Chemotherapy and Lapatinib or Trastuzumab in Treating Women With HER2/Neu-Positive Metastatic Breast Cancer

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00667251
• Collaborator: NCIC Clinical Trials Group (Other)
• Enrollment: 652
• Locations: 258
• Arms: 2
• Actual Duration (Months): 165.6
• Patients Per Site: 2.5
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

RATIONALE: HER2/neu is a receptor (protein) which is found in unusually high amounts in approximately 1 in 5 cancer patients. Scientific evidence suggests that having high amounts of the HER2/neu receptor is important for breast cancer to grow and spread. Women with previously untreated metastatic breast cancer (breast cancer that has spread to other organs) and with high levels of the HER2/neu receptor receive as their usual treatment chemotherapy with one of the approved chemotherapy drugs paclitaxel or docetaxel (called "taxanes") together with another approved drug called "trastuzumab". Chemotherapy drugs, such as paclitaxel and docetaxel, work either by killing tumour cells or by stopping them from dividing. Trastuzumab is an antibody that is given through a vein in the arm and it works by specifically "targeting" the HER2/neu i.e. it attaches to it and "turns it off". Although some of the patients who receive this taxane plus trastuzumab treatment feel better for some months, the cancer usually starts to grow again. Lapatinib is a new drug. Like trastuzumab, it also works by specifically "targeting" the HER2/neu receptor, but it does so in a different way. Lapatinib is not an antibody. It is a pill that is taken daily by mouth. Because lapatinib works in a different way than trastuzumab, it may be worse, as good as or better than trastuzumab in keeping metastatic HER/neu positive cancer from growing. However, this is not known.

Purpose: This randomized Phase III trial is comparing chemotherapy (a taxane) given together with lapatinib with chemotherapy (a taxane) given together with trastuzumab in women with HER2/neu positive breast cancer.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer	Biological: trastuzumab; Drug: docetaxel; Drug: lapatinib ditosylate; Drug: paclitaxel	Phase 3

Detailed Description

OBJECTIVES:

Primary

• To compare the progression-free survival of women with HER2/neu-positive metastatic breast cancer treated with taxane-based chemotherapy in combination with lapatinib ditosylate or trastuzumab (Herceptin®).

Secondary

• To compare the overall survival.

• To compare the time to CNS metastases at the time of first progression.

• To compare the incidence rates of CNS metastases at the time of progression.

• To compare the overall objective response rate (complete or partial response), time to response, and duration of response in patients with measurable disease at baseline.

• To compare the clinical benefit response rate.

• To compare the adverse event profile.

• To compare the quality of life.

• To compare clinical outcomes using biomarker changes in biological samples.

• To compare health economics, including healthcare utilization and health utilities.

OUTLINE: This is a multicenter study. Patients are stratified according to prior neoadjuvant/adjuvant anti-HER2/neu-targeted therapy (yes vs no), prior neoadjuvant/adjuvant taxane chemotherapy (yes vs no), planned taxane therapy (paclitaxel vs docetaxel), and liver metastasis (yes vs no). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive either paclitaxel IV on days 1, 8, and 15; treatment with paclitaxel repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity. Alternatively, patients may receive docetaxel IV on day 1; treatment with docetaxel repeats every 3 weeks for 8 courses in the absence of disease progression or unacceptable toxicity. Patients on docetaxel also receive filgrastim (G-CSF) according to institutional standard. All patients receive oral lapatinib ditosylate once daily during taxane treatment and continue after completion of taxane treatment, in the absence of disease progression or unacceptable toxicity.

• Arm II: Patients receive paclitaxel IV on days 1, 8, and 15 and trastuzumab (Herceptin®) IV on days 1, 8, 15, and 22. Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity. Alternatively, patients may receive docetaxel IV and trastuzumab IV on day 1. Treatment repeats every 3 weeks for 8 courses in the absence of disease progression or unacceptable toxicity. After completion of taxane chemotherapy and trastuzumab, all patients receive trastuzumab alone IV once every 3 weeks in the absence of disease progression or unacceptable toxicity.

Formalin-fixed paraffin-embedded tissue samples are analyzed for ER, PgR, EGFR, CK5/6, Ki67, and other molecular biomarkers by tissue microarray and immunohistochemistry.

Patients complete quality of life questionnaires (EORTC QLQ-C30 and a Trial Specific Checklist) at baseline, every 12 weeks for 96 weeks, and then every 24 weeks until disease progression.

After completion of study treatment, patients are followed at 4 weeks post treatment, and then every 12 weeks thereafter (counting from the beginning of study therapy).

Study Design

• Study Type: Interventional
• Actual Enrollment: 652 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized, Open-Label, Phase III Study of Taxane Based Chemotherapy With Lapatinib or Trastuzumab as First-Line Therapy for Women With HER2/Neu Positive Metastatic Breast Cancer
• Actual Study Start Date: Oct 7, 2008
• Actual Primary Completion Date: Aug 1, 2012
• Actual Study Completion Date: Jul 27, 2022

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Lapatinib Plus taxane based chemotherapy	Drug: docetaxel; 75mg/m2 IV q 3 weekly, day 1 of a 3 week cycle for 8 cycles plus G-CSF (when given together with lapatinib).; Drug: lapatinib ditosylate; 1250 mg po daily (while given with taxane). 1500mg PO daily (when given alone after taxane completion).; Drug: paclitaxel; 80mg/m2 IV q weekly days 1, 8 and 15 of a 4-week cycle for 6 cycles.
Active Comparator: Trastuzumab Plus taxane based chemotherapy.	Biological: trastuzumab; IV q weekly (loading dose 4mg/kg; subsequent doses 2mg/kg) or IV q 3 weekly (loading dose 8mg/kg, subsequent doses 6mg/kg).; Drug: docetaxel; 75mg/m2 IV q 3 weekly, day 1 of a 3 week cycle for 8 cycles plus G-CSF (when given together with lapatinib).; Drug: paclitaxel; 80mg/m2 IV q weekly days 1, 8 and 15 of a 4-week cycle for 6 cycles.

Outcome Measures

Primary Outcome Measures

1. Progression-free Survival [From randomization to RECIST V 1.0 progression or death assessed up to 39 months.]

   Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions

Secondary Outcome Measures

1. Overall Survival [From randomization to death from any cause, assessed up to 44 months.]

   OS median follow-up not achieved; estimated with quartile estimates

2. Time to CNS Metastases at the Time of First Progression [From randomization to CNS metastases at time of first progression, assessed up to 39 months.]

3. CNS Metastases at the Time of Progression (ITT) [Incidence rate of CNS metastases at first progression assessed up to 39 months]

4. CNS Metastases at the Time of Progression (HER2+) [Incidence rate of CNS mestastes at first progression, assessed up to 39 months]

5. Overall Objective Response Rate (Complete or Partial) ITT [4 years]

   Patients included in this assessment must have had at least one measurable lesion at baseline, and had at least one RECIST re-evaluation after baseline while on protocol therapy, prior to, or on, date of progression. Best overall response was classified to be Complete Response (CR) or Partial Response (PR).

6. Overall Objective Response Rate (Complete or Partial) HER2/Neu+ [Median follow-up of 21.5 months.]

   Response determined by RECIST V 1.0

7. Clinical Benefit Response Rate (ITT) [24 weeks]

   Best overall response of CR, PR or stable disease at end of week 24.

8. Clinical Benefit Response Rate (HER2/Neu+)) [24 weeks]

   Best overall response of CR, PR, or stable disease at end of week 24.

9. Quality of Life as Measured by the EORTC QLQ-C30 Global Score From Baseline to 12 Weeks [12 weeks]

   The EORTC QLQ-C30 is a questionnaire developed to assess the quality of life of cancer patients. The global score ranges from 0-100, with higher values representing a better quality of life. At 12 weeks: Group mean difference between arms

10. Effects of Changes in Biomarkers on Clinical Outcomes [Not available at this time]

11. Economic Evaluation, Including Health Utilities, as Measured by the EQ-5D Questionnaire, and Healthcare Utilization [Not available at this time]

Eligibility Criteria

Criteria

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

DISEASE CHARACTERISTICS:

• Histologically confirmed adenocarcinoma of the breast

• Metastatic (stage IV) disease at primary diagnosis or at relapse after curative intent therapy

• Local or central laboratory confirmedHER2/neu* overexpressing and/or amplified disease in the invasive component of the primary or metastatic lesion as defined by the following:

• 3+ overexpression (in > 30% of invasive tumor cells) by immunohistochemistry (IHC)

• 2+ or 3+ overexpression (in ≤ 30% of invasive tumor cells) by IHC AND demonstrates HER2/neu gene amplification by fluorescence in situ hybridization (FISH) or chromogenic in situ hybridization (CISH)

• HER2/neu gene amplification by FISH/CISH (> 6 HER2/neu gene copies per nucleus, or a FISH/CISH ratio [HER2 gene copies to chromosome 17 signals] of ≥ 2.2) NOTE: *Patients with a negative or equivocal overall result (FISH/CISH ratio of < 2.2, ≤ 6.0 HER2/neu gene copies per nucleus, or staining scores of 0, 1+, 2+, or 3+ [in ≤ 30% of neoplastic cells] by IHC) are not eligible

• Formalin-fixed paraffin-embedded tumor specimen available

• No CNS metastases (including leptomeningeal involvement)

• Hormone receptor status not specified

PATIENT CHARACTERISTICS:

• Menopausal status not specified

• ECOG performance status 0-2

• Life expectancy > 6 months

• Absolute granulocyte count > 1,500/mm³

• Platelet count > 75,000/mm³

• Hemoglobin > 10 g/dL

• Serum creatinine ≤ 2.0 times upper limit of normal (ULN)

• Total bilirubin ≤ 1.5 times ULN (< 3 times ULN for patients with Gilbert's disease)

• AST and/or ALT ≤ 2.5 times ULN (< 5 times ULN for patients planning to receive paclitaxel-based therapy)

• LVEF ≥ 50% by MUGA or ECHO

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• Must be accessible for study treatment and follow-up

• No history of other malignancies, except adequately treated ductal carcinoma in situ or lobular carcinoma in situ, adequately treated nonmelanoma skin cancer, curatively treated carcinoma in situ of the cervix, or other curatively treated solid tumor (non-breast) with no evidence of disease for ≥ 5 years

• No serious cardiac illness or condition including, but not limited to, any of the following:

• History of documented congestive heart failure

• Systolic dysfunction (LVEF < 50%)

• High-risk uncontrolled arrhythmias (i.e., ventricular tachycardia, high-grade atrioventricular block, or supraventricular arrhythmias that are not adequately rate-controlled)

• Unstable angina pectoris requiring anti-anginal medication

• Clinically significant valvular heart disease

• Evidence of transmural infarction on ECG

• Inadequately controlled hypertension (i.e., systolic blood pressure [BP] > 180 mm Hg or diastolic BP > 100 mm Hg)

• New York Heart Association class III-IV functional status

• No serious illness or medical condition that would not allow the patient to be managed according to the protocol including, but not limited to, any of the following:

• History of significant neurologic or psychiatric disorder that would impair the ability to obtain informed consent or limit compliance with study requirements

• Active uncontrolled infection

• Serious or nonhealing wound, ulcer, or bone fracture

• No peripheral neuropathy ≥ grade 2

• No gastrointestinal (GI) tract disease resulting in an inability to take oral medication including, but not limited to, any of the following:

• Malabsorption syndrome

• Requirement for IV alimentation

• Uncontrolled inflammatory GI disease (e.g., Crohn's disease or ulcerative colitis)

• No history of allergic or hypersensitivity reactions to any study drug or their excipients or to compounds with similar chemical composition to any of the study drugs

• Prior allergic reactions to taxanes are allowed provided they were adequately treated and, according to the treating physician, would not prohibit further treatment with taxanes

PRIOR CONCURRENT THERAPY:

• Recovered from all prior therapy

• No prior chemotherapy, immunotherapy, biological therapy, or anti-HER2/neu-targeted therapy for recurrent or metastatic breast cancer

• At least 12 months since prior chemotherapeutic agents, including taxanes, in the neoadjuvant or adjuvant setting

• At least 12 months since prior anti-HER2/neu-targeted therapy in the neoadjuvant or adjuvant setting

• Prior treatment with endocrine therapy in the neoadjuvant, adjuvant, or metastatic setting allowed

• At least 2 weeks since prior radiotherapy in the adjuvant or metastatic setting

• Prior radiotherapy to a solitary metastatic lesion allowed provided there is documented disease progression after completion of radiotherapy

• More than 30 days (or 5 half-lives) since prior investigational drugs

• At least 7 days since prior and no concurrent CYP3A4 inhibitors (6 months for amiodarone)

• At least 14 days since prior and no concurrent CYP3A4 inducers

• No prior surgical procedures affecting absorption (e.g., resection of stomach or small bowel)

• No concurrent palliative radiotherapy

• No other concurrent anticancer treatment

• No other concurrent investigational drugs for breast cancer

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Anchorage	Alaska	United States	99508
2	Novartis Investigative Site	Tucson	Arizona	United States	85715
3	Novartis Investigative Site	Hot Springs	Arkansas	United States	71913
4	Novartis Investigative Site	Berkeley	California	United States	94704
5	Novartis Investigative Site	Highland	California	United States	92346
6	Novartis Investigative Site	Montebello	California	United States	90640
7	Novartis Investigative Site	Colorado Springs	Colorado	United States	80907
8	Novartis Investigative Site	Denver	Colorado	United States	80204
9	Novartis Investigative Site	Greenwich	Connecticut	United States	06830
10	Novartis Investigative Site	Southington	Connecticut	United States	06489
11	Novartis Investigative Site	Stamford	Connecticut	United States	06902-3628
12	Novartis Investigative Site	Trumbull	Connecticut	United States	06611
13	Novartis Investigative Site	Waterbury	Connecticut	United States	06708
14	Novartis Investigative Site	Kissimmee	Florida	United States	34741
15	Novartis Investigative Site	Loxahatchee Groves	Florida	United States	33470
16	Novartis Investigative Site	New Port Richey	Florida	United States	34655
17	Novartis Investigative Site	Augusta	Georgia	United States	30901
18	Novartis Investigative Site	Lawrenceville	Georgia	United States	30046
19	Novartis Investigative Site	Savannah	Georgia	United States	31405
20	Novartis Investigative Site	Post Falls	Idaho	United States	83854
21	Novartis Investigative Site	Chicago	Illinois	United States	60657
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28	Novartis Investigative Site	Towson	Maryland	United States	21204
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32	Novartis Investigative Site	Kearney	Nebraska	United States	68845
33	Novartis Investigative Site	Kearney	Nebraska	United States	68847
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62	Novartis Investigative Site	Tucuman		Argentina	4000
63	Novartis Investigative Site	Garran	Australian Capital Territory	Australia	2606
64	Novartis Investigative Site	Liverpool	New South Wales	Australia	2170
65	Novartis Investigative Site	North Sydney	New South Wales	Australia	2060
66	Novartis Investigative Site	Tweed Heads	New South Wales	Australia	2485
67	Novartis Investigative Site	Woolloongabba	Queensland	Australia	4102
68	Novartis Investigative Site	Adelaide	South Australia	Australia	5000
69	Novartis Investigative Site	Bedford Park	South Australia	Australia	5042
70	Novartis Investigative Site	Kurralta Park	South Australia	Australia	5037
71	Novartis Investigative Site	Hobart	Tasmania	Australia	7000
72	Novartis Investigative Site	Box Hill	Victoria	Australia	3128
73	Novartis Investigative Site	Fitzroy	Victoria	Australia	3065
74	Novartis Investigative Site	Wodonga	Victoria	Australia	3690
75	Novartis Investigative Site	Subiaco	Western Australia	Australia	6008
76	Novartis Investigative Site	Gent		Belgium	9000
77	Novartis Investigative Site	Jette		Belgium	1090
78	Novartis Investigative Site	Liege		Belgium	4000
79	Novartis Investigative Site	Namur		Belgium	5000
80	Novartis Investigative Site	Edmonton	Alberta	Canada	T6G 1Z2
81	Novartis Investigative Site	Kelowna	British Columbia	Canada	V1Y 5L3
82	Novartis Investigative Site	Surrey	British Columbia	Canada	V3V 1Z2
83	Novartis Investigative Site	Vancouver	British Columbia	Canada	V5Z 4E6
84	Novartis Investigative Site	Victoria	British Columbia	Canada	V8R 6V5
85	Novartis Investigative Site	Winnipeg	Manitoba	Canada	R3E 0V9
86	Novartis Investigative Site	Moncton	New Brunswick	Canada	E1C 6Z8
87	Novartis Investigative Site	Saint John	New Brunswick	Canada	E2L 4L2
88	Novartis Investigative Site	Barrie	Ontario	Canada	L4M 6M2
89	Novartis Investigative Site	Hamilton	Ontario	Canada	L8V 5C2
90	Novartis Investigative Site	Kingston	Ontario	Canada	K7L 5P9
91	Novartis Investigative Site	London	Ontario	Canada	N6A 4L6
92	Novartis Investigative Site	Newmarket	Ontario	Canada	L3Y 2P9
93	Novartis Investigative Site	Ottawa	Ontario	Canada	K1H 8L6
94	Novartis Investigative Site	Sault Ste. Marie	Ontario	Canada	P6B 0A8
95	Novartis Investigative Site	St Catharines	Ontario	Canada	L2R 7C6
96	Novartis Investigative Site	Sudbury	Ontario	Canada	P3E 5J1
97	Novartis Investigative Site	Thunder Bay	Ontario	Canada	P7B 6V4
98	Novartis Investigative Site	Charlottetown	Prince Edward Island	Canada	C1A 8T5
99	Novartis Investigative Site	Montreal	Quebec	Canada	H1T 2M4
100	Novartis Investigative Site	Montreal	Quebec	Canada	H2L 4M1
101	Novartis Investigative Site	Montreal	Quebec	Canada	H2W 1S6
102	Novartis Investigative Site	Regina	Saskatchewan	Canada	S4T 7T1
103	Novartis Investigative Site	Saskatoon	Saskatchewan	Canada	S7N 4H4
104	Novartis Investigative Site	Quebec		Canada	G1S 4L8
105	Novartis Investigative Site	Angers		France	49033
106	Novartis Investigative Site	Bordeaux		France	33075
107	Novartis Investigative Site	Bordeaux		France	33077
108	Novartis Investigative Site	Caen Cedex 05		France	14076
109	Novartis Investigative Site	Marseille cedex 9		France	13273
110	Novartis Investigative Site	Metz-Tessy		France	74370
111	Novartis Investigative Site	Nantes cedex		France	44202
112	Novartis Investigative Site	Paris		France	75014
113	Novartis Investigative Site	Strasbourg		France	67085
114	Novartis Investigative Site	Heidelberg	Baden-Wuerttemberg	Germany	69115
115	Novartis Investigative Site	Stuttgart	Baden-Wuerttemberg	Germany	70190
116	Novartis Investigative Site	Coburg	Bayern	Germany	96450
117	Novartis Investigative Site	Eggenfelden	Bayern	Germany	84307
118	Novartis Investigative Site	Fuerth	Bayern	Germany	90766
119	Novartis Investigative Site	Regensburg	Bayern	Germany	93049
120	Novartis Investigative Site	Rosenheim	Bayern	Germany	83022
121	Novartis Investigative Site	Weiden	Bayern	Germany	92637
122	Novartis Investigative Site	Fuerstenwalde	Brandenburg	Germany	15517
123	Novartis Investigative Site	Frankfurt	Hessen	Germany	60596
124	Novartis Investigative Site	Fulda	Hessen	Germany	36043
125	Novartis Investigative Site	Lich	Hessen	Germany	35423
126	Novartis Investigative Site	Goslar	Niedersachsen	Germany	38642
127	Novartis Investigative Site	Hannover	Niedersachsen	Germany	30559
128	Novartis Investigative Site	Leer	Niedersachsen	Germany	26789
129	Novartis Investigative Site	Bielefeld	Nordrhein-Westfalen	Germany	33611
130	Novartis Investigative Site	Bonn	Nordrhein-Westfalen	Germany	53113
131	Novartis Investigative Site	Coesfeld	Nordrhein-Westfalen	Germany	48653
132	Novartis Investigative Site	Essen	Nordrhein-Westfalen	Germany	45122
133	Novartis Investigative Site	Koeln	Nordrhein-Westfalen	Germany	51067
134	Novartis Investigative Site	Porta Westfalica	Nordrhein-Westfalen	Germany	32457
135	Novartis Investigative Site	Troisdorf	Nordrhein-Westfalen	Germany	53840
136	Novartis Investigative Site	Velbert	Nordrhein-Westfalen	Germany	42551
137	Novartis Investigative Site	Witten	Nordrhein-Westfalen	Germany	58452
138	Novartis Investigative Site	Koblenz	Rheinland-Pfalz	Germany	56068
139	Novartis Investigative Site	Saarbruecken	Saarland	Germany	66113
140	Novartis Investigative Site	Halle	Sachsen-Anhalt	Germany	06120
141	Novartis Investigative Site	Dresden	Sachsen	Germany	01127
142	Novartis Investigative Site	Luebeck	Schleswig-Holstein	Germany	23538
143	Novartis Investigative Site	Berlin		Germany	10117
144	Novartis Investigative Site	Berlin		Germany	10367
145	Novartis Investigative Site	Brandenburg		Germany	14770
146	Novartis Investigative Site	Hamburg		Germany	20095
147	Novartis Investigative Site	Hamburg		Germany	22081
148	Novartis Investigative Site	Hamburg		Germany	22767
149	Novartis Investigative Site	Bangalore		India	560038
150	Novartis Investigative Site	Nagpur		India	440010
151	Novartis Investigative Site	Pune		India	411001
152	Novartis Investigative Site	Beer-Sheva		Israel	84101
153	Novartis Investigative Site	Holon		Israel	58100
154	Novartis Investigative Site	Petah-Tikva		Israel	49100
155	Novartis Investigative Site	Poriya		Israel	15208
156	Novartis Investigative Site	Ramat Gan		Israel	52621
157	Novartis Investigative Site	Aviano (pn)	Friuli-Venezia-Giulia	Italy	33081
158	Novartis Investigative Site	Roma	Lazio	Italy	00189
159	Novartis Investigative Site	Sora (FR)	Lazio	Italy	03039
160	Novartis Investigative Site	Genova	Liguria	Italy	16132
161	Novartis Investigative Site	Lecce	Puglia	Italy	73100
162	Novartis Investigative Site	Sassari	Sardegna	Italy	07100
163	Novartis Investigative Site	Prato (PO)	Toscana	Italy	59100
164	Novartis Investigative Site	Chieti		Italy	66100
165	Novartis Investigative Site	Aichi		Japan	464-8681
166	Novartis Investigative Site	Chiba		Japan	277-8577
167	Novartis Investigative Site	Ehime		Japan	791-0280
168	Novartis Investigative Site	Kagoshima		Japan	892-0833
169	Novartis Investigative Site	Kanagawa		Japan	241-8515
170	Novartis Investigative Site	Osaka		Japan	540-0006
171	Novartis Investigative Site	Osaka		Japan	565-0871
172	Novartis Investigative Site	Saitama		Japan	350-1298
173	Novartis Investigative Site	Saitama		Japan	362-0806
174	Novartis Investigative Site	Shizuoka		Japan	411-8777
175	Novartis Investigative Site	Tokyo		Japan	104-8560
176	Novartis Investigative Site	Tokyo		Japan	113-8677
177	Novartis Investigative Site	Gyeonggi-do		Korea, Republic of	10408
178	Novartis Investigative Site	Gyeonggi-do		Korea, Republic of	410-769
179	Novartis Investigative Site	Seoul		Korea, Republic of	03722
180	Novartis Investigative Site	Seoul		Korea, Republic of	110-744
181	Novartis Investigative Site	Seoul		Korea, Republic of	120-752
182	Novartis Investigative Site	Songpa-gu, Seoul		Korea, Republic of	138-736
183	Novartis Investigative Site	Cuernavaca	Morelos	Mexico	62450
184	Novartis Investigative Site	Ciudad Obregon	Sonora	Mexico	85000
185	Novartis Investigative Site	Mexico City		Mexico	CP 14080
186	Novartis Investigative Site	Amsterdam		Netherlands	1091 AC
187	Novartis Investigative Site	Delft		Netherlands	2625 AD
188	Novartis Investigative Site	Dordrecht		Netherlands	3318 AT
189	Novartis Investigative Site	Maastricht		Netherlands	6229 HX
190	Novartis Investigative Site	Gdansk		Poland	80-219
191	Novartis Investigative Site	Lodz		Poland	93-509
192	Novartis Investigative Site	Olsztyn		Poland	10-226
193	Novartis Investigative Site	Olsztyn		Poland	10-513
194	Novartis Investigative Site	Plock		Poland	09-400
195	Novartis Investigative Site	Rzeszow		Poland	35-021
196	Novartis Investigative Site	Warszawa		Poland	02-781
197	Novartis Investigative Site	Warszawa		Poland	04-125
198	Novartis Investigative Site	Arkhangelsk		Russian Federation	163045
199	Novartis Investigative Site	Ivanovo		Russian Federation	153013
200	Novartis Investigative Site	Kazan		Russian Federation	420029
201	Novartis Investigative Site	Kirov		Russian Federation	610021
202	Novartis Investigative Site	Lipetsk		Russian Federation	398005
203	Novartis Investigative Site	Moscow		Russian Federation	115 478
204	Novartis Investigative Site	Ryazan		Russian Federation	390011
205	Novartis Investigative Site	St. Petersburg		Russian Federation	197022
206	Novartis Investigative Site	St. Petersburg		Russian Federation	197758
207	Novartis Investigative Site	Stavropol		Russian Federation	355047
208	Novartis Investigative Site	Ufa,		Russian Federation	450054
209	Novartis Investigative Site	Ufa		Russian Federation	450054
210	Novartis Investigative Site	Alcorcon		Spain	28922
211	Novartis Investigative Site	Alicante		Spain	03010
212	Novartis Investigative Site	Badalona		Spain	08916
213	Novartis Investigative Site	Barcelona		Spain	08036
214	Novartis Investigative Site	Elche		Spain	03202
215	Novartis Investigative Site	Girona		Spain	17007
216	Novartis Investigative Site	Jaen		Spain	23007
217	Novartis Investigative Site	La Coruna		Spain	15009
218	Novartis Investigative Site	Lugo		Spain	27003
219	Novartis Investigative Site	Madrid		Spain	28007
220	Novartis Investigative Site	Madrid		Spain	28034
221	Novartis Investigative Site	Madrid		Spain	28040
222	Novartis Investigative Site	Majadahonda (Madrid)		Spain	28222
223	Novartis Investigative Site	Pozuelo De Alarcon (Madrid)		Spain	28223
224	Novartis Investigative Site	Sevilla		Spain	41013
225	Novartis Investigative Site	Valencia		Spain	46009
226	Novartis Investigative Site	Changhua		Taiwan	500
227	Novartis Investigative Site	Taichung		Taiwan	404
228	Novartis Investigative Site	Tainan County		Taiwan	736
229	Novartis Investigative Site	Taipei		Taiwan	100
230	Novartis Investigative Site	Taipei		Taiwan	112
231	Novartis Investigative Site	Bangkok		Thailand	10700
232	Novartis Investigative Site	Chiangmai		Thailand	50200
233	Novartis Investigative Site	Dnepropetrovsk		Ukraine	49102
234	Novartis Investigative Site	Dnipropetrovsk		Ukraine	49100
235	Novartis Investigative Site	Lviv		Ukraine	79031
236	Novartis Investigative Site	Sumy		Ukraine	40005
237	Novartis Investigative Site	Bournemouth		United Kingdom	BH7 7DW
238	Novartis Investigative Site	Brighton		United Kingdom	BN2 5BE
239	Novartis Investigative Site	Chelmsford		United Kingdom	CM1 7ET
240	Novartis Investigative Site	Cheltenham		United Kingdom	GL53 7AN
241	Novartis Investigative Site	Colchester		United Kingdom	CO3 3NB
242	Novartis Investigative Site	Cottingham, Hull		United Kingdom	HU16 5JQ
243	Novartis Investigative Site	Derby		United Kingdom	DE22 3NE
244	Novartis Investigative Site	Edmonton		United Kingdom	N18 1QX
245	Novartis Investigative Site	Guildford		United Kingdom	GU2 7XX
246	Novartis Investigative Site	Harrogate		United Kingdom	HG2 7SX
247	Novartis Investigative Site	Huddersfield		United Kingdom	HD3 3EA
248	Novartis Investigative Site	London		United Kingdom	SW3 6JJ
249	Novartis Investigative Site	Newcastle upon Tyne		United Kingdom	NE7 7DN
250	Novartis Investigative Site	Norwich		United Kingdom	NR4 7UY
251	Novartis Investigative Site	Nottingham		United Kingdom	NG5 1PB
252	Novartis Investigative Site	Oxford		United Kingdom	OX3 7LJ
253	Novartis Investigative Site	Poole, Dorset		United Kingdom	BH15 2JB
254	Novartis Investigative Site	Sheffield		United Kingdom	S10 2SJ
255	Novartis Investigative Site	Shrewsbury		United Kingdom	SY3 8XQ
256	Novartis Investigative Site	Sutton		United Kingdom	SM2 5PT
257	Novartis Investigative Site	Whitchurch, Cardiff		United Kingdom	CF14 2TL
258	Novartis Investigative Site	York		United Kingdom	YO31 8HE

Sponsors and Collaborators

• Novartis Pharmaceuticals
• NCIC Clinical Trials Group

Investigators

• Study Director: Novartis pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT00667251
• Other Study ID Numbers: 108919; CLAP016A2303; CAN-NCIC-MA31; 2007-004568-27; CDR0000594764; EGF108919
• First Posted: Apr 28, 2008
• Last Update Posted: Aug 2, 2022
• Last Verified: Jul 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Novartis Pharmaceuticals: recurrent breast cancer; HER2-positive breast cancer; stage IV breast cancer
• Additional relevant MeSH terms: Breast Neoplasms; Paclitaxel; Docetaxel; Trastuzumab; Lapatinib

Study Results

Participant Flow

Arm/Group Title	Lapatinib	Trastuzumab
Arm/Group Description	Lapatinib - 1250 mg po daily Taxane based chemotherapy: Paclitaxel - 80 mg/m2 IV q weekly (days 1, 8 and 15 of a 4-week cycle) or Docetaxel - 75 mg/m2 IV q 3 weekly (day 1 of a 3-week cycle) plus G-CSF - according to institutional standards. Followed by: Lapatinib - 1500 mg po daily until disease progression.	Trastuzumab ng- IV weekly (loading dose 4 mg/kg, subsequent doses 2 mg/kg) Paclitaxel - 80 mg/m2 IV weekly (days 1, 8 and 15 of a 4-week cycle). or Trastuzumab - IV weekly (loading dose 8 mg/kg, subsequent doses 6 mg/kg) Docetaxel - 75 mg/m2 IV q 3 weekly (day 1 of a 3 week cycle) Followed by: Trastuzumab - 6 mg/kg IV q 3 weekly until disease progression.
Period Title: Overall Study
STARTED	326	326
Combination Rx	322	325
Monotherapy	225	232
Not Started	4	1
COMPLETED	256	231
NOT COMPLETED	70	95

Baseline Characteristics

Arm/Group Title	Lapatinib	Trastuzumab	Total
Arm/Group Description	Total of all reporting groups
Overall Participants	326	326	652
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	260 79.8%	263 80.7%	523 80.2%
>=65 years	66 20.2%	63 19.3%	129 19.8%
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	55.4 (26.6-87.1)	54.4 (29.3-84.3)	54.9
Sex: Female, Male (Count of Participants)
Female	326 100%	326 100%	652 100%
Male	0 0%	0 0%	0 0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	34 10.4%	34 10.4%	68 10.4%
Not Hispanic or Latino	288 88.3%	283 86.8%	571 87.6%
Unknown or Not Reported	4 1.2%	9 2.8%	13 2%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	4 1.2%	4 1.2%	8 1.2%
Asian	67 20.6%	74 22.7%	141 21.6%
Native Hawaiian or Other Pacific Islander	1 0.3%	0 0%	1 0.2%
Black or African American	5 1.5%	8 2.5%	13 2%
White	246 75.5%	234 71.8%	480 73.6%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	3 0.9%	6 1.8%	9 1.4%
Region of Enrollment (Number) [Number]
United States	10 3.1%	13 4%	23 3.5%
Taiwan	11 3.4%	11 3.4%	22 3.4%
Thailand	9 2.8%	12 3.7%	21 3.2%
Spain	19 5.8%	19 5.8%	38 5.8%
Ukraine	4 1.2%	4 1.2%	8 1.2%
Russian Federation	55 16.9%	46 14.1%	101 15.5%
Israel	16 4.9%	15 4.6%	31 4.8%
United Kingdom	33 10.1%	32 9.8%	65 10%
Italy	5 1.5%	8 2.5%	13 2%
India	4 1.2%	4 1.2%	8 1.2%
France	5 1.5%	5 1.5%	10 1.5%
Mexico	3 0.9%	6 1.8%	9 1.4%
Canada	39 12%	36 11%	75 11.5%
Argentina	8 2.5%	4 1.2%	12 1.8%
Poland	7 2.1%	12 3.7%	19 2.9%
Belgium	3 0.9%	6 1.8%	9 1.4%
Australia	17 5.2%	13 4%	30 4.6%
Netherlands	7 2.1%	7 2.1%	14 2.1%
Germany	32 9.8%	34 10.4%	66 10.1%
Japan	22 6.7%	20 6.1%	42 6.4%
Korea, Republic of	17 5.2%	19 5.8%	36 5.5%
Performance Status (Count of Participants)
ECOG 0	196 60.1%	204 62.6%	400 61.3%
ECOG 1	118 36.2%	112 34.4%	230 35.3%
ECOG 2	12 3.7%	10 3.1%	22 3.4%
Prior (Neo) Adjuvant Anti-HER2/neu Targeted Therapy (Count of Participants)
Yes	59 18.1%	59 18.1%	118 18.1%
No	267 81.9%	267 81.9%	534 81.9%
Prior (Neo) Adjuvant Taxane Chemotherapy (Count of Participants)
Yes	65 19.9%	69 21.2%	134 20.6%
No	261 80.1%	257 78.8%	518 79.4%
Prior (Neo) Adjuvant Anthracyclines (Count of Participants)
Yes	128 39.3%	140 42.9%	268 41.1%
No	198 60.7%	186 57.1%	384 58.9%
Prior (Neo) Adjuvant Other Chemotherapy (Count of Participants)
Yes	146 44.8%	161 49.4%	307 47.1%
No	180 55.2%	165 50.6%	345 52.9%
Disease Status (Count of Participants)
Primary Diagnosis	138 42.3%	138 42.3%	276 42.3%
Metastatic Relapse	187 57.4%	187 57.4%	374 57.4%
Missing	1 0.3%	1 0.3%	2 0.3%
Prior (Neo) Adjuvant/Metastatic Endocrine Therapy (Count of Participants)
Yes	122 37.4%	127 39%	249 38.2%
No	204 62.6%	198 60.7%	402 61.7%
Missing	0 0%	1 0.3%	1 0.2%
Prior (Neo) Adjuvant/Metastatic Radiotherapy (Count of Participants)
Yes	138 42.3%	149 45.7%	287 44%
No	187 57.4%	176 54%	363 55.7%
Missing	1 0.3%	1 0.3%	2 0.3%
Planned Taxane Therapy (Count of Participants)
Weekly Paclitaxel	146 44.8%	146 44.8%	292 44.8%
3-Weekly Docetaxel	180 55.2%	180 55.2%	360 55.2%
Prior (Neo) Adjuvant Other Therapy (Count of Participants)
Yes	5 1.5%	2 0.6%	7 1.1%
No	321 98.5%	323 99.1%	644 98.8%
Missing	0 0%	1 0.3%	1 0.2%
Liver Metastasis (Count of Participants)
Yes	149 45.7%	150 46%	299 45.9%
No	177 54.3%	176 54%	353 54.1%
Central Review HER2/Neu Status (Count of Participants)
Positive IHC or FISH	270 82.8%	267 81.9%	537 82.4%
Negative IHC and FISH	36 11%	46 14.1%	82 12.6%
Equivocal IHC and FISH	9 2.8%	5 1.5%	14 2.1%
Unknown	11 3.4%	8 2.5%	19 2.9%
Central Review ER Status (Count of Participants)
Positive (>0)	213 65.3%	208 63.8%	421 64.6%
Negative	96 29.4%	107 32.8%	203 31.1%
Missing	17 5.2%	11 3.4%	28 4.3%
Central Review PR Status (Count of Participants)
Positive (>0)	116 35.6%	104 31.9%	220 33.7%
Negative	190 58.3%	204 62.6%	394 60.4%
Missing	20 6.1%	18 5.5%	38 5.8%
Central Review ki67 (% cells positive) [Geometric Mean (Full Range) ]
Geometric Mean (Full Range) [% cells positive]	33.33	31.43	32.37
Central Review CK5 Status (Count of Participants)
Positive (>0)	58 17.8%	41 12.6%	99 15.2%
Negative	210 64.4%	218 66.9%	428 65.6%
Missing	58 17.8%	67 20.6%	125 19.2%
Central Review EGFR Status (Count of Participants)
Positive (>0)	71 21.8%	77 23.6%	148 22.7%
Negative	194 59.5%	181 55.5%	375 57.5%
Missing	61 18.7%	68 20.9%	129 19.8%

Outcome Measures

1. Primary Outcome

Title	Progression-free Survival
Description	Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions
Time Frame	From randomization to RECIST V 1.0 progression or death assessed up to 39 months.

Outcome Measure Data

Analysis Population Description

two subpopulations: ITT (n=652) and HER2+ (n=537)

Arm/Group Title	Lapatinib	Trastuzumab
Arm/Group Description	Plus taxane based chemotherapy	Plus taxane based chemotherapy.
Measure Participants	326	326
ITT n=326, 326	8.97	11.30
HER2+n=270, 267	9.13	13.63

2. Secondary Outcome

Title	Overall Survival
Description	OS median follow-up not achieved; estimated with quartile estimates
Time Frame	From randomization to death from any cause, assessed up to 44 months.

Outcome Measure Data

Analysis Population Description

two subpopulations: ITT (n=652) and HER2+ (n=537)

Arm/Group Title	Lapatinib	Trastuzumab
Arm/Group Description	Plus taxane based chemotherapy	Plus taxane based chemotherapy.
Measure Participants	326	326
Median (Inter-Quartile Range) [Months]	20.8	21.8

3. Secondary Outcome

Title	Time to CNS Metastases at the Time of First Progression
Time Frame	From randomization to CNS metastases at time of first progression, assessed up to 39 months.

Outcome Measure Data

Analysis Population Description

two subpopulations: ITT (n=652) and HER2+ (n=537)

Arm/Group Title	Lapatinib	Trastuzumab
Arm/Group Description	Plus taxane based chemotherapy	Plus taxane based chemotherapy.
Measure Participants	326	326
ITT n=326, 326	8.77	11.10
HER2+n=270, 267	9.03	13.17

4. Secondary Outcome

Title	CNS Metastases at the Time of Progression (ITT)
Time Frame	Incidence rate of CNS metastases at first progression assessed up to 39 months

Outcome Measure Data

Analysis Population Description

178 Lapatinib patients with metastases assessed for CNS metastases; 157 Trastuzumab patients with metastases assessed for CNS metastases.

Arm/Group Title	Lapatinib	Trastuzumab
Arm/Group Description	Plus taxane based chemotherapy	Plus taxane based chemotherapy.
Measure Participants	178	157
Number [CNS metastases]	44	52

5. Secondary Outcome

Title	CNS Metastases at the Time of Progression (HER2+)
Time Frame	Incidence rate of CNS mestastes at first progression, assessed up to 39 months

Outcome Measure Data

Analysis Population Description

151 patients with metastases assessed for CNS metastases; 128 patients with metastases assessed for CNS metastases.

Arm/Group Title	Lapatinib	Trastuzumab
Arm/Group Description	Plus taxane based chemotherapy	Plus taxane based chemotherapy.
Measure Participants	151	128
Number [CNS metastases]	40	48

6. Secondary Outcome

Title	Overall Objective Response Rate (Complete or Partial) ITT
Description	Patients included in this assessment must have had at least one measurable lesion at baseline, and had at least one RECIST re-evaluation after baseline while on protocol therapy, prior to, or on, date of progression. Best overall response was classified to be Complete Response (CR) or Partial Response (PR).
Time Frame	4 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lapatinib	Trastuzumab
Arm/Group Description	Plus taxane based chemotherapy	Plus taxane based chemotherapy.
Measure Participants	257	270
Number [Participants]	139 42.6%	148 45.4%

7. Secondary Outcome

Title	Overall Objective Response Rate (Complete or Partial) HER2/Neu+
Description	Response determined by RECIST V 1.0
Time Frame	Median follow-up of 21.5 months.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lapatinib	Trastuzumab
Arm/Group Description	Plus taxane based chemotherapy	Plus taxane based chemotherapy.
Measure Participants	216	224
Number [Participants]	121 37.1%	130 39.9%

8. Secondary Outcome

Title	Clinical Benefit Response Rate (ITT)
Description	Best overall response of CR, PR or stable disease at end of week 24.
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lapatinib	Trastuzumab
Arm/Group Description	Plus taxane based chemotherapy	Plus taxane based chemotherapy.
Measure Participants	289	303
Number [Participants]	219 67.2%	230 70.6%

9. Secondary Outcome

Title	Clinical Benefit Response Rate (HER2/Neu+))
Description	Best overall response of CR, PR, or stable disease at end of week 24.
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lapatinib	Trastuzumab
Arm/Group Description	Plus taxane based chemotherapy	Plus taxane based chemotherapy.
Measure Participants	238	251
Number [Participants]	180 55.2%	195 59.8%

10. Secondary Outcome

Title	Quality of Life as Measured by the EORTC QLQ-C30 Global Score From Baseline to 12 Weeks
Description	The EORTC QLQ-C30 is a questionnaire developed to assess the quality of life of cancer patients. The global score ranges from 0-100, with higher values representing a better quality of life. At 12 weeks: Group mean difference between arms
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lapatinib	Trastuzumab
Arm/Group Description	Plus taxane based chemotherapy	Plus taxane based chemotherapy.
Measure Participants	260	266
Mean (Standard Deviation) [Score on global scale]	61.67 (20.93)	64.41 (20.18)

11. Secondary Outcome

Title	Effects of Changes in Biomarkers on Clinical Outcomes
Time Frame	Not available at this time

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

12. Secondary Outcome

Title	Economic Evaluation, Including Health Utilities, as Measured by the EQ-5D Questionnaire, and Healthcare Utilization
Time Frame	Not available at this time

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	Median follow-up of 21.5 months
Adverse Event Reporting Description	Serious Adverse Events that were reported to Health Canada
Arm/Group Title	Lapatinib		Trastuzumab
Arm/Group Description	Plus taxane based chemotherapy		Plus taxane based chemotherapy.
All Cause Mortality
	Lapatinib		Trastuzumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Lapatinib		Trastuzumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/322 (0.9%)		0/325 (0%)
Blood and lymphatic system disorders
Hemorrhage	1/322 (0.3%)	1	0/325 (0%)	0
General disorders
Sudden Death	1/322 (0.3%)	1	0/325 (0%)	0
Respiratory, thoracic and mediastinal disorders
Colitis	1/322 (0.3%)	1	0/325 (0%)	0
Other (Not Including Serious) Adverse Events
	Lapatinib		Trastuzumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	315/322 (97.8%)		322/325 (99.1%)
Blood and lymphatic system disorders
Hemorrhage pulmonary - Nose	59/322 (18.3%)		41/325 (12.6%)
Edema: head and neck	17/322 (5.3%)		10/325 (3.1%)
Edema: Limb	81/322 (25.2%)		107/325 (32.9%)
Cardiac disorders
Hypertension	18/322 (5.6%)		26/325 (8%)
Hypertension	14/322 (4.3%)		24/325 (7.4%)
Left Ventricular Systolic Dysfunction	8/322 (2.5%)		16/325 (4.9%)
Endocrine disorders
Hot Flashes	24/322 (7.5%)		27/325 (8.3%)
Eye disorders
Blurred Vision	15/322 (4.7%)		13/325 (4%)
Watery Eye	26/322 (8.1%)		34/325 (10.5%)
Gastrointestinal disorders
Anorexia	100/322 (31.1%)		67/325 (20.6%)
Constipation	69/322 (21.4%)		85/325 (26.2%)
Diarrhea	254/322 (78.9%)		126/325 (38.8%)
Distention	18/322 (5.6%)		7/325 (2.2%)
Dry Mouth	19/322 (5.9%)		12/325 (3.7%)
Heartburn	62/322 (19.3%)		56/325 (17.2%)
Hemmorroids	15/322 (4.7%)		3/325 (0.9%)
Mucositis (clinical exam)	130/322 (40.4%)		100/325 (30.8%)
Nausea	153/322 (47.5%)		135/325 (41.5%)
Taste Alteration	54/322 (16.8%)		50/325 (15.4%)
Vomiting	96/322 (29.8%)		65/325 (20%)
Pain Abdomen NOS	45/322 (14%)		30/325 (9.2%)
Pain - stomach	16/322 (5%)		12/325 (3.7%)
Pain - throat/pharynx/larynx	12/322 (3.7%)		26/325 (8%)
Mucositis (clinical exam)-oral cavity	19/322 (5.9%)		17/325 (5.2%)
General disorders
Fatigue	221/322 (68.6%)		206/325 (63.4%)
Fever	49/322 (15.2%)		57/325 (17.5%)
Insomnia	61/322 (18.9%)		67/325 (20.6%)
Rigors/Chills	9/322 (2.8%)		19/325 (5.8%)
Weight Gain	5/322 (1.6%)		17/325 (5.2%)
Weight Loss	26/322 (8.1%)		11/325 (3.4%)
Flu-like Syndrome	17/322 (5.3%)		19/325 (5.8%)
Immune system disorders
Allergic reaction	31/322 (9.6%)		43/325 (13.2%)
Rhinitis	24/322 (7.5%)		25/325 (7.7%)
Infections and infestations
Febrile Neutropenia	17/322 (5.3%)		10/325 (3.1%)
Infections with normal ANC Ungual	17/322 (5.3%)		3/325 (0.9%)
Infections with normal ANC Upper Airway NOS	27/322 (8.4%)		21/325 (6.5%)
Musculoskeletal and connective tissue disorders
Pain - back	49/322 (15.2%)		63/325 (19.4%)
Pain - bone	61/322 (18.9%)		66/325 (20.3%)
Pain - chest/thorax NOS	7/322 (2.2%)		18/325 (5.5%)
Pain - extremity limb	30/322 (9.3%)		41/325 (12.6%)
Pain - joint	69/322 (21.4%)		76/325 (23.4%)
Pain - muscle	76/322 (23.6%)		73/325 (22.5%)
Pain - bone	25/322 (7.8%)		37/325 (11.4%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Pain - tumour pain	16/322 (5%)		20/325 (6.2%)
Nervous system disorders
Dizziness	27/322 (8.4%)		37/325 (11.4%)
Neuropathy-motor	15/322 (4.7%)		16/325 (4.9%)
Neuropathy-sensory	164/322 (50.9%)		159/325 (48.9%)
Pain - headache	52/322 (16.1%)		53/325 (16.3%)
Psychiatric disorders
Mood Alteration - Anxiety	30/322 (9.3%)		29/325 (8.9%)
Mood Alteration - Depression	24/322 (7.5%)		25/325 (7.7%)
Reproductive system and breast disorders
Pain - breast	21/322 (6.5%)		24/325 (7.4%)
Respiratory, thoracic and mediastinal disorders
Cough	55/322 (17.1%)		74/325 (22.8%)
Dyspnea	68/322 (21.1%)		80/325 (24.6%)
Nasal - paranasal reactions	24/322 (7.5%)		18/325 (5.5%)
Skin and subcutaneous tissue disorders
Alopecia	217/322 (67.4%)		239/325 (73.5%)
Dry Skin	54/322 (16.8%)		36/325 (11.1%)
Flushing	17/322 (5.3%)		13/325 (4%)
Hand Foot Syndrome	24/322 (7.5%)		9/325 (2.8%)
Nail Changes	118/322 (36.6%)		73/325 (22.5%)
Puritis	44/322 (13.7%)		28/325 (8.6%)
Rash	186/322 (57.8%)		113/325 (34.8%)
Dermatology - Other	21/322 (6.5%)		13/325 (4%)
Rash	84/322 (26.1%)		39/325 (12%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety.