Chemotherapy and Lapatinib or Trastuzumab in Treating Women With HER2/Neu-Positive Metastatic Breast Cancer
March 4, 2025 updated by: Novartis Pharmaceuticals
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
This was a multi-center, multinational, randomized, open-label, Phase III study comparing combination taxane-based chemotherapy plus lapatinib to combination taxane-based chemotherapy plus trastuzumab in women with documented evidence of human epidermal growth factor receptor 2 (HER2) positive metastatic breast cancer (MBC) (by local or central laboratory testing) who had received no prior chemotherapy or HER2 targeted therapy in the metastatic setting.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Detailed Description
Subjects were stratified by
- Prior (neo) adjuvant HER2/neu targeted therapy (yes, no)
- Prior (neo) adjuvant taxane chemotherapy (yes, no)
- Planned taxane treatment (once weekly paclitaxel versus docetaxel once every 3 weeks)
- Liver metastasis (yes, no)
Subjects were randomized 1:1 to the following treatments to a planned sample size of approximately 600 subjects (to achieve 536 centrally confirmed HER2 positive subjects):
- Taxane based chemotherapy plus lapatinib for 24 weeks followed by single agent lapatinib
- Taxane based chemotherapy plus trastuzumab for 24 weeks followed by single agent trastuzumab
The choice of taxane (once weekly paclitaxel versus docetaxel once every 3 weeks) was at the discretion of the treating physician and was specified at the time of subject randomization.
A protocol-specified interim analysis was conducted on 27-Apr-2012, following which the participants in the Lapatinib plus taxane based chemotherapy arm could cross over to Taxane based chemotherapy plus Trastuzumab.
Study Type
Interventional
Enrollment (Actual)
652
Phase
- Phase 3
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Santa Fe, Argentina, 3000
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Tucuman, Argentina, 4000
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Buenos Aires
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Capital Federal, Buenos Aires, Argentina, C1426ANZ
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Capital Federal, Buenos Aires, Argentina, C1405CUB
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Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina, C1280AEB
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La Plata, Buenos Aires, Argentina, B1920CMK
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Río Negro
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Cipolletti, Río Negro, Argentina, R8324EMB
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Viedma, Río Negro, Argentina, R8500ACE
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Santa Fe
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Rosario, Santa Fe, Argentina, S2000KZE
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Australian Capital Territory
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Garran, Australian Capital Territory, Australia, 2606
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New South Wales
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Liverpool, New South Wales, Australia, 2170
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North Sydney, New South Wales, Australia, 2060
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Tweed Heads, New South Wales, Australia, 2485
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Queensland
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Woolloongabba, Queensland, Australia, 4102
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South Australia
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Adelaide, South Australia, Australia, 5000
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Bedford Park, South Australia, Australia, 5042
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Kurralta Park, South Australia, Australia, 5037
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Tasmania
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Hobart, Tasmania, Australia, 7000
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Victoria
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Box Hill, Victoria, Australia, 3128
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Fitzroy, Victoria, Australia, 3065
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Wodonga, Victoria, Australia, 3690
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Western Australia
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Subiaco, Western Australia, Australia, 6008
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Gent, Belgium, 9000
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Jette, Belgium, 1090
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Liege, Belgium, 4000
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Namur, Belgium, 5000
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Quebec, Canada, G1S 4L8
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Alberta
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Edmonton, Alberta, Canada, T6G 1Z2
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British Columbia
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Kelowna, British Columbia, Canada, V1Y 5L3
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Surrey, British Columbia, Canada, V3V 1Z2
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Vancouver, British Columbia, Canada, V5Z 4E6
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Victoria, British Columbia, Canada, V8R 6V5
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Manitoba
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Winnipeg, Manitoba, Canada, R3E 0V9
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New Brunswick
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Moncton, New Brunswick, Canada, E1C 6Z8
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Saint John, New Brunswick, Canada, E2L 4L2
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Ontario
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Barrie, Ontario, Canada, L4M 6M2
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Hamilton, Ontario, Canada, L8V 5C2
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Kingston, Ontario, Canada, K7L 5P9
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London, Ontario, Canada, N6A 4L6
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Newmarket, Ontario, Canada, L3Y 2P9
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Ottawa, Ontario, Canada, K1H 8L6
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Sault Ste. Marie, Ontario, Canada, P6B 0A8
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St Catharines, Ontario, Canada, L2R 7C6
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Sudbury, Ontario, Canada, P3E 5J1
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Thunder Bay, Ontario, Canada, P7B 6V4
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Prince Edward Island
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Charlottetown, Prince Edward Island, Canada, C1A 8T5
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Quebec
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Montreal, Quebec, Canada, H2W 1S6
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Montreal, Quebec, Canada, H1T 2M4
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Montreal, Quebec, Canada, H2L 4M1
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Saskatchewan
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Regina, Saskatchewan, Canada, S4T 7T1
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Saskatoon, Saskatchewan, Canada, S7N 4H4
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Angers, France, 49033
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Bordeaux, France, 33075
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Bordeaux, France, 33077
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Caen Cedex 05, France, 14076
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Marseille cedex 9, France, 13273
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Metz-Tessy, France, 74370
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Nantes cedex, France, 44202
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Paris, France, 75014
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Strasbourg, France, 67085
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Berlin, Germany, 10117
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Berlin, Germany, 10367
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Brandenburg, Germany, 14770
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Hamburg, Germany, 22081
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Hamburg, Germany, 20095
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Hamburg, Germany, 22767
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Baden-Wuerttemberg
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Heidelberg, Baden-Wuerttemberg, Germany, 69115
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Stuttgart, Baden-Wuerttemberg, Germany, 70190
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Bayern
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Coburg, Bayern, Germany, 96450
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Eggenfelden, Bayern, Germany, 84307
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Fuerth, Bayern, Germany, 90766
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Regensburg, Bayern, Germany, 93049
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Rosenheim, Bayern, Germany, 83022
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Weiden, Bayern, Germany, 92637
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Brandenburg
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Fuerstenwalde, Brandenburg, Germany, 15517
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Hessen
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Frankfurt, Hessen, Germany, 60596
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Fulda, Hessen, Germany, 36043
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Lich, Hessen, Germany, 35423
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Niedersachsen
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Goslar, Niedersachsen, Germany, 38642
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Hannover, Niedersachsen, Germany, 30559
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Leer, Niedersachsen, Germany, 26789
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Nordrhein-Westfalen
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Bielefeld, Nordrhein-Westfalen, Germany, 33611
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Bonn, Nordrhein-Westfalen, Germany, 53113
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Coesfeld, Nordrhein-Westfalen, Germany, 48653
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Essen, Nordrhein-Westfalen, Germany, 45122
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Koeln, Nordrhein-Westfalen, Germany, 51067
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Porta Westfalica, Nordrhein-Westfalen, Germany, 32457
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Troisdorf, Nordrhein-Westfalen, Germany, 53840
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Velbert, Nordrhein-Westfalen, Germany, 42551
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Witten, Nordrhein-Westfalen, Germany, 58452
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Rheinland-Pfalz
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Koblenz, Rheinland-Pfalz, Germany, 56068
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Saarland
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Saarbruecken, Saarland, Germany, 66113
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Sachsen
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Dresden, Sachsen, Germany, 01127
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Sachsen-Anhalt
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Halle, Sachsen-Anhalt, Germany, 06120
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Schleswig-Holstein
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Luebeck, Schleswig-Holstein, Germany, 23538
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Bangalore, India, 560038
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Nagpur, India, 440010
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Pune, India, 411001
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Beer-Sheva, Israel, 84101
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Holon, Israel, 58100
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Petah-Tikva, Israel, 49100
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Poriya, Israel, 15208
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Ramat Gan, Israel, 52621
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Chieti, Italy, 66100
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Friuli-Venezia-Giulia
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Aviano (pn), Friuli-Venezia-Giulia, Italy, 33081
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Lazio
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Roma, Lazio, Italy, 00189
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Sora (FR), Lazio, Italy, 03039
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Liguria
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Genova, Liguria, Italy, 16132
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Puglia
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Lecce, Puglia, Italy, 73100
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Sardegna
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Sassari, Sardegna, Italy, 07100
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Toscana
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Prato (PO), Toscana, Italy, 59100
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Aichi, Japan, 464-8681
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Chiba, Japan, 277-8577
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Ehime, Japan, 791-0280
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Kagoshima, Japan, 892-0833
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Kanagawa, Japan, 241-8515
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Osaka, Japan, 540-0006
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Osaka, Japan, 565-0871
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Saitama, Japan, 350-1298
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Saitama, Japan, 362-0806
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Shizuoka, Japan, 411-8777
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Tokyo, Japan, 104-8560
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Tokyo, Japan, 113-8677
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Gyeonggi-do, Korea, Republic of, 10408
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Gyeonggi-do, Korea, Republic of, 410-769
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Seoul, Korea, Republic of, 03722
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Seoul, Korea, Republic of, 120-752
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Seoul, Korea, Republic of, 110-744
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Songpa-gu, Seoul, Korea, Republic of, 138-736
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Mexico City, Mexico, CP 14080
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Morelos
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Cuernavaca, Morelos, Mexico, 62450
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Sonora
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Ciudad Obregon, Sonora, Mexico, 85000
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Amsterdam, Netherlands, 1091 AC
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Delft, Netherlands, 2625 AD
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Dordrecht, Netherlands, 3318 AT
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Maastricht, Netherlands, 6229 HX
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Gdansk, Poland, 80-219
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Lodz, Poland, 93-509
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Olsztyn, Poland, 10-226
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Olsztyn, Poland, 10-513
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Plock, Poland, 09-400
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Rzeszow, Poland, 35-021
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Warszawa, Poland, 02-781
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Warszawa, Poland, 04-125
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Arkhangelsk, Russian Federation, 163045
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Ivanovo, Russian Federation, 153013
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Kazan, Russian Federation, 420029
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Kirov, Russian Federation, 610021
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Lipetsk, Russian Federation, 398005
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Moscow, Russian Federation, 115 478
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Ryazan, Russian Federation, 390011
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St. Petersburg, Russian Federation, 197758
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St. Petersburg, Russian Federation, 197022
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Stavropol, Russian Federation, 355047
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Ufa, Russian Federation, 450054
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Ufa,, Russian Federation, 450054
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Alcorcon, Spain, 28922
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Alicante, Spain, 03010
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Badalona, Spain, 08916
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Barcelona, Spain, 08036
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Elche, Spain, 03202
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Girona, Spain, 17007
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Jaen, Spain, 23007
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La Coruna, Spain, 15009
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Lugo, Spain, 27003
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Madrid, Spain, 28034
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Madrid, Spain, 28007
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Madrid, Spain, 28040
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Majadahonda (Madrid), Spain, 28222
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Pozuelo De Alarcon (Madrid), Spain, 28223
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Sevilla, Spain, 41013
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Valencia, Spain, 46009
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Changhua, Taiwan, 500
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Taichung, Taiwan, 404
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Tainan County, Taiwan, 736
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Taipei, Taiwan, 100
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Taipei, Taiwan, 112
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Bangkok, Thailand, 10700
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Chiangmai, Thailand, 50200
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Dnepropetrovsk, Ukraine, 49102
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Dnipropetrovsk, Ukraine, 49100
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Lviv, Ukraine, 79031
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Sumy, Ukraine, 40005
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Bournemouth, United Kingdom, BH7 7DW
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Brighton, United Kingdom, BN2 5BE
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Chelmsford, United Kingdom, CM1 7ET
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Cheltenham, United Kingdom, GL53 7AN
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Colchester, United Kingdom, CO3 3NB
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Cottingham, Hull, United Kingdom, HU16 5JQ
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Derby, United Kingdom, DE22 3NE
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Edmonton, United Kingdom, N18 1QX
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Guildford, United Kingdom, GU2 7XX
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Harrogate, United Kingdom, HG2 7SX
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Huddersfield, United Kingdom, HD3 3EA
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London, United Kingdom, SW3 6JJ
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Newcastle upon Tyne, United Kingdom, NE7 7DN
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Norwich, United Kingdom, NR4 7UY
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Nottingham, United Kingdom, NG5 1PB
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Oxford, United Kingdom, OX3 7LJ
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Poole, Dorset, United Kingdom, BH15 2JB
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Sheffield, United Kingdom, S10 2SJ
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Shrewsbury, United Kingdom, SY3 8XQ
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Sutton, United Kingdom, SM2 5PT
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Whitchurch, Cardiff, United Kingdom, CF14 2TL
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York, United Kingdom, YO31 8HE
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Alaska
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Anchorage, Alaska, United States, 99508
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Arizona
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Tucson, Arizona, United States, 85715
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Arkansas
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Hot Springs, Arkansas, United States, 71913
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California
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Berkeley, California, United States, 94704
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Highland, California, United States, 92346
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Montebello, California, United States, 90640
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Colorado
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Colorado Springs, Colorado, United States, 80907
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Denver, Colorado, United States, 80204
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Connecticut
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Greenwich, Connecticut, United States, 06830
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Southington, Connecticut, United States, 06489
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Stamford, Connecticut, United States, 06902-3628
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Trumbull, Connecticut, United States, 06611
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Waterbury, Connecticut, United States, 06708
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Florida
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Kissimmee, Florida, United States, 34741
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Loxahatchee Groves, Florida, United States, 33470
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New Port Richey, Florida, United States, 34655
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Georgia
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Augusta, Georgia, United States, 30901
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Lawrenceville, Georgia, United States, 30046
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Savannah, Georgia, United States, 31405
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Idaho
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Post Falls, Idaho, United States, 83854
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Illinois
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Chicago, Illinois, United States, 60657
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Oak Lawn, Illinois, United States, 60453
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Indiana
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Evansville, Indiana, United States, 47713
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Goshen, Indiana, United States, 46526
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Indianapolis, Indiana, United States, 46237
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Munster, Indiana, United States, 46321
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New Albany, Indiana, United States, 47150
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Maryland
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Towson, Maryland, United States, 21204
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Wheaton, Maryland, United States, 20902
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Montana
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Bozeman, Montana, United States, 59715
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Nebraska
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Grand Island, Nebraska, United States, 68803
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Kearney, Nebraska, United States, 68845
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Kearney, Nebraska, United States, 68847
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New Jersey
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Denville, New Jersey, United States, 07834
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Parsippany, New Jersey, United States, 07054
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New York
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Cooperstown, New York, United States, 13326
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North Carolina
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Greensboro, North Carolina, United States, 27403
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Ohio
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Canton, Ohio, United States, 44718
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Wooster, Ohio, United States, 44691
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Oregon
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Portland, Oregon, United States, 97227
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Pennsylvania
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Pittsburgh, Pennsylvania, United States, 15212-4772
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South Carolina
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Columbia, South Carolina, United States, 29210
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Tennessee
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Memphis, Tennessee, United States, 38120
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Virginia
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Chesapeake, Virginia, United States, 23320
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Salem, Virginia, United States, 24153
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Washington
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Bellevue, Washington, United States, 98004
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Kirkland, Washington, United States, 98034
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Mount Vernon, Washington, United States, 98273
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Seattle, Washington, United States, 98109
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Sequim, Washington, United States, 98382
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Tacoma, Washington, United States, 98405
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Wenatchee, Washington, United States, 98801
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Wisconsin
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Milwaukee, Wisconsin, United States, 53226
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Description
Key inclusion criteria:
- Histologically confirmed adenocarcinoma of the breast.
- MBC (stage IV) at primary diagnosis or at relapse after curative intent therapy.
Local or central laboratory confirmed HER2/neu overexpressing and/or amplified disease in the invasive component of the primary or metastatic lesion as defined by:
- 3+ over expression by immunohistochemistry (IHC) (>30% of invasive tumour cells);
- 2+ or 3+ (in 30% or less neoplastic cells) overexpression by IHC analysis AND fluorescence or chromogenic in situ hybridization (FISH/CISH) test demonstrating HER2/neu gene amplification;
- 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]
Subjects must have had evidence of metastatic disease, but measurable disease was not mandatory. To be considered evaluable for overall response rate (CR and PR), subjects must have had at least 1 measurable lesion as follows:
- X-ray, physical exam >=20 mm.
- Conventional computed tomography (CT) scan, magnetic resonance imaging (MRI) >=20 mm.
- Spiral CT scan >=10 mm.
Key exclusion criteria:
- Subjects with a history of other malignancies, except: adequately treated ductal carcinoma in-situ or lobular carcinoma in-situ, adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumor (non-breast) curatively treated with no evidence of disease for >=5 years.
- Subjects who had received prior chemotherapy, immunotherapy, biologic therapy or HER2/neu targeted therapy for recurrent or MBC.
- Subjects receiving ongoing anti-cancer treatment or other investigational anti-cancer agents for breast cancer or subjects who had used an investigational drug within 30 days or 5 half-lives (if known), whichever was longer, preceding the date of randomization.
- Subjects with: CNS metastases (including leptomeningeal involvement), serious cardiac illness, peripheral neuropathy grade 2 or greater, subjects with gastrointestinal tract disease, subjects receiving CYP3A4 inhibitors or inducers, and subjects with history of allergic or hypersensitivity reactions to any study drug or their excipients.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
Active Comparator: Lapatinib
Plus taxane based chemotherapy
|
75mg/m2 IV q 3 weekly, day 1 of a 3 week cycle for 8 cycles plus G-CSF (when given together with lapatinib).
80mg/m2 IV q weekly days 1, 8 and 15 of a 4-week cycle for 6 cycles.
1250 mg once daily (while given with taxane).
1500mg once daily (when given alone after taxane completion).
|
|
Active Comparator: Trastuzumab
Plus taxane based chemotherapy.
|
75mg/m2 IV q 3 weekly, day 1 of a 3 week cycle for 8 cycles plus G-CSF (when given together with lapatinib).
80mg/m2 IV q weekly days 1, 8 and 15 of a 4-week cycle for 6 cycles.
IV q weekly (loading dose 4mg/kg; subsequent doses 2mg/kg) or IV q 3 weekly (loading dose 8mg/kg, subsequent doses 6mg/kg).
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Progression Free Survival (PFS) at the Time of Primary Results
Time Frame: From date of randomization until date of progression or date of death from any cause, whichever comes first, assessed up to approximately 39 months
|
Progression-free survival (PFS) is the time from randomization to the earliest date of RECIST 1.0 assessment of disease progression (with radiological evidence), death from any cause, or censoring.
Disease progression was assessed by the Investigator and defined by RECIST v1.0 as a 20% increase in the sum of the longest diameter of target lesions, a measurable increase in a non-target lesion, or the appearance of new lesions.
|
From date of randomization until date of progression or date of death from any cause, whichever comes first, assessed up to approximately 39 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Progression Free Survival (PFS) at the Time of Final Analysis
Time Frame: From date of randomization until date of progression or date of death from any cause, whichever comes first, assessed up to approximately 45 months
|
Progression-free survival (PFS) is the time from randomization to the earliest date of RECIST 1.0 assessment of disease progression (with radiological evidence), death from any cause, or censoring.
Disease progression was assessed by the Investigator and defined by RECIST v1.0 as a 20% increase in the sum of the longest diameter of target lesions, a measurable increase in a non-target lesion, or the appearance of new lesions.
Subjects who crossover the treatment to Trastuzumab (TTax/T) after interim analysis, were censored at the last PFS assessment before crossover.
|
From date of randomization until date of progression or date of death from any cause, whichever comes first, assessed up to approximately 45 months
|
|
Overall Survival (OS) (IIT Population)
Time Frame: From date of randomization until date of death from any cause, assessed up approximately 165 months
|
Overall Survival (OS) was defined as the time interval between the date of randomization and the date of death from any cause.
Subjects who were still alive at the time of the final analysis or became lost to follow-up, were censored at their last contact date.
Subjects who crossover the treatment to Trastuzumab (TTax/T) after interim analysis, were censored at last known alive date prior to crossover.
|
From date of randomization until date of death from any cause, assessed up approximately 165 months
|
|
Overall Survival (OS) (Central HER2+ Population)
Time Frame: From date of randomization until date of death from any cause, assessed up approximately 165 months
|
Overall Survival (OS) was defined as the time interval between the date of randomization and the date of death from any cause.
Subjects who were still alive at the time of the final analysis or became lost to follow-up, were censored at their last contact date.
Subjects who crossover the treatment to Trastuzumab (TTax/T) after interim analysis, were censored at last known alive date prior to crossover.
|
From date of randomization until date of death from any cause, assessed up approximately 165 months
|
|
Incidence of Central Nervous System (CNS) Metastasis at First Progression (IIT Population)
Time Frame: From date of randomization to CNS metastases at time of first progression, assessed up approximately 45 months
|
The incidence of Central Nervous System (CNS) metastasis at first progression was defined as the ratio of the number of subjects with CNS metastasis at progression over the total number of subjects.
|
From date of randomization to CNS metastases at time of first progression, assessed up approximately 45 months
|
|
Incidence of Central Nervous System (CNS) Metastasis at First Progression (Central HER2+ Population)
Time Frame: From date of randomization to CNS metastases at time of first progression, assessed up approximately 45 months
|
The incidence of Central Nervous System (CNS) metastasis at first progression was defined as the ratio of the number of subjects with CNS metastasis at progression over the total number of subjects.
|
From date of randomization to CNS metastases at time of first progression, assessed up approximately 45 months
|
|
Time to Central Nervous System (CNS) Metastasis (IIT Population)
Time Frame: From date of randomization to CNS metastases at time of first progression, assessed up approximately 45 months
|
Time to Central Nervous System (CNS) metastasis was defined as the time from randomization until disease progression where CNS metastasis was documented at the time of first breast cancer progression.
Subjects who crossed over the treatment to Trastuzumab (TTax/T) after interim analysis, were censored at RECIST assessment prior to crossover.
|
From date of randomization to CNS metastases at time of first progression, assessed up approximately 45 months
|
|
Time to Central Nervous System (CNS) Metastasis (Central HER2+ Population)
Time Frame: From date of randomization to CNS metastases at time of first progression, assessed up approximately 45 months
|
Time to Central Nervous System (CNS) metastasis was defined as the time from randomization until disease progression where CNS metastasis was documented at the time of first breast cancer progression.
Subjects who crossed over the treatment to Trastuzumab (TTax/T) after interim analysis, were censored at RECIST assessment prior to crossover.
|
From date of randomization to CNS metastases at time of first progression, assessed up approximately 45 months
|
|
Overall Response Rate (ORR) (IIT Population)
Time Frame: From date of randomization until date of progression or date of death from any cause, whichever comes first, assessed up approximately 45 months
|
Overall Response Rate (ORR) was defined as the proportion of participants with Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR). The ORR was calculated from the Investigator's assessment of response based on RECIST 1.1. Subjects with an unknown or missing response were treated as non-responders; i.e., they were included in the denominator when calculating the percentages. Per Response Evaluation Criteria In Solid Tumors (RECIST v1.1) for target lesions and assessed by MRI:
|
From date of randomization until date of progression or date of death from any cause, whichever comes first, assessed up approximately 45 months
|
|
Overall Response Rate (ORR) (Central HER2+ Population)
Time Frame: From date of randomization until date of progression or date of death from any cause, whichever comes first, assessed up approximately 45 months
|
Overall Response Rate (ORR) was defined as the proportion of participants with Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR). The ORR was calculated from the Investigator's assessment of response based on RECIST 1.1. Subjects with an unknown or missing response were treated as non-responders; i.e., they were included in the denominator when calculating the percentages. Per Response Evaluation Criteria In Solid Tumors (RECIST v1.1) for target lesions and assessed by MRI:
|
From date of randomization until date of progression or date of death from any cause, whichever comes first, assessed up approximately 45 months
|
|
Clinical Benefit Response (CBR) (IIT Population)
Time Frame: From date of randomization until date of progression or date of death from any cause, whichever comes first, assessed up approximately 45 months
|
Clinical Benefit Response (CBR) was defined as the percentage with evidence of Complete Response (CR), Partial Response (PR) (participants with at least 1 measurable lesion at baseline), or maintaining Stable Disease (SD) for at least 24 weeks (all subjects, with or without measurable disease at baseline) while on study, according to the investigator assessment of response per RECIST 1.1 criteria.
Participants were considered to be positive (Yes) for CBR if they experienced any CR or PR for any duration prior to progressive disease.
Participants were considered to be negative (No) for CBR if they had progressive disease prior to Week 24 without prior confirmed CR or PR.
|
From date of randomization until date of progression or date of death from any cause, whichever comes first, assessed up approximately 45 months
|
|
Clinical Benefit Response (CBR) (Central HER2+ Population)
Time Frame: From date of randomization until date of progression or date of death from any cause, whichever comes first, assessed up approximately 45 months
|
Clinical Benefit Response (CBR) was defined as the percentage with evidence of Complete Response (CR), Partial Response (PR) (participants with at least 1 measurable lesion at baseline), or maintaining Stable Disease (SD) for at least 24 weeks (all subjects, with or without measurable disease at baseline) while on study, according to the investigator assessment of response per RECIST 1.1 criteria.
Participants were considered to be positive (Yes) for CBR if they experienced any CR or PR for any duration prior to progressive disease.
Participants were considered to be negative (No) for CBR if they had progressive disease prior to Week 24 without prior confirmed CR or PR.
|
From date of randomization until date of progression or date of death from any cause, whichever comes first, assessed up approximately 45 months
|
|
Time to Response (TTR) (IIT Population)
Time Frame: From date of randomization until date of first response, assessed up approximately 45 months
|
Time to Response was defined as the time from randomization to the earliest date of Complete Response (CR) or Partial Response (PR).
The event of first response was the first CR or PR; censoring was at PD date for those who progressed or at the last RECIST date if no progression occurred.
|
From date of randomization until date of first response, assessed up approximately 45 months
|
|
Time to Response (TTR) (Central HER2+ Population)
Time Frame: From date of randomization until date of progression or date of death from any cause, whichever comes first, assessed up approximately 45 months
|
Time to Response was defined as the time from randomization to the earliest date of Complete Response (CR) or Partial Response (PR).
The event of first response was the first CR or PR; censoring was at PD date for those who progressed or at the last RECIST date if no progression occurred.
|
From date of randomization until date of progression or date of death from any cause, whichever comes first, assessed up approximately 45 months
|
|
Duration of Response (DoR) (IIT Population)
Time Frame: From first documented evidence of CR or PR (the response prior to confirmation) until time of documented disease progression or death due to any cause, whichever comes first, assessed up approximately 165 months
|
Duration of Response (DOR) was defined as the duration between the date of first documented Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR) and the date of first documented sign of Progressive Disease or Death, with censoring at the last RECIST date if no progression occurred.
|
From first documented evidence of CR or PR (the response prior to confirmation) until time of documented disease progression or death due to any cause, whichever comes first, assessed up approximately 165 months
|
|
Duration of Response (DoR) (Central HER2+ Population)
Time Frame: From first documented evidence of CR or PR (the response prior to confirmation) until time of documented disease progression or death due to any cause, whichever comes first, assessed up approximately 165 months
|
Duration of Response (DOR) was defined as the duration between the date of first documented Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR) and the date of first documented sign of Progressive Disease or Death, with censoring at the last RECIST date if no progression occurred.
|
From first documented evidence of CR or PR (the response prior to confirmation) until time of documented disease progression or death due to any cause, whichever comes first, assessed up approximately 165 months
|
|
EORTC QLQ-C30 Global Score at 12 Weeks
Time Frame: Week 12
|
The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQC-30) 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.
|
Week 12
|
|
Number of Participants Achieving European Quality of Life (EuroQol) - 5 Domain (EQ-5D) Score (Canadian and Australian Centers Only)
Time Frame: Week 12, Week 24, Week 36, Week 48, Week 60, Week 72, Week 84, Week 96, Week 120, Week 144
|
The European Quality of Life (EuroQol) - 5 Domain (EQ-5D) self-administered questionnaire consists of two pages comprising the EQ-5D descriptive system and the EQ Visual Analogue Scale (VAS).
The EQ-5D descriptive system comprises five dimensions of health (mobility, self-care, usual activities, pain/discomfort, anxiety/depression) and each dimension comprises three levels (no problems, some problems, extreme problems, unable to perform the activity).
|
Week 12, Week 24, Week 36, Week 48, Week 60, Week 72, Week 84, Week 96, Week 120, Week 144
|
|
Change From Baseline in the EQ-VAS Score (Canadian and Australian Centers Only)
Time Frame: Baseline, Week 12, Week 24, Week 36, Week 48, Week 60, Week 72, Week 84, Week 96, Week 120, Week 144
|
The European Quality of Life (EuroQol) - 5 Domain (EQ-5D) self-administered questionnaire consists of two pages comprising the EQ-5D descriptive system and the EQ Visual Analogue Scale (VAS).
The EQ VAS records the patient's self-rated health on a vertical visual analogue 0-100 scale, where the endpoints are labelled 'The best health you can imagine' (100) and 'The worst health you can imagine' (0).
|
Baseline, Week 12, Week 24, Week 36, Week 48, Week 60, Week 72, Week 84, Week 96, Week 120, Week 144
|
|
Number of Participants With Healthcare Utilization (Canadian and Australian Centers Only)
Time Frame: From date of randomization till 28 days safety follow-up, assessed up to 40 months
|
The measures of healthcare resource utilization collected were categorized: hospitalization/inpatient visit, Institutionalized, Outpatient visit.
|
From date of randomization till 28 days safety follow-up, assessed up to 40 months
|
|
Number of Participant Hospitalized (Canadian and Australian Centers Only)
Time Frame: From date of randomization till 28 days safety follow-up, assessed up to 40 months
|
The number of hospitalizations were categorized: >0 and =<2, >2 and =<4 and >4.
|
From date of randomization till 28 days safety follow-up, assessed up to 40 months
|
|
Total and Average Duration of Hospitalization (Canadian and Australian Centers Only)
Time Frame: From date of randomization till 28 days safety follow-up, assessed up to 40 months
|
The total duration of hospitalization in days and average duration of each hospitalization in days were summarized using descriptive statistics.
|
From date of randomization till 28 days safety follow-up, assessed up to 40 months
|
|
Reasons for Hospitalization (Canadian and Australian Centers Only)
Time Frame: From date of randomization till 28 days safety follow-up, assessed up to 40 months
|
The reasons for hospitalization were categorized: Breast Cancer, Febrile Neutropenia, Infection, Other and Pneumonia.
|
From date of randomization till 28 days safety follow-up, assessed up to 40 months
|
|
Type of Ward (Hospital Unit) (Canadian and Australian Centers Only)
Time Frame: From date of randomization till 28 days safety follow-up, assessed up to 40 months
|
The type of ward (hospital unit) were categorized: general ward, intensive care unit, oncology ward, rehabilitation unit and other.
|
From date of randomization till 28 days safety follow-up, assessed up to 40 months
|
|
Discharge Destinations (Canadian and Australian Centers Only)
Time Frame: From date of randomization till 28 days safety follow-up, assessed up to 40 months
|
The discharge destinations were categorized: died, home, rehabilitation facility and transfer to other hospital.
|
From date of randomization till 28 days safety follow-up, assessed up to 40 months
|
|
Estrogen Receptor (ER) and Progesterone Receptor (PgR) Status
Time Frame: Up to approximately 39 months
|
Immunohistochemistry (IHC) analysis of estrogen receptor (ER) and progesterone receptor (PgR) were performed as part of the mandatory central laboratory testing for protocol-specified biomarkers.
|
Up to approximately 39 months
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Investigators
- Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
- Gelmon KA, Boyle FM, Kaufman B, Huntsman DG, Manikhas A, Di Leo A, Martin M, Schwartzberg LS, Lemieux J, Aparicio S, Shepherd LE, Dent S, Ellard SL, Tonkin K, Pritchard KI, Whelan TJ, Nomikos D, Nusch A, Coleman RE, Mukai H, Tjulandin S, Khasanov R, Rizel S, Connor AP, Santillana SL, Chapman JA, Parulekar WR. Lapatinib or Trastuzumab Plus Taxane Therapy for Human Epidermal Growth Factor Receptor 2-Positive Advanced Breast Cancer: Final Results of NCIC CTG MA.31. J Clin Oncol. 2015 May 10;33(14):1574-83. doi: 10.1200/JCO.2014.56.9590. Epub 2015 Mar 16.
- Ho D, Huang J, Chapman JW, Leitzel K, Ali SM, Shepherd L, Parulekar WR, Ellis CE, Crescnzo RJ, Zhu L, Virk S, Nomikos D, Aparicio S, Gelmon KA, Carney WP, Lipton A. Impact of serum HER2, TIMP-1, and CAIX on outcome for HER2+ metastatic breast cancer patients: CCTG MA.31 (lapatinib vs. trastuzumab). Breast Cancer Res Treat. 2017 Aug;164(3):571-580. doi: 10.1007/s10549-017-4273-x. Epub 2017 May 8.
- Liu S, Chen B, Burugu S, Leung S, Gao D, Virk S, Kos Z, Parulekar WR, Shepherd L, Gelmon KA, Nielsen TO. Role of Cytotoxic Tumor-Infiltrating Lymphocytes in Predicting Outcomes in Metastatic HER2-Positive Breast Cancer: A Secondary Analysis of a Randomized Clinical Trial. JAMA Oncol. 2017 Nov 9;3(11):e172085. doi: 10.1001/jamaoncol.2017.2085. Epub 2017 Nov 9.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
October 7, 2008
Primary Completion (Actual)
August 1, 2012
Study Completion (Actual)
July 27, 2022
Study Registration Dates
First Submitted
April 25, 2008
First Submitted That Met QC Criteria
April 25, 2008
First Posted (Estimated)
April 28, 2008
Study Record Updates
Last Update Posted (Actual)
March 25, 2025
Last Update Submitted That Met QC Criteria
March 4, 2025
Last Verified
March 1, 2025
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Neoplasms by Site
- Neoplasms
- Skin Diseases
- Breast Diseases
- Breast Neoplasms
- Antineoplastic Agents, Immunological
- Tyrosine Kinase Inhibitors
- Antineoplastic Agents
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Protein Kinase Inhibitors
- Tubulin Modulators
- Antimitotic Agents
- Mitosis Modulators
- Antineoplastic Agents, Phytogenic
- Docetaxel
- Trastuzumab
- Lapatinib
- Paclitaxel
Other Study ID Numbers
- 108919
- CLAP016A2303 (Other Identifier: Novartis)
- CAN-NCIC-MA31 (Other Grant/Funding Number: NCI US - Physician Data Query)
- 2007-004568-27 (EudraCT Number)
- CDR0000594764 (Other Identifier: PDQ)
- EGF108919 (Other Identifier: GSK)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
YES
IPD Plan Description
Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.
This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.