulvovaginal dryness	1/217 (0.5%)		1/215 (0.5%)
Vulvovaginal pruritus	1/217 (0.5%)		1/215 (0.5%)
Respiratory, thoracic and mediastinal disorders
Cough	30/217 (13.8%)		28/215 (13%)
Dyspnoea	31/217 (14.3%)		26/215 (12.1%)
Epistaxis	31/217 (14.3%)		10/215 (4.7%)
Atelectasis	2/217 (0.9%)		0/215 (0%)
Bronchospasm	1/217 (0.5%)		1/215 (0.5%)
Chronic obstructive pulmonary disease	0/217 (0%)		1/215 (0.5%)
Dry throat	0/217 (0%)		1/215 (0.5%)
Dysphonia	5/217 (2.3%)		2/215 (0.9%)
Dyspnoea exertional	5/217 (2.3%)		6/215 (2.8%)
Emphysema	1/217 (0.5%)		0/215 (0%)
Haemoptysis	1/217 (0.5%)		0/215 (0%)
Hiccups	1/217 (0.5%)		1/215 (0.5%)
Hydrothorax	3/217 (1.4%)		1/215 (0.5%)
Hypoventilation	0/217 (0%)		1/215 (0.5%)
Hypoxia	1/217 (0.5%)		0/215 (0%)
Lung disorder	0/217 (0%)		2/215 (0.9%)
Lung infiltration	1/217 (0.5%)		0/215 (0%)
Nasal congestion	2/217 (0.9%)		0/215 (0%)
Nasal disorder	0/217 (0%)		1/215 (0.5%)
Nasal dryness	4/217 (1.8%)		4/215 (1.9%)
Nasal ulcer	1/217 (0.5%)		0/215 (0%)
Oropharyngeal blistering	1/217 (0.5%)		1/215 (0.5%)
Oropharyngeal pain	6/217 (2.8%)		4/215 (1.9%)
Orthopnoea	0/217 (0%)		1/215 (0.5%)
Painful respiration	1/217 (0.5%)		0/215 (0%)
Pleural effusion	7/217 (3.2%)		6/215 (2.8%)
Pleurisy	0/217 (0%)		1/215 (0.5%)
Pneumothorax	0/217 (0%)		1/215 (0.5%)
Productive cough	1/217 (0.5%)		1/215 (0.5%)
Pulmonary embolism	2/217 (0.9%)		3/215 (1.4%)
Pulmonary oedema	0/217 (0%)		1/215 (0.5%)
Rales	1/217 (0.5%)		0/215 (0%)
Respiration abnormal	0/217 (0%)		1/215 (0.5%)
Rhinitis allergic	0/217 (0%)		1/215 (0.5%)
Rhinorrhoea	5/217 (2.3%)		8/215 (3.7%)
Sinus disorder	1/217 (0.5%)		0/215 (0%)
Tachypnoea	0/217 (0%)		1/215 (0.5%)
Throat irritation	1/217 (0.5%)		1/215 (0.5%)
Tonsillar inflammation	0/217 (0%)		1/215 (0.5%)
Wheezing	0/217 (0%)		2/215 (0.9%)
Skin and subcutaneous tissue disorders
Alopecia	16/217 (7.4%)		12/215 (5.6%)
Dry skin	14/217 (6.5%)		16/215 (7.4%)
Erythema	15/217 (6.9%)		12/215 (5.6%)
Nail disorder	14/217 (6.5%)		19/215 (8.8%)
Palmar-plantar erythrodysaesthesia syndrome	118/217 (54.4%)		131/215 (60.9%)
Rash	18/217 (8.3%)		24/215 (11.2%)
Skin fissures	3/217 (1.4%)		12/215 (5.6%)
Acne	0/217 (0%)		1/215 (0.5%)
Angioedema	1/217 (0.5%)		0/215 (0%)
Blister	0/217 (0%)		2/215 (0.9%)
Cold sweat	1/217 (0.5%)		0/215 (0%)
Dermatitis	2/217 (0.9%)		1/215 (0.5%)
Dermatitis acneiform	0/217 (0%)		1/215 (0.5%)
Dermatitis allergic	0/217 (0%)		3/215 (1.4%)
Dermatitis contact	0/217 (0%)		1/215 (0.5%)
Ecchymosis	4/217 (1.8%)		0/215 (0%)
Eczema	3/217 (1.4%)		1/215 (0.5%)
Exfoliative rash	0/217 (0%)		2/215 (0.9%)
Hair colour changes	9/217 (4.1%)		0/215 (0%)
Hyperhidrosis	1/217 (0.5%)		0/215 (0%)
Hyperkeratosis	3/217 (1.4%)		1/215 (0.5%)
Hyperkeratosis palmaris and plantaris	0/217 (0%)		1/215 (0.5%)
Hypertrichosis	0/217 (0%)		1/215 (0.5%)
Hypoaesthesia facial	0/217 (0%)		1/215 (0.5%)
Ingrowing nail	1/217 (0.5%)		0/215 (0%)
Lipoatrophy	0/217 (0%)		1/215 (0.5%)
Macule	0/217 (0%)		1/215 (0.5%)
Madarosis	2/217 (0.9%)		0/215 (0%)
Nail dystrophy	0/217 (0%)		1/215 (0.5%)
Nail toxicity	0/217 (0%)		2/215 (0.9%)
Night sweats	1/217 (0.5%)		2/215 (0.9%)
Onychoclasis	0/217 (0%)		2/215 (0.9%)
Onycholysis	0/217 (0%)		3/215 (1.4%)
Onychomadesis	0/217 (0%)		1/215 (0.5%)
Pain of skin	0/217 (0%)		1/215 (0.5%)
Palmar erythema	1/217 (0.5%)		1/215 (0.5%)
Papule	1/217 (0.5%)		2/215 (0.9%)
Petechiae	1/217 (0.5%)		1/215 (0.5%)
Photosensitivity reaction	1/217 (0.5%)		2/215 (0.9%)
Pigmentation disorder	2/217 (0.9%)		0/215 (0%)
Plantar erythema	0/217 (0%)		2/215 (0.9%)
Pruritus	8/217 (3.7%)		7/215 (3.3%)
Purpura	2/217 (0.9%)		0/215 (0%)
Rash erythematous	0/217 (0%)		2/215 (0.9%)
Rash generalised	1/217 (0.5%)		0/215 (0%)
Rash macular	3/217 (1.4%)		1/215 (0.5%)
Rash papular	0/217 (0%)		1/215 (0.5%)
Rash pruritic	1/217 (0.5%)		1/215 (0.5%)
Scab	0/217 (0%)		1/215 (0.5%)
Scar pain	1/217 (0.5%)		1/215 (0.5%)
Skin chapped	0/217 (0%)		1/215 (0.5%)
Skin depigmentation	1/217 (0.5%)		0/215 (0%)
Skin discolouration	7/217 (3.2%)		2/215 (0.9%)
Skin exfoliation	6/217 (2.8%)		3/215 (1.4%)
Skin hyperpigmentation	2/217 (0.9%)		3/215 (1.4%)
Skin hypopigmentation	1/217 (0.5%)		0/215 (0%)
Skin lesion	2/217 (0.9%)		0/215 (0%)
Skin odour abnormal	0/217 (0%)		1/215 (0.5%)
Skin plaque	0/217 (0%)		1/215 (0.5%)
Skin reaction	1/217 (0.5%)		2/215 (0.9%)
Skin toxicity	1/217 (0.5%)		2/215 (0.9%)
Skin ulcer	2/217 (0.9%)		1/215 (0.5%)
Stasis dermatitis	0/217 (0%)		1/215 (0.5%)
Subcutaneous nodule	1/217 (0.5%)		0/215 (0%)
Swelling face	1/217 (0.5%)		0/215 (0%)
Urticaria	2/217 (0.9%)		1/215 (0.5%)
Xeroderma	1/217 (0.5%)		0/215 (0%)
Yellow skin	9/217 (4.1%)		0/215 (0%)
Social circumstances
Inadequate diet	1/217 (0.5%)		0/215 (0%)
Surgical and medical procedures
Breast reconstruction	0/217 (0%)		1/215 (0.5%)
Tooth extraction	1/217 (0.5%)		1/215 (0.5%)
Vascular disorders
Hot flush	11/217 (5.1%)		6/215 (2.8%)
Hypertension	46/217 (21.2%)		8/215 (3.7%)
Capillary fragility	1/217 (0.5%)		0/215 (0%)
Circulatory collapse	1/217 (0.5%)		0/215 (0%)
Deep vein thrombosis	2/217 (0.9%)		4/215 (1.9%)
Flushing	0/217 (0%)		1/215 (0.5%)
Haematoma	6/217 (2.8%)		0/215 (0%)
Hyperaemia	2/217 (0.9%)		0/215 (0%)
Hypotension	1/217 (0.5%)		9/215 (4.2%)
Intermittent claudication	1/217 (0.5%)		0/215 (0%)
Lymphoedema	3/217 (1.4%)		10/215 (4.7%)
Orthostatic hypotension	1/217 (0.5%)		0/215 (0%)
Pallor	1/217 (0.5%)		3/215 (1.4%)
Phlebitis	1/217 (0.5%)		2/215 (0.9%)
Superior vena cava syndrome	1/217 (0.5%)		0/215 (0%)
Thrombosis	2/217 (0.9%)		0/215 (0%)
Trousseau's syndrome	1/217 (0.5%)		1/215 (0.5%)
Vasoconstriction	1/217 (0.5%)		0/215 (0%)
Venous insufficiency	0/217 (0%)		1/215 (0.5%)
Venous thrombosis limb	0/217 (0%)		1/215 (0.5%)

Limitations/Caveats

[Not Specified]

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.