Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Rare Diseases

Breast Neoplasms

Breast Diseases

Skin Diseases

Myotonic Dystrophy Type 1

Antineoplastic Agents

All Drugs and Chemicals

Anti-Arrhythmia Agents

Vasodilator Agents

Analgesics

Trastuzumab

Paclitaxel

Albumin-Bound Paclitaxel

Pertuzumab

Ado-Trastuzumab Emtansine

Maytansine

Adenosine

Tubulin Modulators

Antimitotic Agents

Antineoplastic Agents, Immunological

Immunotoxins

Immunoconjugates

Immunologic Factors

Participants received trastuzumab emtansine (T-DM1) every three weeks (Q3W) + paclitaxel weekly (QW) intravenously.

Participants received T-DM1 Q3W + paclitaxel QW + pertuzumab Q3W intravenously.

Participants received T-DM1 QW + paclitaxel QW intravenously.

Participants received T-DM1 QW + paclitaxel QW + pertuzumab Q3W intravenously.

Participants received maximum tolerated dose (MTD) from Phase 1b i.e. T-DM1 3.6mg/kg Q3W + paclitaxel 80mg/m\^2 QW intravenously.

Participants received MTD from Phase 1b i.e. T-DM1 3.6mg/kg Q3W + paclitaxel 80mg/m\^2 QW + pertuzumab Q3W intravenously.

paclitaxel

pertuzumab [Perjeta]

trastuzumab emtansine [Kadcyla]

Clinical Trials

This Phase Ib-IIa, multi-institutional, open-label, dose-escalation study is designed to evaluate the safety, tolerability, pharmacokinetics and feasibility of trastuzumab emtansine (T-DM1) administered by intravenous (IV) infusion in combination with paclitaxel (and pertuzumab, if applicable) in patients with human epidermal growth factor receptor 2-positive (HER2-positive), locally advanced or metastatic breast cancer.

A Study of Trastuzumab Emtansine, Paclitaxel, and Pertuzumab in Patients With HER2-Positive, Locally Advanced or Metastatic Breast Cancer

A Phase Ib-IIa, Open-label, Dose-Escalation Study of the Safety, Tolerability and Pharmacokinetics of Trastuzumab Emtansine, Paclitaxel and Pertuzumab Administered Intravenously to Patients With Her2-positive, Locally Advanced or Metastatic Breast Cancer

An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered to be related to the medicinal product. An SAE is any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or results in a congenital anomaly/birth defect.

DLT is defined as one of the following toxicities related to study drug during Cycle 1, according to the NCI CTCAE, Version 3: Grade 3 or higher non-hematologic AEs; Grade 3 or higher elevation of serum bilirubin, hepatic transaminases, or alkaline phosphatase; Grade 4 or higher thrombocytopenia; Grade 4 or higher neutropenia; any subjectively intolerable toxicity related to T-DM1, paclitaxel, or pertuzumab; any treatment-related toxicity prohibiting the start of the second cycle of treatment and/or prompting to a dose delay or modification during the DLT observation period, such as prompting a dose reduction at Cycle 2 Day1.

The MTD was defined as the highest dose of T-DM1 and paclitaxel at which 0 of 3 participants or 1 of 6 experienced a DLT, when T-DM1 (Q3W or QW) and paclitaxel (QW) was administered with and without pertuzumab treatment.

The MTD was defined as the highest dose of paclitaxel at which 0 of 3 participants or 1 of 6 experienced a DLT, when paclitaxel (QW) and T-DM1 (Q3W or QW) was administered with and without pertuzumab treatment.

Participants in Phase IIa received T-DM1 Q3W and paclitaxel in Group A and T-DM1, paclitaxel, and pertuzumab in Group B.

Participants were assessed for toxicity prior to each dose of T-DM1 and paclitaxel; dosing occurred only if the clinical assessment and laboratory test values were acceptable. Dose modifications included dose delayed or any dose reduction. Participants in whom significant toxicities had not recovered to the treatment range defined by the dose modification guidelines at the time of their next scheduled dose, had their dose of T-DM1 and/or paclitaxel delayed or reduced for up to 21 days.

Cmax of serum T-DM1 and total trastuzumab (sum of conjugated and unconjugated trastuzumab) in Cycle 1 was estimated by non-compartmental analysis for Phase Ib when T-DM1 was administered Q3W.

Cmax of plasma DM1 in Cycle 1 was estimated by non-compartmental analysis for Phase Ib when T-DM1 was administered Q3W.

AUC0-21 for serum T-DM1 and total trastuzumab (sum of conjugated and unconjugated trastuzumab) in Cycle 1 was estimated by non-compartmental analysis for Phase Ib when T-DM1 was administered Q3W.

Cmax for serum T-DM1 and total trastuzumab (sum of conjugated and unconjugated trastuzumab) in Cycle 1 was estimated by non-compartmental analysis when T-DM1 was administered QW.

Cmax for plasma DM1 in Cycle 1 was estimated by non-compartmental analysis for Phase Ib when T-DM1 was administered QW

AUClast for serum T-DM1 and serum total trastuzumab (sum of conjugated and unconjugated trastuzumab) in Cycle 1 was estimated by non-compartmental analysis for Phase Ib when T-DM1 was administered QW

Plasma Cmax of paclitaxel (65 mg/m\^2 and 80 mg/m\^2) for Cycle 1 (in the absence T-DM1) and Cycle 2 (in the presence T-DM1) was estimated by non-compartmental analysis.

Plasma AUC0-inf of paclitaxel (65 mg/m\^2 and 80 mg/m\^2) was estimated by non-compartmental analysis in Cycle 1 (in the absence T-DM1) and Cycle 2 (in the presence T-DM1).

Plasma t1/2 of paclitaxel (65 mg/m\^2 and 80 mg/m\^2) was estimated by non-compartmental analysis in Cycle 1 (in the absence T-DM1) and Cycle 2 (in the presence T-DM1).

Plasma CL of paclitaxel (65 mg/m\^2 and 80 mg/m\^2) was estimated by non-compartmental analysis for in Cycle 1 (in the absence T-DM1) and Cycle 2 (in the presence T-DM1).

Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Vss is the apparent volume of distribution at steady-state which is estimated by (D/AUC\[0-inf\]) X (AUMC\[0-inf\])/AUC\[0-inf\]) where D is the dose of study drug, AUMC(0-inf) is the area under the first moment curve extrapolated to infinity and AUC(0-inf) is the area under the plasma concentration-time curve from time zero to infinite time. The Vss of paclitaxel (65 mg/m2 and 80 mg/m2) is observed in Cycle 1 (in the absence of T-DM1) and Cycle 2 (in the presence of T-DM1).

Change in cardiac functions i.e., left ventricular ejection fraction (LVEF) and segmental wall abnormalities were assessed by echocardiogram or multigated acquisition scans. LVEF was assessed as change from baseline as 0 to \<15%, \>=15 to \<25%, \>=25%, and missing values.

Participants with measurable disease (at least one lesion 2 centimeters \[cm\] or more on computed tomography (CT) scan or 1 cm or more on spiral CT scan) were considered for OR. ORR is defined as the percentage of patients with a complete response (CR)/partial response (PR) determined on two consecutive tumor assessments at least 4 weeks apart based on modified Response Evaluation Criteria in Solid Tumors, Version 1.0 (RECIST). CR defined as disappearance of all target and non-target lesions and normalization of tumor marker level. PR defined as at least 30 percent decrease in sum of the longest diameters of the target lesions taking as reference the baseline sum longest diameters.

Duration of OR is only calculated for participants with OR and is defined as the time from the first tumor assessment that supports the participant's OR to disease progression or death.

Clinical benefit is defined as CR, PR, or stable disease (SD) of 6 months or more duration as assessed by the investigator. CR and PR are identified in previous outcome measure. SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum longest diameter since the treatment started. PD is defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of one or more new lesions.

PFS is defined as the time from the first day of study treatment to documented disease progression or death on study i.e., death due to any cause within 30-days of last dose of study treatment, whichever occurs first.

Genentech, Inc.

SAEs and other AEs were collected in the safety population, which was defined as all participants who received at least a single dose of study medication. There was one SAE that lead to death and the preferred term was not captured for it. The same SAE was captured as 'Death - unknown cause' in the below SAE table.

Participants received T-DM1 Q3W + paclitaxel QW intravenously.

Phase Ib Regimen 1

Phase Ib Regimen 2

Phase Ib Regimen 3

Phase Ib Regimen 4

Participants received MTD from Phase 1b i.e. T-DM1 3.6mg/kg Q3W and paclitaxel 80mg/m\^2 QW intravenously.

Phase IIa Group A

Participants received MTD from Phase 1b , i.e. T-DM1 3.6mg/kg Q3W and paclitaxel 80mg/m\^2 QW, plus pertuzumab Q3W intravenously.

Phase IIa Group B

Participants received MTD from Phase 1b i.e. T-DM1 3.6mg/kg Q3W + paclitaxel 80mg/m\^2 QW intravenously.

Participants received T-DM1 3.6mg/kg Q3W + paclitaxel 80mg/m\^2 QW + pertuzumab Q3W intravenously.

Total

Age, Continuous

Sex: Female, Male

Given the small sample size in the different patient subsets, no formal hypothesis testing was performed, and all statistical analyses should be considered descriptive and hypothesis-generating only.

Roche Trial Information Hotline

Any AEs

Any SAEs

Death

Any AEs Grade 3

Any AEs Grade 4

AEs leading to T-DM1 discontinuation

AEs leading to paclitaxel discontinuation

AEs leading to pertuzumab discontinuation

Safety Population: All participants who received at least a single dose of study medication were included.

Number of Participants With Any Adverse Events (AEs), Serious Adverse Events (SAEs), AEs of Grades 3/4, and Death

Safety Population: All participants of the dose finding part of the study (phase 1b) who received at least a single dose of study medication were included. Participants in Phase 1b (Regimen 1, Regimen 2, Regimen 3 and Regimen 4 \[60 participants\]) were considered for this analysis.

Number of Participants With Dose Limiting Toxicity (DLT) of the Combination of T-DM1 and Paclitaxel When T-DM1 Was Administered on Either an Q3W or QW Schedule for Both With and Without Pertuzumab Treatment

Safety Population: All participants of the dose finding part of the study (phase 1b) who received at least a single dose of study medication were included.

Maximum Tolerated Dose of T-DM1 When T-DM1 (Q3W or QW) and Paclitaxel (QW) Was Administered With and Without Pertuzumab

Maximum Tolerated Dose of Paclitaxel When T-DM1 (Q3W or QW) and Paclitaxel (QW) Was Administered With and Without Pertuzumab

Participants received MTD from Phase Ib i.e. T-DM1 3.6mg/kg Q3W and paclitaxel 80mg/m\^2 QW intravenously.

Participants received T-DM1 3.6mg/kg Q3W, paclitaxel 80mg/m\^2 QW, and pertuzumab 420 mg Q3W intravenously.

Safety Population: All participants of the phase IIa part of the study who received at least a single dose of study medication and did not have disease progression in the first 12 weeks of study treatment were included.

Number of Participants in Phase IIa of the Study Who Received 12 or More Paclitaxel Doses in Combination With T-DM1 and/or Pertuzumab

T-DM1

Participants received of T-DM1 3.6mg/kg Q3W, paclitaxel 80mg/m\^2 QW, and pertuzumab Q3W intravenously.

Number of Participants Who Had Adverse Events That Required Dose Modification of T-DM1 or Paclitaxel

Total trastuzumab

Participants received 2 mg/kg T-DM1 Q3W and 65 mg/m\^2 paclitaxel QW intravenously.

Phase Ib Cohort A

Participants received 2 mg/kg T-DM1 Q3W and 80 mg/m\^2 paclitaxel QW intravenously.

Phase Ib Cohort B

Participants received 2.4 mg/kg T-DM1 Q3W and 65 mg/m\^2 paclitaxel QW intravenously.

Phase Ib Cohort 1

Participants received 2.4 mg/kg T-DM1 Q3W and 80 mg/m\^2 paclitaxel QW intravenously.

Phase Ib Cohort J

Participants received 3.0 mg/kg T-DM1 Q3W and 80 mg/m\^2 paclitaxel QW intravenously.

Phase Ib Cohort D

Participants received 3.6 mg/kg T-DM1 Q3W and 80 mg/m\^2 paclitaxel QW intravenously.

Phase Ib Cohort 3B

Pharmacokinetics (PK) population included all participants from Phase Ib who received at least one dose of T-DM1 or paclitaxel with at least one post-dose concentration data point. Only participants with data available for this parameter were analyzed.

Maximum Serum Concentration (Cmax) of T-DM1 and Total Trastuzumab in Cycle 1 After Q3W Dose Regimen

PK population included all participants from Phase Ib who received at least one dose of T-DM1 or paclitaxel with at least one post-dose concentration data point. Only participants with data available for this parameter were analyzed.

Maximum Plasma Concentration (Cmax) of DM1 in Cycle 1 After Q3W Dose Regimen

Area Under the Serum Concentration-time Curve of Total Exposure (AUC0-Day 21) of T-DM1 and Total Trastuzumab in Cycle 1 After Q3W Dose Regimen

Participants received 1.2 mg/kg T-DM1 QW and 65 mg/m\^2 paclitaxel QW intravenously.

Phase Ib Cohort 6

Participants received 1.6 mg/kg T-DM1 QW and 65 mg/m\^2 paclitaxel QW intravenously.

Phase Ib Cohort 7

Participants received 2.0 mg/kg T-DM1 QW and 65 mg/m\^2 paclitaxel QW intravenously.

Phase Ib Cohort 8

Participants received 2.4 mg/kg T-DM1 QW and 65 mg/m\^2 paclitaxel QW intravenously.

Phase Ib Cohort F

Participants received 2.4 mg/kg T-DM1 QW and 80 mg/m\^2 paclitaxel QW intravenously.

Phase Ib Cohort 4

Maximum Serum Concentration (Cmax) of T-DM1 and Total Trastuzumab in Cycle 1 After QW Dose Regimen

Maximum Plasma Concentration (Cmax) of DM1 in Cycle 1 After QW Dose Regimen

Area Under the Serum Concentration-time Curve of Total Exposure (AUClast) of T-DM1 and Total Trastuzumab in Cycle 1 After QW Dose Regimen

65 mg, Cycle 1 (n = 29)

65 mg, Cycle 2 (n = 24)

80 mg, Cycle 1 (n = 18)

80 mg, Cycle 2 (n = 17)

For paclitaxel, plasma concentration-time data were available from 47 patients receiving administration of paclitaxel at QW doses of 65 and 80 mg/m\^2.

Phase Ib

PK population included all participants from Phase Ib who received at least one dose of T-DM1 or paclitaxel with at least one post-dose concentration data point. "n" denotes number of participants who received the indicated study drug.

Maximum Plasma Concentration of Paclitaxel in Cycle 1 (in the Absence T-DM1) and Cycle 2 (in the Presence T-DM1)

Area Under Plasma Concentration - Time Curve of Paclitaxel From Time 0 to Infinity (AUC0-inf) in Cycle 1 (in the Absence of T-DM1) and Cycle 2 (in the Presence of T-DM1)

An Elimination Half-life (t1/2) of Plasma Concentration of Paclitaxel in Cycle 1 (in the Absence of T-DM1) and Cycle 2 (in the Presence of T-DM1)

Plasma Clearance (CL) of Concentration of Paclitaxel in Cycle 1 (in the Absence of T-DM1) and Cycle 2 (in the Presence of T-DM1)

An Apparent Volume of Distribution at Steady-state (Vss) of Plasma Concentration of Paclitaxel in Cycle 1 (in the Absence of T-DM1) and Cycle 2 (in the Presence of T-DM1)

LVEF, increase

LVEF, 0 to <15%

LVEF, >=15 to <25%

LVEF, missing

New segmental wall abnormality

Number of Participants With Change From Baseline in Cardiac Function

An efficacy population: All participants who received at least a single dose of study medication were included. Participants with measurable disease were considered for OR.

Percentage of Participants With Objective Response Rate (ORR)

An efficacy population: All participants who received at least a single dose of study medication were included. Participants with OR were considered for this outcome measure.

Duration of Objective Response

An efficacy population: All participants who received at least a single dose of study medication were included.

Percentage of Participants With Clinical Benefit

Progression-free Survival (PFS)

Phase 1b

Phase 2a

Symptoms and General Pathology

Neoplasm Metastasis

Neoplastic Processes

Docetaxel

Patients received trastuzumab emtansine 3.6 mg/kg intravenously (IV) administered over 30-90 minutes every 3 weeks on Day 1 of each 21-day cycle.

Patients received a loading dose of trastuzumab 8 mg/kg IV + docetaxel 75 or 100 mg/m\^2 IV on Day 1 of Cycle 1 followed by trastuzumab 6 mg/kg IV + docetaxel 75 or 100 mg/m\^2 IV on Day 1 of all subsequent 21-day cycles.

The total dose depended on the patient's weight on Day 1 of each cycle. Trastuzumab emtansine was administered every 3 weeks until investigator-assessed radiographic or clinical progressive disease (or until second disease progression for patients who crossed over), unacceptable toxicity, or study closure, whichever occurred first.

Trastuzumab emtansine [Kadcyla]

The dose of trastuzumab was recalculated if body weight changed by more than ±10% from baseline. Trastuzumab was administered every 3 weeks until investigator-assessed radiographic or clinical progressive disease, or unmanageable toxicity. Patients in the trastuzumab + docetaxel arm who discontinued study treatment because of progressive disease were eligible to cross-over to trastuzumab emtansine treatment until a second progressive disease event, clinical deterioration, and/or intolerance.

Docetaxel was given at a dose of 75 or 100 mg/m\^2 based on the investigator's decision. Patients in the trastuzumab + docetaxel arm who discontinued study treatment because of progressive disease were eligible to cross-over to trastuzumab emtansine treatment until a second progressive disease event, clinical deterioration, and/or intolerance.

Ellie Guardino, MD/PhD

This was a Phase II, randomized, multicenter, international, 2-arm, open-label clinical trial designed to explore the efficacy and safety of trastuzumab emtansine (T-DM1) relative to the combination of trastuzumab and docetaxel in patients with human epidermal growth factor receptor 2 (HER2)-positive, unresectable, locally advanced breast cancer and/or metastatic breast cancer who have not received prior chemotherapy for metastatic disease.

A Study of the Efficacy and Safety of Trastuzumab Emtansine (Trastuzumab-MCC-DM1) vs. Trastuzumab (Herceptin®) and Docetaxel (Taxotere®) in Patients With Metastatic HER2-positive Breast Cancer Who Have Not Received Prior Chemotherapy for Metastatic Disease

A Randomized, Multicenter, Phase ii Study of the Efficacy and Safety of Trastuzumab-MCC-DM1 vs. Trastuzumab (Herceptin®) and Docetaxel (Taxotere®) in Patients With Metastatic HER2-positive Breast Cancer Who Have Not Received Prior Chemotherapy for Metastatic Disease

PFS was defined as the time from randomization (R) to first documented investigator-assessed radiographic or clinical disease progression (PD) or death due to any cause, whichever occurred first. For target lesions (TL), PD was defined as at least a 20% increase in the sum of the longest diameter (SLD) of TLs, taking as reference the SLD recorded since treatment started or the appearance of 1 or more new lesions. For non-TLs, PD was defined as the appearance of 1 or more new lesions and/or unequivocal progression of existing non-TLs. Data for patients without PD or death were censored at the last date of tumor assessment prior to crossover (or, if no tumor assessment was performed after Baseline, at the R date +1 day). Data for patients who were lost to follow-up were censored at the last date of tumor assessment prior to crossover at which the patient was known to be progression free. Data for patients with no post-baseline tumor assessment were censored at the R date +1 day.

Overall survival was defined as the time from randomization to the date of death from any cause. Patients who were alive at the time of analysis were censored at the date on which they were last known to be alive. Patients with no post-baseline were censored at the date of randomization plus 1 day.

A patient had an objective response if they had a complete response or a partial response on 2 consecutive occasions ≥ 4 weeks apart. For target lesions, a complete response was defined as the disappearance of all target lesions; a partial response was defined as at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter. For non-target lesions, a complete response was defined as the disappearance of all non-target lesions; a partial response was defined as the persistence of 1 or more non-target lesions.

Duration of objective response was defined as the time from initial response to investigator-assessed radiographic or clinical disease progression or death on study from any cause. For target lesions, disease progression was defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum of the longest diameter recorded since treatment started or the appearance of 1 or more new lesions. For non-target lesions, disease progression was defined as the appearance of 1 or more new lesions and/or unequivocal progression of existing non-target lesions. Target lesions should be selected on the basis of their size (those with the longest diameter) and their suitability for accurate repeated measurements by imaging techniques or clinically. All measurable lesions up to a maximum of 5 lesions per organ and 10 lesions in total, representative of all involved organs, should be identified as target lesions.

CB was defined as an objective response (complete response \[CR\], partial response \[PR\]) or stable disease (SD) for 6 months after randomization. For target lesions (TL), CR=the disappearance of all TL; PR=at least a 30% decrease in the sum of the longest diameter (LD) of TL, taking as reference the baseline sum LD; SD=neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum LD since the treatment started; PD=at least a 20% increase in the sum of the LD of TL, taking as reference the smallest sum of the LD recorded since the treatment started or the appearance of 1 or more new lesions. For non-TL, CR=the disappearance of all non-TL; PR=the persistence of 1 or more non-TL; SD=the persistence of 1 or more non-target lesion(s) and/or the maintenance of tumor marker level above the normal limits; PD=the appearance of 1 or more new lesions and/or unequivocal progression of existing non-TL.

Time to symptom progression was defined as the time from randomization to the first documentation of a ≥ 5-point decrease from baseline in the Trial Outcome Index-Physical/Functional/Breast (TOI-PFB) subscale score of the Functional Assessment of Cancer Therapy-Breast (FACT-B) questionnaire. The FACT-B questionnaire is a valid and reliable measure of symptoms associated with breast cancer. The TOI-PFB is a 24-item subscale generated using 3 subsections (Physical Well-Being \[7 items\], Functional Well-Being \[7 items\], and Additional Concerns \[10 items\]) from the FACT-B questionnaire. Patients responded to each item on a scale of 0-4 (Not at all-Very much). The total score ranged from 0 to 96. A higher score indicates fewer symptoms. A positive change score indicates improvement.

Serum samples were collected from all 67 patients enrolled in the trastuzumab emtansine arm using sparse pharmacokinetic sampling. Blood samples were collected prior to dosing and 30 minutes post-infusion of trastuzumab emtansine at Cycles 1 and 5. Serum samples were assayed for trastuzumab emtansine and total trastuzumab (sum of unconjugated trastuzumab and emtansine conjugated to trastuzumab) in indirect sandwich ELISAs. The area under the concentration-time curve (AUC) was estimated based on non-compartmental analysis using WinNonlin (Version 5.2.1) software.

Plasma samples were collected from all 67 patients in the trastuzumab emtansine group 30 minutes post-infusion of trastuzumab emtansine at Cycles 1 and 5. The plasma samples were assayed for free emtansine in a mass-spectrometric assay.

Hoffmann-La Roche

Safety population: All randomized patients who received at least 1 dose of study treatment. In the trastuzumab + docetaxel (T+D) group, 2 patients received no treatment and 2 patients received a dose of trastuzumab emtansine (TE) and were included in that group for safety analyses, resulting in 66 patients in the T+D group and 69 in the TE group.

Trastuzumab Emtansine

Trastuzumab + Docetaxel

Medical Communications

Intent-to-treat population: All randomized patients.

Progression-free Survival (PFS) by the Investigator Using Modified Response Evaluation Criteria In Solid Tumors (RECIST)

Overall Survival

All randomized patients with measureable disease at Baseline.

Objective Response Assessed by the Investigator Using Response Evaluation Criteria in Solid Tumors (RECIST)

All randomized patients with measureable disease at Baseline. Only patients with an objective response were included in the analysis.

Duration of Objective Response Assessed by the Investigator Using Response Evaluation Criteria in Solid Tumors (RECIST)

All randomized patients with measurable disease at Baseline.

Clinical Benefit (CB) Assessed by the Investigator Using Response Evaluation Criteria in Solid Tumors (RECIST)

All randomized patients with a Baseline and at least 1 post-Baseline valid score.

Time to Symptom Progression

Trastuzumab emtansine Cycle 1 (n=62)

Trastuzumab emtansine Cycle 5 (n=39)

Total trastuzumab Cycle 1 (n=60)

Total trastuzumab Cycle 5 (n=38)

Pharmacokinetic evaluable population: Patients who had adequate concentration-time data to estimate at least 1 pharmacokinetic parameter.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study of Trastuzumab Emtansine, Paclitaxel, and Pertuzumab in Patients With HER2-Positive, Locally Advanced or Metastatic Breast Cancer	NCT00951665	Metastatic Brea...	paclitaxel pertuzumab [Per... trastuzumab emt... paclitaxel trastuzumab emt...	18 Years -	Genentech, Inc.
A Study of the Efficacy and Safety of Trastuzumab Emtansine (Trastuzumab-MCC-DM1) vs. Trastuzumab (Herceptin®) and Docetaxel (Taxotere®) in Patients With Metastatic HER2-positive Breast Cancer Who Have Not Received Prior Chemotherapy for Metastatic Disease	NCT00679341	Breast Cancer	Trastuzumab emt... Trastuzumab Docetaxel	18 Years -	Hoffmann-La Roche
Corrected QT Interval Effects of Trastuzumab Emtansine (T-DM1) in Patients With Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Locally Advanced or Metastatic Breast Cancer and the Safety and Tolerability of Combined T-DM1 and Pertuzumab in Patients With Early Disease Progression	NCT00943670	Metastatic Brea...	pertuzumab Trastuzumab emt...	18 Years -	Genentech, Inc.

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