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NCT00667251

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

Completed Phase 3 Results posted Last updated 21 March 2025
What this trial tests

Phase 3 trial testing trastuzumab in Breast Cancer in 652 participants. Completed in 27 July 2022.

Timeline
7 October 2008
Primary endpoint
1 August 2012
27 July 2022

Quick facts

Lead sponsorNovartis Pharmaceuticals
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingnone
Primary purposetreatment
Enrollment652
Start date7 October 2008
Primary completion1 August 2012
Estimated completion27 July 2022
Sites257 locations across Italy, Japan, Taiwan, Poland, South Korea, Netherlands, Russia, Belgium

Drugs / interventions tested

Conditions studied

Sponsor

Novartis Pharmaceuticals — full company profile →

Who can join

18 and older, female only, with Breast Cancer. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Progression Free Survival (PFS) at the Time of Primary Results Primary · 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.

Intent-to-Treat (ITT) population
GroupValue95% CI
Lapatinib (LTax/L)8.970.30 – 32.69
Trastuzumab (TTax/T)11.300.30 – 38.54
centrally-confirmed HER2 positive population
GroupValue95% CI
Lapatinib (LTax/L)9.130.30 – 32.69
Trastuzumab (TTax/T)13.630.30 – 38.54
Progression Free Survival (PFS) at the Time of Final Analysis Secondary · 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.

Intent-to-Treat (ITT) population
GroupValue95% CI
Lapatinib (LTax/L)9.18.5 – 10.8
Trastuzumab (TTax/T)11.510.9 – 13.8
centrally-confirmed HER2 positive population
GroupValue95% CI
Lapatinib (LTax/L)9.48.5 – 11.0
Trastuzumab (TTax/T)13.811.2 – 14.2
Overall Survival (OS) (IIT Population) Secondary · 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.

GroupValue95% CI
Lapatinib (LTax/L)30.024.2 – NA
Trastuzumab (TTax/T)38.331.0 – NA
Overall Survival (OS) (Central HER2+ Population) Secondary · 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.

GroupValue95% CI
Lapatinib (LTax/L)30.024.2 – NA
Trastuzumab (TTax/T)NANA – NA
Incidence of Central Nervous System (CNS) Metastasis at First Progression (IIT Population) Secondary · 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.

Subject had CNS metastasis at first progression = Yes
GroupValue95% CI
Lapatinib (LTax/L)47
Trastuzumab (TTax/T)55
Crossed Over to Trastuzumab (TTax/T) After IA Results1
Overall TTax/T56
Subject had CNS metastasis at first progression = No
GroupValue95% CI
Lapatinib (LTax/L)155
Trastuzumab (TTax/T)119
Crossed Over to Trastuzumab (TTax/T) After IA Results4
Overall TTax/T123
Subject had CNS metastasis at first progression = Unknown
GroupValue95% CI
Lapatinib (LTax/L)66
Trastuzumab (TTax/T)62
Crossed Over to Trastuzumab (TTax/T) After IA Results0
Overall TTax/T62
Incidence of Central Nervous System (CNS) Metastasis at First Progression (Central HER2+ Population) Secondary · 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.

Subject had CNS metastasis at first progression = Yes
GroupValue95% CI
Lapatinib (LTax/L)43
Trastuzumab (TTax/T)50
Crossed Over to Trastuzumab (TTax/T) After IA Results1
Overall TTax/T51
Subject had CNS metastasis at first progression = No
GroupValue95% CI
Lapatinib (LTax/L)128
Trastuzumab (TTax/T)92
Crossed Over to Trastuzumab (TTax/T) After IA Results3
Overall TTax/T95
Subject had CNS metastasis at first progression = Unknown
GroupValue95% CI
Lapatinib (LTax/L)53
Trastuzumab (TTax/T)44
Crossed Over to Trastuzumab (TTax/T) After IA Results0
Overall TTax/T44
Time to Central Nervous System (CNS) Metastasis (IIT Population) Secondary · 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.

GroupValue95% CI
Lapatinib (LTax/L)NANA – NA
Trastuzumab (TTax/T)NANA – NA
Time to Central Nervous System (CNS) Metastasis (Central HER2+ Population) Secondary · 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.

GroupValue95% CI
Lapatinib (LTax/L)NA25.4 – NA
Trastuzumab (TTax/T)NA27.7 – NA
Overall Response Rate (ORR) (IIT Population) Secondary · 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: * Complete Response (CR): Disappearance of all target and non-target lesions. * Partial Re

GroupValue95% CI
Lapatinib (LTax/L)64.258.0 – 70.1
Trastuzumab (TTax/T)63.357.3 – 69.1
Overall Response Rate (ORR) (Central HER2+ Population) Secondary · 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: * Complete Response (CR): Disappearance of all target and non-target lesions. * Partial Re

GroupValue95% CI
Lapatinib (LTax/L)66.760.0 – 72.9
Trastuzumab (TTax/T)67.460.8 – 73.5
Clinical Benefit Response (CBR) (IIT Population) Secondary · 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 t

GroupValue95% CI
Lapatinib (LTax/L)60.454.9 – 65.8
Trastuzumab (TTax/T)62.056.5 – 67.3
Clinical Benefit Response (CBR) (Central HER2+ Population) Secondary · 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 t

GroupValue95% CI
Lapatinib (LTax/L)61.155.0 – 67.0
Trastuzumab (TTax/T)65.259.1 – 70.9

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse Events (AEs) were collected from first dose of study medication until the last dose plus 28 days post-treat follow-up, assessed up to approximately 165 months. Deaths were recorded from study start date until end of survival follow-up phase (end of study), assessed up to approximately 166 months.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Lapatinib (LTax/L) - All Participants
Serious: 106/322 (33%)
Deaths: 21/326
Trastuzumab (TTax/T)
Serious: 66/325 (20%)
Deaths: 13/326
Lapatinib (LTax/L) - Crossed Over to Trastuzumab (TTax/T) After IA Results
Serious: 2/5 (40%)
Deaths: 0/5
Lapatinib (LTax/L) - All Participants (Post-treatment)
Serious: 0
Deaths: 82/301
Trastuzumab (TTax/T) (Post-treatment)
Serious: 0
Deaths: 73/312
Lapatinib (LTax/L) - Crossed Over to Trastuzumab (TTax/T) After IA Results (Post-treatment)
Serious: 0
Deaths: 0/5

Serious adverse events (115 terms)

ReactionSystemLapatinib (LTax/L) - All P…Trastuzumab (TTax/T)Lapatinib (LTax/L) - Cross…Lapatinib (LTax/L) - All P…Trastuzumab (TTax/T) (Post…Lapatinib (LTax/L) - Cross…
DiarrhoeaGastrointestinal disorders
Febrile neutropeniaGeneral disorders
Alanine aminotransferaseInvestigations
VomitingGastrointestinal disorders
InfectionInfections and infestations
PyrexiaGeneral disorders
PneumoniaInfections and infestations
Aspartate aminotransferaseInvestigations
Blood bilirubinInvestigations
NauseaGastrointestinal disorders
Neutrophil countInvestigations
FatigueGeneral disorders
CystitisInfections and infestations
PneumonitisRespiratory, thoracic and mediastinal disorders
EmbolismVascular disorders
SepsisInfections and infestations
Urinary tract infectionInfections and infestations
DehydrationMetabolism and nutrition disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
PruritusSkin and subcutaneous tissue disorders
Skin infectionSkin and subcutaneous tissue disorders
LeukocytosisBlood and lymphatic system disorders
Atrial fibrillationCardiac disorders
Gastrointestinal disorderGastrointestinal disorders
StomatitisGastrointestinal disorders
Other adverse events (61 terms — click to expand)

ReactionSystemLapatinib (LTax/L) - All P…Trastuzumab (TTax/T)Lapatinib (LTax/L) - Cross…Lapatinib (LTax/L) - All P…Trastuzumab (TTax/T) (Post…Lapatinib (LTax/L) - Cross…
DiarrhoeaGastrointestinal disorders
AlopeciaSkin and subcutaneous tissue disorders
FatigueGeneral disorders
RashSkin and subcutaneous tissue disorders
Peripheral sensory neuropathyNervous system disorders
NauseaGastrointestinal disorders
StomatitisGastrointestinal disorders
Nail disorderSkin and subcutaneous tissue disorders
Oedema peripheralCardiac disorders
Decreased appetiteMetabolism and nutrition disorders
ArthralgiaMusculoskeletal and connective tissue disorders
CoughRespiratory, thoracic and mediastinal disorders
VomitingGastrointestinal disorders
ConstipationGastrointestinal disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
Bone painMusculoskeletal and connective tissue disorders
MyalgiaMusculoskeletal and connective tissue disorders
Back painMusculoskeletal and connective tissue disorders
HeadacheNervous system disorders
InsomniaPsychiatric disorders
DyspepsiaGastrointestinal disorders
EpistaxisVascular disorders
Dry skinSkin and subcutaneous tissue disorders
Taste disorderGastrointestinal disorders
PyrexiaGeneral disorders
Pain in extremityMusculoskeletal and connective tissue disorders
Abdominal painGastrointestinal disorders
DizzinessNervous system disorders
PruritusSkin and subcutaneous tissue disorders
HypersensitivityImmune system disorders
Upper respiratory tract infectionInfections and infestations
Lacrimation increasedEye disorders
HypertensionVascular disorders
AnxietyPsychiatric disorders
Hot flushVascular disorders
RhinitisInfections and infestations
Palmar-plantar erythrodysaesthesia syndromeNervous system disorders
Depressed moodPsychiatric disorders
InfluenzaRespiratory, thoracic and mediastinal disorders
Oropharyngeal painRespiratory, thoracic and mediastinal disorders

Most-reported serious reactions: Diarrhoea, Febrile neutropenia, Alanine aminotransferase, Vomiting, Infection, Pyrexia, Pneumonia, Aspartate aminotransferase.

Data from ClinicalTrials.gov NCT00667251 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Ferroptosis in cancer: From molecular mechanisms to therapeutic strategies.
    Zhou Q, Meng Y, Li D, Yao L, et al · · 2024 · cited 439× · PMID 38453898 · DOI 10.1038/s41392-024-01769-5
  2. The role of lipid metabolic reprogramming in tumor microenvironment.
    Yang K, Wang X, Song C, He Z, et al · · 2023 · cited 175× · PMID 37064872 · DOI 10.7150/thno.82920
  3. Breast Cancer Brain Metastasis-Overview of Disease State, Treatment Options and Future Perspectives.
    Watase C, Shiino S, Shimoi T, Noguchi E, et al · · 2021 · cited 68× · PMID 33802424 · DOI 10.3390/cancers13051078
  4. Lapatinib for advanced or metastatic breast cancer.
    Opdam FL, Guchelaar HJ, Beijnen JH, Schellens JH. · · 2012 · cited 63× · PMID 22477724 · DOI 10.1634/theoncologist.2011-0461
  5. Magnetic nanoparticles for ferroptosis cancer therapy with diagnostic imaging.
    Ko MJ, Min S, Hong H, Yoo W, et al · · 2024 · cited 58× · PMID 37822917 · DOI 10.1016/j.bioactmat.2023.09.015
  6. Mechanisms of Resistance to Trastuzumab and Novel Therapeutic Strategies in HER2-Positive Breast Cancer.
    Wong AL, Lee SC. · · 2012 · cited 46× · PMID 22649737 · DOI 10.1155/2012/415170
  7. Role of Cytotoxic Tumor-Infiltrating Lymphocytes in Predicting Outcomes in Metastatic HER2-Positive Breast Cancer: A Secondary Analysis of a Randomized Clinical Trial.
    Liu S, Chen B, Burugu S, Leung S, et al · · 2017 · cited 40× · PMID 28750133 · DOI 10.1001/jamaoncol.2017.2085
  8. The Evolving Role of Ferroptosis in Breast Cancer: Translational Implications Present and Future.
    Lin HY, Ho HW, Chang YH, Wei CJ, et al · · 2021 · cited 30× · PMID 34572802 · DOI 10.3390/cancers13184576

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Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT00667251.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing