A Study to Evaluate the Efficacy and Safety of Pertuzumab + Trastuzumab + Docetaxel Versus Placebo + Trastuzumab + Docetaxel in Previously Untreated Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Metastatic Breast Cancer

Hoffmann-La Roche243 enrolled

Overview

This Phase III, randomized, double-blind, placebo-controlled, multicenter clinical trial in China will evaluate the efficacy and safety of pertuzumab + trastuzumab + docetaxel compared with placebo + trastuzumab + docetaxel in participants with previously untreated HER2-positive metastatic breast cancer.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

243

Conditions

Breast Cancer

Interventions

DocetaxelDRUG

Docetaxel (75-mg/m\^2) was administered by IV infusion every 3 weeks until disease progression or unacceptable toxicity.

PertuzumabDRUG

Pertuzumab (840-mg loading dose for Cycle 1, followed by 420 mg for subsequent cycles) was administered by IV infusion every 3 weeks until disease progression or unacceptable toxicity.

PlaceboDRUG

Placebo matched to pertuzumab was administered by IV infusion every 3 weeks until disease progression or unacceptable toxicity.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Histologically or cytologically confirmed adenocarcinoma of the breast with locally recurrent or metastatic disease that is suitable for chemotherapy * HER2-positive metastatic breast cancer (MBC) * Left ventricular ejection fraction (LVEF) greater than or equal to (\>=) 55 percent (%) at baseline (within 42 days of randomization) * Eastern Cooperative Oncology Group Performance Status of 0 or 1 * Women of childbearing potential and men should agree to use an effective form of contraception and to continue its use for the duration of study treatment and for at least 7 months after the last dose of study treatment (trastuzumab and/or pertuzumab) Exclusion Criteria: * History of anti-cancer therapy for MBC (with the exception of one prior hormonal regimen for MBC) * History of approved or investigative tyrosine kinase/HER inhibitors for breast cancer in any treatment setting, except trastuzumab used in the neoadjuvant or adjuvant setting * History of systemic breast cancer treatment in the neo-adjuvant or adjuvant setting with a disease-free interval from completion of the systemic treatment (excluding hormonal therapy) to metastatic diagnosis of less than (\<) 12 months * History of persistent Grade \>= 2 hematologic toxicity resulting from previous adjuvant therapy * Grade \>= 3 peripheral neuropathy at randomization * History of other malignancy within the last 5 years, except for carcinoma in situ of the cervix or non-melanoma skin carcinoma that has been previously treated with curative intent * Current clinical or radiographic evidence of central nervous system (CNS) metastases * History of exposure to cumulative doses of anthracyclines * Current uncontrolled hypertension or unstable angina * History of congestive heart failure (CHF) of any New York Heart Association (NYHA) classification, or serious cardiac arrhythmia requiring treatment * History of myocardial infarction within 6 months of randomization * History of LVEF decrease to \< 50% during or after prior trastuzumab neo-adjuvant or adjuvant therapy * Current dyspnea at rest due to complications of advanced malignancy, or other diseases that require continuous oxygen therapy * Inadequate organ function within 28 days prior to randomization * Current severe, uncontrolled systemic disease * Major surgical procedure or significant traumatic injury within 28 days prior to study treatment start or anticipation of the need for major surgery during the course of study treatment * Pregnant or lactating women * History of receiving any investigational treatment within 28 days of randomization * Current known infection with human immunodeficiency virus (HIV), hepatitis C virus (HCV), or active hepatitis B virus (HBV) * Receipt of intravenous (IV) antibiotics for infection within 14 days of randomization * Current chronic daily treatment with corticosteroids (excluding inhaled steroids) * Known hypersensitivity to any of the protocol-specified study treatments * Concurrent participation in an interventional or noninterventional study

Locations (15)

CHINESE ACADEMY OF MEDICAL SCIENCE; CANCER INST. & HOSPITAL; Medical ward

Beijing, China

Beijing Cancer Hospital

Beijing, China

Chinese PLA General Hospital

Outcomes

Primary Outcomes

Progression-Free Survival, as Determined by the Investigator Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)

Progression-free survival (PFS) was defined as the time from randomization to first occurrence of progressive disease (PD), as determined by the investigator using RECIST v1.1, or death from any cause within 18 weeks after the last tumor assessment, whichever occurred first. As per RECIST v1.1, PD is defined as a 20% increase in the sum of the diameters of target lesions, an increase in size of measurable lesions by at least 5 millimeters (mm), and the appearance of new lesions. The Kaplan-Meier approach was used to estimate median PFS for each treatment arm. Data for participants who did not have a PFS event were censored at the time of the last tumor assessment (if no tumor assessments performed after baseline, at randomization plus 1 day).

Time frame: From date of randomization until date of PFS event (Median [range] time on study for Arm A vs. Arm B at Primary analysis: 57.14 [3.3-93.3] weeks vs. 59.64 [0.9-90.4] weeks; Final analysis: 145.29 [3.3-225.3] weeks vs. 174.79 [0.9-226.1] weeks)

Kaplan-Meier Estimate of the Percentage of Participants Event-Free for Progression-Free Survival at 1 to 3 Years, as Determined by the Investigator Using RECIST v1.1

Progression-free survival (PFS) was defined as the time from randomization to first occurrence of progressive disease (PD), as determined by the investigator using RECIST v1.1, or death from any cause within 18 weeks after the last tumor assessment, whichever occurred first. As per RECIST v1.1, PD is a 20% increase in the sum of the diameters of target lesions, an increase in size of measurable lesions by at least 5 mm, and the appearance of new lesions. The Kaplan-Meier approach was used to estimate the percentage of participants who were event-free for PFS at 1, 2, and 3 years. Data for participants who did not have a PFS event were censored at the time of the last tumor assessment (if no tumor assessments performed after baseline visit, at randomization plus 1 day). At final analysis, the median \[range\] time on study for Arm A vs. Arm B was 145.29 \[3.3-225.3\] weeks vs. 174.79 \[0.9-226.1\] weeks.

Time frame: At 1, 2, and 3 years

Secondary Outcomes

Data from ClinicalTrials.gov

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Trastuzumab (8-mg/kg loading dose for Cycle 1, followed by 6 mg/kg for subsequent cycles) was administered by IV infusion every 3 weeks until disease progression or unacceptable toxicity.

the First Hospital of Jilin University

Changchun, China

Changzhou First People's Hospital

Changzhou, China

West China Hospital, Sichuan University

Chengdu, China

The 900th Hospital of PLA joint service support force

Fuzhou, China

Guangdong General Hospital

Guangzhou, China

Harbin Medical University Cancer Hospital

Harbin, China

Jiangsu province hospital; surgery on galactophore

Nanjing, China

...and 5 more locations

Overall survival (OS) was defined as the time from randomization to death from any cause. The Kaplan-Meier approach was used to estimate median OS for each treatment arm. Participants who were alive or lost to follow-up at the time of the analysis were censored at the date they were last known to be alive. Participants with no post-baseline information were censored at the time of randomization plus 1 day. The results reported here are from the final analysis. At the primary completion date, the median duration of OS had not been reached and OS data was not considered mature due to the few number of events reported.

Time frame: From date of randomization until the date of death from any cause (Median [range] time on study for Arm A vs. Arm B at Final analysis: 145.29 [3.3-225.3] weeks vs. 174.79 [0.9-226.1] weeks)

Kaplan-Meier Estimate of the Percentage of Participants Event-Free for Overall Survival at 1 to 3 Years

Overall survival (OS) was defined as the time from randomization to death from any cause. The Kaplan-Meier approach was used to estimate the percentage of participants who were event-free for OS (i.e., alive) at 1, 2, and 3 years. Participants who were alive or lost to follow-up at the time of the analysis were censored at the date they were last known to be alive. Participants with no post-baseline information were censored at the time of randomization plus 1 day. At final analysis, the median \[range\] time on study for Arm A vs. Arm B was 145.29 \[3.3-225.3\] weeks vs. 174.79 \[0.9-226.1\] weeks.

Time frame: At 1, 2, and 3 Years

Percentage of Participants With Measurable Disease at Baseline Who Achieved an Objective Response (Complete or Partial Response), as Determined by the Investigator Using RECIST v1.1

An objective response was defined as a complete response (CR) or partial response (PR), as determined by the investigator using RECIST v1.1. As per RECIST v1.1, CR is defined as the disappearance of all target lesions, and PR is defined as at least a 30% decrease in the sum of diameters of target lesions. Also per RECIST v1.1, stable disease (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 on study; PD is defined as a 20% increase in the sum of the diameters of target lesions, an increase in size of measurable lesions by at least 5 mm, and the appearance of new lesions. The same assessment technique must be used throughout the study for evaluating a particular lesion, and the same investigator should assess all tumor responses for each participant. Participants without a post-baseline tumor assessment were considered non-responders.

Time frame: At Baseline and every 9 weeks from date of randomization until disease progression or death, whichever occurs first (Median [range] time on study for Arm A vs. Arm B at Primary analysis: 57.14 [3.3-93.3] weeks vs. 59.64 [0.9-90.4] weeks)

Duration of Objective Response, as Determined by the Investigator Using RECIST v1.1

Duration of objective response was defined as the time from the first occurrence of a documented objective response (complete response \[CR\] or partial response \[PR\]) to the time of disease progression, as determined by the investigator using RECIST v1.1, or death from any cause within 18 weeks after the last tumor assessment, whichever occurred first. As per RECIST v1.1, CR is defined as the disappearance of all target lesions, and PR is defined as at least a 30% decrease in the sum of diameters of target lesions. The Kaplan-Meier approach was used to estimate median duration of objective response. Data for participants who did not have an event were censored at the time of the last tumor assessment (if no tumor assessments were performed after baseline visit, at randomization plus 1 day).

Time frame: From date of first occurrence of documented objective response to date of event (Median [range] time on study for Arm A vs. Arm B at Primary analysis: 57.14 [3.3-93.3] weeks vs. 59.64 [0.9-90.4] weeks)

Number of Participants With at Least One Adverse Event

The number of participants per treatment arm experiencing at least one adverse event, including all non-serious and serious adverse events, is reported here. Adverse events reported prior to first crossover treatment were included in the Placebo arm, and in the Crossover arm after that date, for participants in Arm A who crossed over from placebo to pertuzumab. At final analysis, the median \[range\] time on study treatment with placebo or pertuzumab per arm was: Arm A - Placebo: 52.3 \[3-207\] weeks; Arm B - Pertuzumab: 66.1 \[3-225\] weeks; Arm A - Crossover to Pertuzumab: 18.1 \[12-24\] weeks.