Trial Outcomes & Findings for A Study of Pertuzumab and Trastuzumab Subcutaneous (SC) Treatment in Combination With a Taxane in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Metastatic Breast Cancer (NCT NCT02019277)
NCT ID: NCT02019277
Last Updated: 2018-09-13
Results Overview
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Percentage of participants with AEs and SAEs was reported. AEs included both SAEs and non-SAEs. The 95% confidence interval (CI) was computed using Clopper-Pearson method.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
50 participants
Primary outcome timeframe
Baseline up to 28 days after last study drug administration (up to 36 months)
Results posted on
2018-09-13
Participant Flow
Participant milestones
| Measure |
Trastuzumab, Pertuzumab, and Taxane
Participants received first-line therapy with pertuzumab administered via intravenous (IV) infusion on Day 1 of first treatment cycle (1 cycle = 21 days) at a loading dose of 840 milligrams (mg), followed by 420 mg on Day 1 of each subsequent cycle; trastuzumab administered via subcutaneous (SC) injection at a dose of 600 mg on Day 2 of first treatment cycle, and on Day 1 of each subsequent cycle if both pertuzumab and trastuzumab were well tolerated in Cycle 1; and taxane treatment (docetaxel, paclitaxel, or nabpaclitaxel), administered at the discretion of the investigator, per routine clinical practices and local prescribing instructions. Participants continued study treatment until disease progression (PD), unacceptable toxicity, or withdrawal of consent. Participants with unacceptable toxicity or PD were switched to standard treatment of the investigator's choice. All participants were followed-up until withdrawal of consent, loss to follow-up, death, or study closure.
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|---|---|
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Overall Study
STARTED
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50
|
|
Overall Study
COMPLETED
|
38
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|
Overall Study
NOT COMPLETED
|
12
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Reasons for withdrawal
| Measure |
Trastuzumab, Pertuzumab, and Taxane
Participants received first-line therapy with pertuzumab administered via intravenous (IV) infusion on Day 1 of first treatment cycle (1 cycle = 21 days) at a loading dose of 840 milligrams (mg), followed by 420 mg on Day 1 of each subsequent cycle; trastuzumab administered via subcutaneous (SC) injection at a dose of 600 mg on Day 2 of first treatment cycle, and on Day 1 of each subsequent cycle if both pertuzumab and trastuzumab were well tolerated in Cycle 1; and taxane treatment (docetaxel, paclitaxel, or nabpaclitaxel), administered at the discretion of the investigator, per routine clinical practices and local prescribing instructions. Participants continued study treatment until disease progression (PD), unacceptable toxicity, or withdrawal of consent. Participants with unacceptable toxicity or PD were switched to standard treatment of the investigator's choice. All participants were followed-up until withdrawal of consent, loss to follow-up, death, or study closure.
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|---|---|
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Overall Study
Withdrawal by Subject
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3
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|
Overall Study
Death
|
7
|
|
Overall Study
Did no Cooperate
|
1
|
|
Overall Study
Adverse Event
|
1
|
Baseline Characteristics
A Study of Pertuzumab and Trastuzumab Subcutaneous (SC) Treatment in Combination With a Taxane in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Metastatic Breast Cancer
Baseline characteristics by cohort
| Measure |
Trastuzumab, Pertuzumab, and Taxane
n=50 Participants
Participants received first-line therapy with pertuzumab administered via IV infusion on Day 1 of first treatment cycle (1 cycle = 21 days) at a loading dose of 840 mg, followed by 420 mg on Day 1 of each subsequent cycle; trastuzumab administered via SC injection at a dose of 600 mg on Day 2 of first treatment cycle, and on Day 1 of each subsequent cycle if both pertuzumab and trastuzumab were well tolerated in Cycle 1; and taxane treatment (docetaxel, paclitaxel, or nabpaclitaxel), administered at the discretion of the investigator, per routine clinical practices and local prescribing instructions. Participants continued study treatment until PD, unacceptable toxicity, or withdrawal of consent. Participants with unacceptable toxicity or PD were switched to standard treatment of the investigator's choice. All participants were followed-up until withdrawal of consent, loss to follow-up, death, or study closure.
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|---|---|
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Age, Continuous
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52.9 years
STANDARD_DEVIATION 12.0 • n=5 Participants
|
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Sex: Female, Male
Female
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49 Participants
n=5 Participants
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Sex: Female, Male
Male
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1 Participants
n=5 Participants
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PRIMARY outcome
Timeframe: Baseline up to 28 days after last study drug administration (up to 36 months)Population: Analysis was performed on the Safety population, which included all enrolled participants who received at least one dose of pertuzumab IV or trastuzumab SC.
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Percentage of participants with AEs and SAEs was reported. AEs included both SAEs and non-SAEs. The 95% confidence interval (CI) was computed using Clopper-Pearson method.
Outcome measures
| Measure |
Trastuzumab, Pertuzumab, and Taxane
n=50 Participants
Participants received first-line therapy with pertuzumab administered via IV infusion on Day 1 of first treatment cycle (1 cycle = 21 days) at a loading dose of 840 mg, followed by 420 mg on Day 1 of each subsequent cycle; trastuzumab administered via SC injection at a dose of 600 mg on Day 2 of first treatment cycle, and on Day 1 of each subsequent cycle if both pertuzumab and trastuzumab were well tolerated in Cycle 1; and taxane treatment (docetaxel, paclitaxel, or nabpaclitaxel), administered at the discretion of the investigator, per routine clinical practices and local prescribing instructions. Participants continued study treatment until PD, unacceptable toxicity, or withdrawal of consent. Participants with unacceptable toxicity or PD were switched to standard treatment of the investigator's choice. All participants were followed-up until withdrawal of consent, loss to follow-up, death, or study closure.
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|---|---|
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Percentage of Participants With Adverse Events (AEs) and Serious AEs
AEs
|
100.0 percentage of participants
Interval 92.9 to 100.0
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Percentage of Participants With Adverse Events (AEs) and Serious AEs
SAEs
|
54.0 percentage of participants
Interval 39.3 to 68.2
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PRIMARY outcome
Timeframe: Baseline up to 28 days after last study drug administration (up to 36 months)Population: Analysis was performed on the Safety population.
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Intensity of AEs were graded according to NCI CTCAE version 4.0 on a 5-point scale: Grade 1=Mild, intervention not indicated; Grade 2=Moderate, local or noninvasive intervention indicated; Grade 3=Severe or medically significant but not immediately life-threatening; Grade 4= Life-threatening consequences, urgent intervention indicated; and Grade 5=Death related to AE. Percentage of participants with AEs by maximum severity grades was reported.
Outcome measures
| Measure |
Trastuzumab, Pertuzumab, and Taxane
n=50 Participants
Participants received first-line therapy with pertuzumab administered via IV infusion on Day 1 of first treatment cycle (1 cycle = 21 days) at a loading dose of 840 mg, followed by 420 mg on Day 1 of each subsequent cycle; trastuzumab administered via SC injection at a dose of 600 mg on Day 2 of first treatment cycle, and on Day 1 of each subsequent cycle if both pertuzumab and trastuzumab were well tolerated in Cycle 1; and taxane treatment (docetaxel, paclitaxel, or nabpaclitaxel), administered at the discretion of the investigator, per routine clinical practices and local prescribing instructions. Participants continued study treatment until PD, unacceptable toxicity, or withdrawal of consent. Participants with unacceptable toxicity or PD were switched to standard treatment of the investigator's choice. All participants were followed-up until withdrawal of consent, loss to follow-up, death, or study closure.
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|---|---|
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Percentage of Participants With AEs by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0 Intensity Grades
Grade 1
|
4.0 percentage of participants
Interval 92.9 to 100.0
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|
Percentage of Participants With AEs by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0 Intensity Grades
Grade 2
|
32.0 percentage of participants
Interval 39.3 to 68.2
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|
Percentage of Participants With AEs by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0 Intensity Grades
Grade 3
|
50.0 percentage of participants
|
|
Percentage of Participants With AEs by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0 Intensity Grades
Grade 4
|
12.0 percentage of participants
|
|
Percentage of Participants With AEs by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0 Intensity Grades
Grade 5
|
2.0 percentage of participants
|
PRIMARY outcome
Timeframe: Baseline up to 28 days after last study drug administration (up to 36 months)Population: Analysis was performed on the Safety population.
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Percentage of participants with AEs leading to premature discontinuation of IMPs (pertuzumab and trastuzumab) was reported. AEs included both SAEs and non-SAEs. The 95% CI was computed using Clopper-Pearson method.
Outcome measures
| Measure |
Trastuzumab, Pertuzumab, and Taxane
n=50 Participants
Participants received first-line therapy with pertuzumab administered via IV infusion on Day 1 of first treatment cycle (1 cycle = 21 days) at a loading dose of 840 mg, followed by 420 mg on Day 1 of each subsequent cycle; trastuzumab administered via SC injection at a dose of 600 mg on Day 2 of first treatment cycle, and on Day 1 of each subsequent cycle if both pertuzumab and trastuzumab were well tolerated in Cycle 1; and taxane treatment (docetaxel, paclitaxel, or nabpaclitaxel), administered at the discretion of the investigator, per routine clinical practices and local prescribing instructions. Participants continued study treatment until PD, unacceptable toxicity, or withdrawal of consent. Participants with unacceptable toxicity or PD were switched to standard treatment of the investigator's choice. All participants were followed-up until withdrawal of consent, loss to follow-up, death, or study closure.
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Percentage of Participants With AEs Leading to Premature Discontinuation of Investigational Medicinal Products (IMPs)
|
12.0 percentage of participants
Interval 4.5 to 24.3
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PRIMARY outcome
Timeframe: Baseline up to 28 days after last study drug administration (up to 36 months)Population: Analysis was performed on the Safety population.
NYHA functional classification includes: Class I (no limitation in physical activity; ordinary physical activity does not cause fatigue, breathlessness or palpitation), Class II (slight limitation of physical activity; ordinary physical activity results in fatigue, palpitation, breathlessness or angina pectoris), Class III (marked limitation of physical activity; less than ordinary activity will lead to symptomatically 'moderate' heart failure) and Class IV (inability to carry out any physical activity without discomfort; symptoms of congestive cardiac failure are present even at rest). Percentage of participants with AEs suspected to be of cardiac origin by maximum NYHA classification was reported.
Outcome measures
| Measure |
Trastuzumab, Pertuzumab, and Taxane
n=50 Participants
Participants received first-line therapy with pertuzumab administered via IV infusion on Day 1 of first treatment cycle (1 cycle = 21 days) at a loading dose of 840 mg, followed by 420 mg on Day 1 of each subsequent cycle; trastuzumab administered via SC injection at a dose of 600 mg on Day 2 of first treatment cycle, and on Day 1 of each subsequent cycle if both pertuzumab and trastuzumab were well tolerated in Cycle 1; and taxane treatment (docetaxel, paclitaxel, or nabpaclitaxel), administered at the discretion of the investigator, per routine clinical practices and local prescribing instructions. Participants continued study treatment until PD, unacceptable toxicity, or withdrawal of consent. Participants with unacceptable toxicity or PD were switched to standard treatment of the investigator's choice. All participants were followed-up until withdrawal of consent, loss to follow-up, death, or study closure.
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Percentage of Participants With AEs of Suspected Cardiac Origin, by New York Heart Association Classification (NYHA)
Class I
|
6.0 percentage of participants
Interval 4.5 to 24.3
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|
Percentage of Participants With AEs of Suspected Cardiac Origin, by New York Heart Association Classification (NYHA)
Class II
|
4.0 percentage of participants
|
|
Percentage of Participants With AEs of Suspected Cardiac Origin, by New York Heart Association Classification (NYHA)
Class III
|
2.0 percentage of participants
|
|
Percentage of Participants With AEs of Suspected Cardiac Origin, by New York Heart Association Classification (NYHA)
Class IV
|
0.0 percentage of participants
|
PRIMARY outcome
Timeframe: Baseline up to 28 days after last study drug administration (up to 36 months)Population: Analysis was performed on the Safety population.
LVEF was assessed using echocardiography (ECHO) or multiple-gated acquisition (MUGA) scans. Percentage of participants with LVEF below 50% at any time during the study was reported.
Outcome measures
| Measure |
Trastuzumab, Pertuzumab, and Taxane
n=50 Participants
Participants received first-line therapy with pertuzumab administered via IV infusion on Day 1 of first treatment cycle (1 cycle = 21 days) at a loading dose of 840 mg, followed by 420 mg on Day 1 of each subsequent cycle; trastuzumab administered via SC injection at a dose of 600 mg on Day 2 of first treatment cycle, and on Day 1 of each subsequent cycle if both pertuzumab and trastuzumab were well tolerated in Cycle 1; and taxane treatment (docetaxel, paclitaxel, or nabpaclitaxel), administered at the discretion of the investigator, per routine clinical practices and local prescribing instructions. Participants continued study treatment until PD, unacceptable toxicity, or withdrawal of consent. Participants with unacceptable toxicity or PD were switched to standard treatment of the investigator's choice. All participants were followed-up until withdrawal of consent, loss to follow-up, death, or study closure.
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|---|---|
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Percentage of Participants With Left Ventricular Ejection Fraction (LVEF) Below 50%
|
8.0 percentage of participants
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SECONDARY outcome
Timeframe: Baseline up to withdrawal of consent, loss to follow-up, disease progression, death, or study end (up to approximately 36 months)Population: Analysis was performed on ITT population. Only participants with measurable disease at baseline were included in the analysis. Participants without a post-baseline tumor assessment were considered non-responders.
BOR was defined as a confirmed CR or PR. All measurable lesions up to a maximum of 2 lesions per organ and 5 in total were identified as target lesions (TLs) and recorded at baseline. A sum of the diameters (longest for non-nodal lesions, short axis \[SA\] for nodal lesions) for all TLs was calculated as baseline sum of diameters (SD). All other lesions (or sites of disease) were identified as non-TLs and were recorded at baseline. CR was defined as the disappearance of all TLs and SA reduction to less than (\<) 10 millimeter (mm) for nodal TLs/ non-TLs. PR was defined as greater than or equal to (\>/=) 30% decrease in SD of TLs, taking as reference the baseline SD. Confirmation of response at a consecutive tumor assessment at least 4 weeks apart was required. The 95% CI was computed using Clopper-Pearson method.
Outcome measures
| Measure |
Trastuzumab, Pertuzumab, and Taxane
n=45 Participants
Participants received first-line therapy with pertuzumab administered via IV infusion on Day 1 of first treatment cycle (1 cycle = 21 days) at a loading dose of 840 mg, followed by 420 mg on Day 1 of each subsequent cycle; trastuzumab administered via SC injection at a dose of 600 mg on Day 2 of first treatment cycle, and on Day 1 of each subsequent cycle if both pertuzumab and trastuzumab were well tolerated in Cycle 1; and taxane treatment (docetaxel, paclitaxel, or nabpaclitaxel), administered at the discretion of the investigator, per routine clinical practices and local prescribing instructions. Participants continued study treatment until PD, unacceptable toxicity, or withdrawal of consent. Participants with unacceptable toxicity or PD were switched to standard treatment of the investigator's choice. All participants were followed-up until withdrawal of consent, loss to follow-up, death, or study closure.
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|---|---|
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Percentage of Participants With Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
|
73.3 percentage of participants
Interval 58.1 to 85.4
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SECONDARY outcome
Timeframe: Baseline up to withdrawal of consent, loss to follow-up, disease progression, death, or study end (up to approximately 36 months)Population: Analysis was performed on the ITT population.
For TLs, PD was defined as \>/=20% relative increase and \>/=5 mm of absolute increase in the SD, taking as reference the smallest SD recorded since treatment started or the appearance of 1 or more new lesions. For non-TLs, PD was defined as appearance of 1 or more new lesions and/or unequivocal progression of existing non-TLs.
Outcome measures
| Measure |
Trastuzumab, Pertuzumab, and Taxane
n=50 Participants
Participants received first-line therapy with pertuzumab administered via IV infusion on Day 1 of first treatment cycle (1 cycle = 21 days) at a loading dose of 840 mg, followed by 420 mg on Day 1 of each subsequent cycle; trastuzumab administered via SC injection at a dose of 600 mg on Day 2 of first treatment cycle, and on Day 1 of each subsequent cycle if both pertuzumab and trastuzumab were well tolerated in Cycle 1; and taxane treatment (docetaxel, paclitaxel, or nabpaclitaxel), administered at the discretion of the investigator, per routine clinical practices and local prescribing instructions. Participants continued study treatment until PD, unacceptable toxicity, or withdrawal of consent. Participants with unacceptable toxicity or PD were switched to standard treatment of the investigator's choice. All participants were followed-up until withdrawal of consent, loss to follow-up, death, or study closure.
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|---|---|
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Percentage of Participants With PD (Assessed According to RECIST Version 1.1) or Death Due to Any Cause
|
60.0 percentage of participants
Interval 58.1 to 85.4
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SECONDARY outcome
Timeframe: Baseline up to withdrawal of consent, loss to follow-up, disease progression, death, or study end (up to approximately 36 months)Population: Analysis was performed on the ITT population.
PFS was defined as the time from start of treatment until first documented PD or death from any cause, whichever occurred first. Participants without PD, death, or who were lost to follow-up at the time of analysis were censored at the date of the last tumor assessment when non-progression was documented or at the last date of follow-up, whichever was last. Participants without tumor assessment data after the baseline were censored at baseline unless death occurred before first scheduled tumor assessment. PD was defined as \>/=20% relative increase and \>/=5 mm of absolute increase in the SD of TLs, taking as reference the smallest SD recorded since treatment started, and/or unequivocal progression of existing non-TLs, or appearance of 1 or more new lesions. Median PFS was estimated using Kaplan-Meier method. The 95% CI was computed using Brookmeyer and Crowley method.
Outcome measures
| Measure |
Trastuzumab, Pertuzumab, and Taxane
n=50 Participants
Participants received first-line therapy with pertuzumab administered via IV infusion on Day 1 of first treatment cycle (1 cycle = 21 days) at a loading dose of 840 mg, followed by 420 mg on Day 1 of each subsequent cycle; trastuzumab administered via SC injection at a dose of 600 mg on Day 2 of first treatment cycle, and on Day 1 of each subsequent cycle if both pertuzumab and trastuzumab were well tolerated in Cycle 1; and taxane treatment (docetaxel, paclitaxel, or nabpaclitaxel), administered at the discretion of the investigator, per routine clinical practices and local prescribing instructions. Participants continued study treatment until PD, unacceptable toxicity, or withdrawal of consent. Participants with unacceptable toxicity or PD were switched to standard treatment of the investigator's choice. All participants were followed-up until withdrawal of consent, loss to follow-up, death, or study closure.
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|---|---|
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Progression-free Survival (PFS) Assessed According to RECIST Version 1.1
|
17.02 months
Interval 12.48 to 31.18
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SECONDARY outcome
Timeframe: Baseline up to withdrawal of consent, loss to follow-up, disease progression, death, or study end (up to approximately 36 months)Population: Analysis was performed on the ITT population.
Percentage of participants who died due to any cause during the study was reported.
Outcome measures
| Measure |
Trastuzumab, Pertuzumab, and Taxane
n=50 Participants
Participants received first-line therapy with pertuzumab administered via IV infusion on Day 1 of first treatment cycle (1 cycle = 21 days) at a loading dose of 840 mg, followed by 420 mg on Day 1 of each subsequent cycle; trastuzumab administered via SC injection at a dose of 600 mg on Day 2 of first treatment cycle, and on Day 1 of each subsequent cycle if both pertuzumab and trastuzumab were well tolerated in Cycle 1; and taxane treatment (docetaxel, paclitaxel, or nabpaclitaxel), administered at the discretion of the investigator, per routine clinical practices and local prescribing instructions. Participants continued study treatment until PD, unacceptable toxicity, or withdrawal of consent. Participants with unacceptable toxicity or PD were switched to standard treatment of the investigator's choice. All participants were followed-up until withdrawal of consent, loss to follow-up, death, or study closure.
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|---|---|
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Percentage of Participants Who Died Due to Any Cause
|
18.0 percentage of participants
Interval 58.1 to 85.4
|
SECONDARY outcome
Timeframe: Baseline up to withdrawal of consent, loss to follow-up, disease progression, death, or study end (up to approximately 36 months)Population: Analysis was performed on the ITT population.
The OS was defined as the time from the start of treatment until death from any cause. Participants alive at the time of analysis and participants who were lost to follow-up were censored at their last clinical assessment date. Median OS was estimated using Kaplan-Meier method. The 95% CI was computed using Brookmeyer and Crowley method.
Outcome measures
| Measure |
Trastuzumab, Pertuzumab, and Taxane
n=50 Participants
Participants received first-line therapy with pertuzumab administered via IV infusion on Day 1 of first treatment cycle (1 cycle = 21 days) at a loading dose of 840 mg, followed by 420 mg on Day 1 of each subsequent cycle; trastuzumab administered via SC injection at a dose of 600 mg on Day 2 of first treatment cycle, and on Day 1 of each subsequent cycle if both pertuzumab and trastuzumab were well tolerated in Cycle 1; and taxane treatment (docetaxel, paclitaxel, or nabpaclitaxel), administered at the discretion of the investigator, per routine clinical practices and local prescribing instructions. Participants continued study treatment until PD, unacceptable toxicity, or withdrawal of consent. Participants with unacceptable toxicity or PD were switched to standard treatment of the investigator's choice. All participants were followed-up until withdrawal of consent, loss to follow-up, death, or study closure.
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|---|---|
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Overall Survival (OS)
|
NA months
Interval 31.28 to
Median and Upper Limit for 95% CI could not be estimated due to high number of censored participants.
|
SECONDARY outcome
Timeframe: Baseline up to withdrawal of consent, loss to follow-up, disease progression, death, or study end (up to approximately 36 months)Population: Analysis was performed on the ITT population.
EFS was defined as the time from the start of treatment until the first documented initiation of non-protocol-specified treatment for metastatic breast cancer, PD, or death from any cause, whichever occurred first. Participants without treatment change, PD, death, or who were lost to follow-up at the time of analysis were censored at the date of the last tumor assessment when non-progression was documented or at the last date of follow-up, whichever was last. Participants without tumor assessment after baseline were censored at baseline unless death occurred before first scheduled tumor assessment. PD was defined as \>/=20% relative increase and \>/=5 mm of absolute increase in the SD of TLs, taking as reference the smallest SD recorded since treatment started, and/or unequivocal progression of existing non-TLs, or appearance of 1 or more new lesions. Median EFS was estimated using Kaplan-Meier method. The 95% CI was computed using Brookmeyer and Crowley method.
Outcome measures
| Measure |
Trastuzumab, Pertuzumab, and Taxane
n=50 Participants
Participants received first-line therapy with pertuzumab administered via IV infusion on Day 1 of first treatment cycle (1 cycle = 21 days) at a loading dose of 840 mg, followed by 420 mg on Day 1 of each subsequent cycle; trastuzumab administered via SC injection at a dose of 600 mg on Day 2 of first treatment cycle, and on Day 1 of each subsequent cycle if both pertuzumab and trastuzumab were well tolerated in Cycle 1; and taxane treatment (docetaxel, paclitaxel, or nabpaclitaxel), administered at the discretion of the investigator, per routine clinical practices and local prescribing instructions. Participants continued study treatment until PD, unacceptable toxicity, or withdrawal of consent. Participants with unacceptable toxicity or PD were switched to standard treatment of the investigator's choice. All participants were followed-up until withdrawal of consent, loss to follow-up, death, or study closure.
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|---|---|
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Event-free Survival (EFS) Assessed According to RECIST Version 1.1
|
17.02 months
Interval 12.48 to 31.18
|
SECONDARY outcome
Timeframe: From start of second-line of treatment (any time from baseline up to 35 months) up to death due to any cause or study end (up to approximately 36 months)Population: Analysis was performed on the ITT population participants who started second-line of treatment.
Percentage of participants who died from any cause during second-line of treatment was reported.
Outcome measures
| Measure |
Trastuzumab, Pertuzumab, and Taxane
n=30 Participants
Participants received first-line therapy with pertuzumab administered via IV infusion on Day 1 of first treatment cycle (1 cycle = 21 days) at a loading dose of 840 mg, followed by 420 mg on Day 1 of each subsequent cycle; trastuzumab administered via SC injection at a dose of 600 mg on Day 2 of first treatment cycle, and on Day 1 of each subsequent cycle if both pertuzumab and trastuzumab were well tolerated in Cycle 1; and taxane treatment (docetaxel, paclitaxel, or nabpaclitaxel), administered at the discretion of the investigator, per routine clinical practices and local prescribing instructions. Participants continued study treatment until PD, unacceptable toxicity, or withdrawal of consent. Participants with unacceptable toxicity or PD were switched to standard treatment of the investigator's choice. All participants were followed-up until withdrawal of consent, loss to follow-up, death, or study closure.
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|---|---|
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Percentage of Participants Who Died During Receiving Second-Line of Treatment
|
30.0 percentage of participants
Interval 58.1 to 85.4
|
SECONDARY outcome
Timeframe: From start of second-line of treatment (any time from baseline up to 35 months) up to death due to any cause or study end (up to approximately 36 months)Population: Analysis was performed on the ITT population participants who started second-line of treatment.
The OS during second-line therapy was defined as the time from the start of second-line therapy (failure of first-line therapy) until death from any cause. Participants alive at the time of analysis and participants who were lost to follow-up were censored at their last clinical assessment date. Median OS during second-line therapy was estimated using Kaplan-Meier method. The 95% CI was computed using Brookmeyer and Crowley method.
Outcome measures
| Measure |
Trastuzumab, Pertuzumab, and Taxane
n=30 Participants
Participants received first-line therapy with pertuzumab administered via IV infusion on Day 1 of first treatment cycle (1 cycle = 21 days) at a loading dose of 840 mg, followed by 420 mg on Day 1 of each subsequent cycle; trastuzumab administered via SC injection at a dose of 600 mg on Day 2 of first treatment cycle, and on Day 1 of each subsequent cycle if both pertuzumab and trastuzumab were well tolerated in Cycle 1; and taxane treatment (docetaxel, paclitaxel, or nabpaclitaxel), administered at the discretion of the investigator, per routine clinical practices and local prescribing instructions. Participants continued study treatment until PD, unacceptable toxicity, or withdrawal of consent. Participants with unacceptable toxicity or PD were switched to standard treatment of the investigator's choice. All participants were followed-up until withdrawal of consent, loss to follow-up, death, or study closure.
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|---|---|
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OS During Second-Line of Treatment
|
21.29 months
Interval 14.85 to 29.04
|
SECONDARY outcome
Timeframe: Baseline up to approximately 35 monthsPopulation: Analysis was performed on the ITT population participants who started second-line of treatment.
Second-line anti-cancer treatment was initiated after disease progression on first-line therapy. Number of participants who started second-line of treatment by treatment type was reported. Participants who received combination treatment were counted for each treatment type.
Outcome measures
| Measure |
Trastuzumab, Pertuzumab, and Taxane
n=30 Participants
Participants received first-line therapy with pertuzumab administered via IV infusion on Day 1 of first treatment cycle (1 cycle = 21 days) at a loading dose of 840 mg, followed by 420 mg on Day 1 of each subsequent cycle; trastuzumab administered via SC injection at a dose of 600 mg on Day 2 of first treatment cycle, and on Day 1 of each subsequent cycle if both pertuzumab and trastuzumab were well tolerated in Cycle 1; and taxane treatment (docetaxel, paclitaxel, or nabpaclitaxel), administered at the discretion of the investigator, per routine clinical practices and local prescribing instructions. Participants continued study treatment until PD, unacceptable toxicity, or withdrawal of consent. Participants with unacceptable toxicity or PD were switched to standard treatment of the investigator's choice. All participants were followed-up until withdrawal of consent, loss to follow-up, death, or study closure.
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|---|---|
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Number of Participants Receiving Second-Line Treatment by Treatment Type
Capecitabine
|
8 participants
Interval 58.1 to 85.4
|
|
Number of Participants Receiving Second-Line Treatment by Treatment Type
Cyclophosphamide
|
2 participants
|
|
Number of Participants Receiving Second-Line Treatment by Treatment Type
Denosumab
|
2 participants
|
|
Number of Participants Receiving Second-Line Treatment by Treatment Type
Doxorubicin
|
1 participants
|
|
Number of Participants Receiving Second-Line Treatment by Treatment Type
Epirubicin
|
1 participants
|
|
Number of Participants Receiving Second-Line Treatment by Treatment Type
Eribulin
|
1 participants
|
|
Number of Participants Receiving Second-Line Treatment by Treatment Type
Fluorouracil
|
1 participants
|
|
Number of Participants Receiving Second-Line Treatment by Treatment Type
Lapatinib
|
4 participants
|
|
Number of Participants Receiving Second-Line Treatment by Treatment Type
Nanoparticle Paclitaxel
|
1 participants
|
|
Number of Participants Receiving Second-Line Treatment by Treatment Type
Paclitaxel
|
4 participants
|
|
Number of Participants Receiving Second-Line Treatment by Treatment Type
Pertuzumab
|
5 participants
|
|
Number of Participants Receiving Second-Line Treatment by Treatment Type
Trastuzumab
|
13 participants
|
|
Number of Participants Receiving Second-Line Treatment by Treatment Type
Trastuzumab Emtansine
|
10 participants
|
|
Number of Participants Receiving Second-Line Treatment by Treatment Type
Vinorelbine
|
1 participants
|
Adverse Events
Trastuzumab, Pertuzumab, and Taxane
Serious events: 27 serious events
Other events: 49 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Trastuzumab, Pertuzumab, and Taxane
n=50 participants at risk
Participants received first-line therapy with pertuzumab administered via IV infusion on Day 1 of first treatment cycle (1 cycle = 21 days) at a loading dose of 840 mg, followed by 420 mg on Day 1 of each subsequent cycle; trastuzumab administered via SC injection at a dose of 600 mg on Day 2 of first treatment cycle, and on Day 1 of each subsequent cycle if both pertuzumab and trastuzumab were well tolerated in Cycle 1; and taxane treatment (docetaxel, paclitaxel, or nabpaclitaxel), administered at the discretion of the investigator, per routine clinical practices and local prescribing instructions. Participants continued study treatment until PD, unacceptable toxicity, or withdrawal of consent. Participants with unacceptable toxicity or PD were switched to standard treatment of the investigator's choice. All participants were followed-up until withdrawal of consent, loss to follow-up, death, or study closure.
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|---|---|
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Blood and lymphatic system disorders
Febrile neutropenia
|
8.0%
4/50 • Baseline up to 28 days after last study drug administration (up to 36 months)
|
|
Blood and lymphatic system disorders
Anaemia
|
2.0%
1/50 • Baseline up to 28 days after last study drug administration (up to 36 months)
|
|
Blood and lymphatic system disorders
Neutropenia
|
2.0%
1/50 • Baseline up to 28 days after last study drug administration (up to 36 months)
|
|
Cardiac disorders
Cardiac failure
|
2.0%
1/50 • Baseline up to 28 days after last study drug administration (up to 36 months)
|
|
Gastrointestinal disorders
Diarrhoea
|
2.0%
1/50 • Baseline up to 28 days after last study drug administration (up to 36 months)
|
|
Gastrointestinal disorders
Gastritis
|
2.0%
1/50 • Baseline up to 28 days after last study drug administration (up to 36 months)
|
|
Gastrointestinal disorders
Nausea
|
2.0%
1/50 • Baseline up to 28 days after last study drug administration (up to 36 months)
|
|
Gastrointestinal disorders
Oesophagitis
|
2.0%
1/50 • Baseline up to 28 days after last study drug administration (up to 36 months)
|
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General disorders
Pyrexia
|
14.0%
7/50 • Baseline up to 28 days after last study drug administration (up to 36 months)
|
|
General disorders
Mucosal inflammation
|
2.0%
1/50 • Baseline up to 28 days after last study drug administration (up to 36 months)
|
|
Immune system disorders
Drug hypersensitivity
|
2.0%
1/50 • Baseline up to 28 days after last study drug administration (up to 36 months)
|
|
Infections and infestations
Cellulitis
|
4.0%
2/50 • Baseline up to 28 days after last study drug administration (up to 36 months)
|
|
Infections and infestations
Upper respiratory tract infection
|
4.0%
2/50 • Baseline up to 28 days after last study drug administration (up to 36 months)
|
|
Infections and infestations
Device related infection
|
2.0%
1/50 • Baseline up to 28 days after last study drug administration (up to 36 months)
|
|
Infections and infestations
Gastroenteritis
|
2.0%
1/50 • Baseline up to 28 days after last study drug administration (up to 36 months)
|
|
Infections and infestations
Sepsis
|
2.0%
1/50 • Baseline up to 28 days after last study drug administration (up to 36 months)
|
|
Infections and infestations
Urinary tract infection
|
2.0%
1/50 • Baseline up to 28 days after last study drug administration (up to 36 months)
|
|
Infections and infestations
Wound infection
|
2.0%
1/50 • Baseline up to 28 days after last study drug administration (up to 36 months)
|
|
Injury, poisoning and procedural complications
Femur fracture
|
2.0%
1/50 • Baseline up to 28 days after last study drug administration (up to 36 months)
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer
|
2.0%
1/50 • Baseline up to 28 days after last study drug administration (up to 36 months)
|
|
Nervous system disorders
Syncope
|
2.0%
1/50 • Baseline up to 28 days after last study drug administration (up to 36 months)
|
|
Psychiatric disorders
Anxiety
|
2.0%
1/50 • Baseline up to 28 days after last study drug administration (up to 36 months)
|
|
Psychiatric disorders
Depression
|
2.0%
1/50 • Baseline up to 28 days after last study drug administration (up to 36 months)
|
|
Psychiatric disorders
Psychotic disorder
|
2.0%
1/50 • Baseline up to 28 days after last study drug administration (up to 36 months)
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
4.0%
2/50 • Baseline up to 28 days after last study drug administration (up to 36 months)
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
2.0%
1/50 • Baseline up to 28 days after last study drug administration (up to 36 months)
|
|
Skin and subcutaneous tissue disorders
Dermatitis bullous
|
2.0%
1/50 • Baseline up to 28 days after last study drug administration (up to 36 months)
|
|
Skin and subcutaneous tissue disorders
Dermatomyositis
|
2.0%
1/50 • Baseline up to 28 days after last study drug administration (up to 36 months)
|
Other adverse events
| Measure |
Trastuzumab, Pertuzumab, and Taxane
n=50 participants at risk
Participants received first-line therapy with pertuzumab administered via IV infusion on Day 1 of first treatment cycle (1 cycle = 21 days) at a loading dose of 840 mg, followed by 420 mg on Day 1 of each subsequent cycle; trastuzumab administered via SC injection at a dose of 600 mg on Day 2 of first treatment cycle, and on Day 1 of each subsequent cycle if both pertuzumab and trastuzumab were well tolerated in Cycle 1; and taxane treatment (docetaxel, paclitaxel, or nabpaclitaxel), administered at the discretion of the investigator, per routine clinical practices and local prescribing instructions. Participants continued study treatment until PD, unacceptable toxicity, or withdrawal of consent. Participants with unacceptable toxicity or PD were switched to standard treatment of the investigator's choice. All participants were followed-up until withdrawal of consent, loss to follow-up, death, or study closure.
|
|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
8.0%
4/50 • Baseline up to 28 days after last study drug administration (up to 36 months)
|
|
Blood and lymphatic system disorders
Neutropenia
|
16.0%
8/50 • Baseline up to 28 days after last study drug administration (up to 36 months)
|
|
Cardiac disorders
Tachycardia
|
6.0%
3/50 • Baseline up to 28 days after last study drug administration (up to 36 months)
|
|
Eye disorders
Dry eye
|
12.0%
6/50 • Baseline up to 28 days after last study drug administration (up to 36 months)
|
|
Eye disorders
Lacrimation increased
|
8.0%
4/50 • Baseline up to 28 days after last study drug administration (up to 36 months)
|
|
Gastrointestinal disorders
Abdominal pain
|
10.0%
5/50 • Baseline up to 28 days after last study drug administration (up to 36 months)
|
|
Gastrointestinal disorders
Abdominal pain upper
|
6.0%
3/50 • Baseline up to 28 days after last study drug administration (up to 36 months)
|
|
Gastrointestinal disorders
Constipation
|
18.0%
9/50 • Baseline up to 28 days after last study drug administration (up to 36 months)
|
|
Gastrointestinal disorders
Diarrhoea
|
70.0%
35/50 • Baseline up to 28 days after last study drug administration (up to 36 months)
|
|
Gastrointestinal disorders
Dry mouth
|
6.0%
3/50 • Baseline up to 28 days after last study drug administration (up to 36 months)
|
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Gastrointestinal disorders
Dyspepsia
|
6.0%
3/50 • Baseline up to 28 days after last study drug administration (up to 36 months)
|
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Gastrointestinal disorders
Gastrooesophageal reflux disease
|
24.0%
12/50 • Baseline up to 28 days after last study drug administration (up to 36 months)
|
|
Gastrointestinal disorders
Nausea
|
46.0%
23/50 • Baseline up to 28 days after last study drug administration (up to 36 months)
|
|
Gastrointestinal disorders
Stomatitis
|
12.0%
6/50 • Baseline up to 28 days after last study drug administration (up to 36 months)
|
|
Gastrointestinal disorders
Vomiting
|
34.0%
17/50 • Baseline up to 28 days after last study drug administration (up to 36 months)
|
|
General disorders
Chest discomfort
|
6.0%
3/50 • Baseline up to 28 days after last study drug administration (up to 36 months)
|
|
General disorders
Chest pain
|
6.0%
3/50 • Baseline up to 28 days after last study drug administration (up to 36 months)
|
|
General disorders
Chills
|
8.0%
4/50 • Baseline up to 28 days after last study drug administration (up to 36 months)
|
|
General disorders
Fatigue
|
68.0%
34/50 • Baseline up to 28 days after last study drug administration (up to 36 months)
|
|
General disorders
Injection site reaction
|
6.0%
3/50 • Baseline up to 28 days after last study drug administration (up to 36 months)
|
|
General disorders
Mucosal inflammation
|
10.0%
5/50 • Baseline up to 28 days after last study drug administration (up to 36 months)
|
|
General disorders
Oedema peripheral
|
8.0%
4/50 • Baseline up to 28 days after last study drug administration (up to 36 months)
|
|
General disorders
Pain
|
6.0%
3/50 • Baseline up to 28 days after last study drug administration (up to 36 months)
|
|
Infections and infestations
Conjunctivitis
|
6.0%
3/50 • Baseline up to 28 days after last study drug administration (up to 36 months)
|
|
Infections and infestations
Nail infection
|
6.0%
3/50 • Baseline up to 28 days after last study drug administration (up to 36 months)
|
|
Infections and infestations
Oral candidiasis
|
8.0%
4/50 • Baseline up to 28 days after last study drug administration (up to 36 months)
|
|
Infections and infestations
Paronychia
|
14.0%
7/50 • Baseline up to 28 days after last study drug administration (up to 36 months)
|
|
Infections and infestations
Rash pustular
|
8.0%
4/50 • Baseline up to 28 days after last study drug administration (up to 36 months)
|
|
Infections and infestations
Sinusitis
|
8.0%
4/50 • Baseline up to 28 days after last study drug administration (up to 36 months)
|
|
Infections and infestations
Upper respiratory tract infection
|
38.0%
19/50 • Baseline up to 28 days after last study drug administration (up to 36 months)
|
|
Infections and infestations
Urinary tract infection
|
20.0%
10/50 • Baseline up to 28 days after last study drug administration (up to 36 months)
|
|
Investigations
Weight decreased
|
6.0%
3/50 • Baseline up to 28 days after last study drug administration (up to 36 months)
|
|
Metabolism and nutrition disorders
Decreased appetite
|
12.0%
6/50 • Baseline up to 28 days after last study drug administration (up to 36 months)
|
|
Metabolism and nutrition disorders
Hypocalcaemia
|
6.0%
3/50 • Baseline up to 28 days after last study drug administration (up to 36 months)
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
24.0%
12/50 • Baseline up to 28 days after last study drug administration (up to 36 months)
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
20.0%
10/50 • Baseline up to 28 days after last study drug administration (up to 36 months)
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
6.0%
3/50 • Baseline up to 28 days after last study drug administration (up to 36 months)
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
28.0%
14/50 • Baseline up to 28 days after last study drug administration (up to 36 months)
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
6.0%
3/50 • Baseline up to 28 days after last study drug administration (up to 36 months)
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
12.0%
6/50 • Baseline up to 28 days after last study drug administration (up to 36 months)
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
36.0%
18/50 • Baseline up to 28 days after last study drug administration (up to 36 months)
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
22.0%
11/50 • Baseline up to 28 days after last study drug administration (up to 36 months)
|
|
Nervous system disorders
Dizziness
|
18.0%
9/50 • Baseline up to 28 days after last study drug administration (up to 36 months)
|
|
Nervous system disorders
Dysgeusia
|
14.0%
7/50 • Baseline up to 28 days after last study drug administration (up to 36 months)
|
|
Nervous system disorders
Headache
|
34.0%
17/50 • Baseline up to 28 days after last study drug administration (up to 36 months)
|
|
Nervous system disorders
Lethargy
|
10.0%
5/50 • Baseline up to 28 days after last study drug administration (up to 36 months)
|
|
Nervous system disorders
Neuropathy peripheral
|
56.0%
28/50 • Baseline up to 28 days after last study drug administration (up to 36 months)
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
10.0%
5/50 • Baseline up to 28 days after last study drug administration (up to 36 months)
|
|
Psychiatric disorders
Anxiety
|
8.0%
4/50 • Baseline up to 28 days after last study drug administration (up to 36 months)
|
|
Psychiatric disorders
Depression
|
6.0%
3/50 • Baseline up to 28 days after last study drug administration (up to 36 months)
|
|
Psychiatric disorders
Insomnia
|
12.0%
6/50 • Baseline up to 28 days after last study drug administration (up to 36 months)
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
18.0%
9/50 • Baseline up to 28 days after last study drug administration (up to 36 months)
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
12.0%
6/50 • Baseline up to 28 days after last study drug administration (up to 36 months)
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea exertional
|
6.0%
3/50 • Baseline up to 28 days after last study drug administration (up to 36 months)
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
24.0%
12/50 • Baseline up to 28 days after last study drug administration (up to 36 months)
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
14.0%
7/50 • Baseline up to 28 days after last study drug administration (up to 36 months)
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
8.0%
4/50 • Baseline up to 28 days after last study drug administration (up to 36 months)
|
|
Skin and subcutaneous tissue disorders
Acne
|
8.0%
4/50 • Baseline up to 28 days after last study drug administration (up to 36 months)
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
54.0%
27/50 • Baseline up to 28 days after last study drug administration (up to 36 months)
|
|
Skin and subcutaneous tissue disorders
Dermatitis acneiform
|
6.0%
3/50 • Baseline up to 28 days after last study drug administration (up to 36 months)
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
16.0%
8/50 • Baseline up to 28 days after last study drug administration (up to 36 months)
|
|
Skin and subcutaneous tissue disorders
Erythema
|
8.0%
4/50 • Baseline up to 28 days after last study drug administration (up to 36 months)
|
|
Skin and subcutaneous tissue disorders
Nail disorder
|
24.0%
12/50 • Baseline up to 28 days after last study drug administration (up to 36 months)
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
14.0%
7/50 • Baseline up to 28 days after last study drug administration (up to 36 months)
|
|
Skin and subcutaneous tissue disorders
Rash
|
52.0%
26/50 • Baseline up to 28 days after last study drug administration (up to 36 months)
|
|
Skin and subcutaneous tissue disorders
Skin lesion
|
6.0%
3/50 • Baseline up to 28 days after last study drug administration (up to 36 months)
|
|
Surgical and medical procedures
Tooth extraction
|
6.0%
3/50 • Baseline up to 28 days after last study drug administration (up to 36 months)
|
|
Vascular disorders
Hot flush
|
14.0%
7/50 • Baseline up to 28 days after last study drug administration (up to 36 months)
|
|
Vascular disorders
Hypertension
|
12.0%
6/50 • Baseline up to 28 days after last study drug administration (up to 36 months)
|
|
Vascular disorders
Lymphoedema
|
6.0%
3/50 • Baseline up to 28 days after last study drug administration (up to 36 months)
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
- Publication restrictions are in place
Restriction type: OTHER