NCT00567190: CLEOPATRA

A Study to Evaluate Pertuzumab + Trastuzumab + Docetaxel vs. Placebo + Trastuzumab + Docetaxel in Previously Untreated HER2-Positive Metastatic Breast Cancer

Completed Phase 3 Results posted Last updated 13 December 2019

What this trial tests

Phase 3 trial testing Pertuzumab in Metastatic Breast Cancer in 808 participants. Completed in 23 November 2018.

Timeline

12 February 2008

Primary endpoint
13 May 2011

23 November 2018

Quick facts

Lead sponsor	Genentech, Inc.
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	triple
Primary purpose	treatment
Enrollment	808
Start date	12 February 2008
Primary completion	13 May 2011
Estimated completion	23 November 2018
Sites	322 locations across Hong Kong, Italy, Finland, Japan, Ecuador, Poland, South Korea, Philippines

Drugs / interventions tested

• Pertuzumab (pertuzumab) — full drug profile →
• Placebo
• Trastuzumab (trastuzumab) — full drug profile →
• Docetaxel (Docetaxel) — full drug profile →

Conditions studied

• Metastatic Breast Cancer — all drugs for Metastatic Breast Cancer →

Sponsor

Genentech, Inc. — full company profile →

Who can join

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

Results — posted to ClinicalTrials.gov

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

Progression-Free Survival (PFS) Determined by an Independent Review Facility Primary · Tumor assessments every 9 weeks from randomization to IRF-determined PD or death from any cause, whichever occurred first, up to the primary completion date (up to 3 years, 3 months)

PFS was defined as the time from randomization to first documented radiographical progressive disease (PD), as determined by an independent review facility (IRF) using RECIST version 1.0, or death from any cause (within 18 weeks of last tumor assessment), whichever occurred first (Kaplan-Meier method). For target lesions, PD was defined as at least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum of the LD recorded since treatment started or the appearance of ≥1 new lesion. For non-target lesions, PD was defined as the appearance of

Group	Value	95% CI
Pertuzumab + Trastuzumab + Docetaxel	18.5	15 – 23
Placebo + Trastuzumab + Docetaxel	12.4	10 – 13

Overall Survival Secondary · From randomization to death from any cause, up to each respective analysis data cut-off date (see the Description field for the median time on study per treatment arm)

Overall survival (OS) was the time from randomization to death from any cause, using Kaplan-Meier methodology. Survival data was collected every 18 weeks during the post-treatment follow-up period until death, loss to follow-up, or withdrawal of consent. Those who were alive, lost to follow up, or withdrew consent were censored at the latest date they participated in the study; those without post-baseline data were censored at 1 day. OS analyses were planned to take place at the primary completion date (First Interim), after 385 deaths (Event-Driven Final), and at the end of study (End-of-Stud

End-of-Study OS Analysis

Group	Value	95% CI
Pertuzumab + Trastuzumab + Docetaxel	57.1	50 – 72
Placebo + Trastuzumab + Docetaxel	40.8	36 – 48

Event-Driven Final OS Analysis

Group	Value	95% CI
Pertuzumab + Trastuzumab + Docetaxel	56.5	49 – NA
Placebo + Trastuzumab + Docetaxel	40.8	36 – 48

Second Interim OS Analysis

Group	Value	95% CI
Pertuzumab + Trastuzumab + Docetaxel	NA	42 – NA
Placebo + Trastuzumab + Docetaxel	37.6	34 – NA

First Interim OS Analysis

Group	Value	95% CI
Pertuzumab + Trastuzumab + Docetaxel	NA	NA – NA
Placebo + Trastuzumab + Docetaxel	NA	30 – NA

Progression-Free Survival (PFS) Determined by the Investigator Secondary · Tumor assessments every 9 weeks from randomization to investigator-determined PD or death from any cause, whichever occurred first (median [range] time on study in pertuzumab vs. placebo arms: 201.8 [0.7-520.0] weeks vs. 138.0 [0.4-514.7] weeks)

PFS was defined as the time from randomization to first documented radiographical progressive disease (PD), as determined by the investigator using RECIST version 1.0, or death from any cause (within 18 weeks of last tumor assessment), whichever occurred first (Kaplan-Meier method). For target lesions, PD was defined as at least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum of the LD recorded since treatment started or the appearance of ≥1 new lesion. For non-target lesions, PD was defined as the appearance of ≥1 new lesion or un

Group	Value	95% CI
Pertuzumab + Trastuzumab + Docetaxel	18.7	17 – 22
Placebo + Trastuzumab + Docetaxel	12.4	10 – 14

Objective Response Determined by an Independent Review Facility Secondary · Tumor assessments every 9 weeks from Baseline until IRF-determined progressive disease (PD), death, or first administration of next line of anti-cancer therapy (whichever occurred first), up to the primary completion date (up to 3 years, 3 months)

An objective response was defined as the percentage of participants with confirmed best overall response of complete response (CR) or partial response (PR) determined by an independent review facility (IRF) using RECIST v1.0 on two consecutive occasions ≥4 weeks apart. For target lesions, CR: disappearance of all target lesions; PR: ≥30% decrease in the sum of the longest diameter (LD) of target lesions (baseline sum LD as reference); PD: ≥20% increase in the sum of the LD of target lesions (smallest sum of the LD recorded as reference) or appearance of ≥1 new lesion; SD: neither sufficient sh

Objective Response (CR + PR)

Group	Value	95% CI
Pertuzumab + Trastuzumab + Docetaxel	80.2	75.6 – 84.3
Placebo + Trastuzumab + Docetaxel	69.3	64.1 – 74.2

Complete Response (CR)

Group	Value	95% CI
Pertuzumab + Trastuzumab + Docetaxel	5.5	3.4 – 8.5
Placebo + Trastuzumab + Docetaxel	4.2	2.3 – 6.9

Partial Response (PR)

Group	Value	95% CI
Pertuzumab + Trastuzumab + Docetaxel	74.6	69.7 – 79.2
Placebo + Trastuzumab + Docetaxel	65.2	59.8 – 70.3

Stable Disease (SD)

Group	Value	95% CI
Pertuzumab + Trastuzumab + Docetaxel	14.6	11.0 – 18.8
Placebo + Trastuzumab + Docetaxel	20.8	16.6 – 25.6

Progressive Disease (PD)

Group	Value	95% CI
Pertuzumab + Trastuzumab + Docetaxel	3.8	2.0 – 6.4
Placebo + Trastuzumab + Docetaxel	8.3	5.6 – 11.8

Unable to Assess (UA)

Group	Value	95% CI
Pertuzumab + Trastuzumab + Docetaxel	0.6	0.1 – 2.1
Placebo + Trastuzumab + Docetaxel	0.6	0.1 – 2.1

Missing (No Assessment)

Group	Value	95% CI
Pertuzumab + Trastuzumab + Docetaxel	0.9	NA – NA
Placebo + Trastuzumab + Docetaxel	0.9	NA – NA

Duration of Objective Response Determined by an Independent Review Facility Secondary · From initial IRF-confirmed objective response until IRF-determined progressive disease (PD), death, or first administration of next line of anti-cancer therapy (whichever occurred first), up to the primary completion date (up to 3 years, 3 months)

Duration of objective response (estimated using the Kaplan-Meier method) was defined as the time from the initial confirmed complete response (CR) or partial response (PR), the date of tumor assessment at which the CR/PR was first detected by the independent review facility (IRF) using RECIST version 1.0, until the date of IRF-determined progressive disease (PD), death from any cause within 18 weeks of the last tumor assessment, or first administration of next line of anti-cancer therapy (whichever occurred first). If the visit when the initial CR or PR was observed spanned multiple dates, the

Group	Value	95% CI
Pertuzumab + Trastuzumab + Docetaxel	87.6	71 – 106
Placebo + Trastuzumab + Docetaxel	54.1	46 – 64

Time to Symptom Progression Secondary · Every 9 weeks from Baseline until investigator-determined progressive disease, up to the primary completion date (up to 3 years, 3 months)

Time to symptom progression was defined as the time from randomization to the first symptom progression as measured by the Functional Assessment of Cancer Therapy-for patients with Breast Cancer (FACT-B) questionnaire with the Trial Outcomes Index-Physical/Functional/Breast (TOI-PFB) subscale. The FACT-B TOI-PFB subscale contains 24 items from 3 subsections of the FACT-B questionnaire: Physical well-being, functional well-being, and additional concerns for breast cancer patients (breast cancer subscale \[BCS\]). All items in the questionnaire were rated by the patient on a 5-point scale rangin

Group	Value	95% CI
Pertuzumab + Trastuzumab + Docetaxel	18.4	18 – 27
Placebo + Trastuzumab + Docetaxel	18.3	18 – 27

Overall Number of Participants Who Experienced at Least One Adverse Event, Including Serious and Non-Serious Adverse Events, by Most Severe Intensity (According to NCI-CTCAE v3.0) During the Treatment Period Secondary · Placebo arm: Baseline to last dose of study treatment +42 days (or crossover date); Pertuzumab arm: Baseline to last dose of study treatment +42 days; Crossover arm: Crossover date to last dose of study treatment +42 days (see Description - time per arm)

Adverse event (AE) severity was assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 3.0 (NCI-CTCAE v3.0); if the AE was not specifically listed, the following grades of severity were used: Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening or disabling; and Grade 5 = death. Severe and serious are not synonymous. Severity refers to the intensity of an AE, whereas a serious AE must meet criteria set out in the protocol; both were independently assessed for each AE. Only the most severe intensity was counted for

At Least One Serious AE - All Grades

Group	Value	95% CI
Placebo + Trastuzumab + Docetaxel	116
Pertuzumab + Trastuzumab + Docetaxel	160
Crossover From Placebo to Pertuzumab	10

At Least One Non-Serious AE - All Grades

Group	Value	95% CI
Placebo + Trastuzumab + Docetaxel	386
Pertuzumab + Trastuzumab + Docetaxel	400
Crossover From Placebo to Pertuzumab	45

At Least One AE - All Grades

Group	Value	95% CI
Placebo + Trastuzumab + Docetaxel	391
Pertuzumab + Trastuzumab + Docetaxel	408
Crossover From Placebo to Pertuzumab	47

At Least One AE - Grade 1

Group	Value	95% CI
Placebo + Trastuzumab + Docetaxel	368
Pertuzumab + Trastuzumab + Docetaxel	386
Crossover From Placebo to Pertuzumab	44

At Least One AE - Grade 2

Group	Value	95% CI
Placebo + Trastuzumab + Docetaxel	350
Pertuzumab + Trastuzumab + Docetaxel	383
Crossover From Placebo to Pertuzumab	34

At Least One AE - Grade 3

Group	Value	95% CI
Placebo + Trastuzumab + Docetaxel	229
Pertuzumab + Trastuzumab + Docetaxel	264
Crossover From Placebo to Pertuzumab	11

At Least One AE - Grade 4

Group	Value	95% CI
Placebo + Trastuzumab + Docetaxel	158
Pertuzumab + Trastuzumab + Docetaxel	167
Crossover From Placebo to Pertuzumab	1

At Least One AE - Grade 5

Group	Value	95% CI
Placebo + Trastuzumab + Docetaxel	12
Pertuzumab + Trastuzumab + Docetaxel	8
Crossover From Placebo to Pertuzumab	1

Overall Number of Adverse Events by Severity (NCI-CTCAE v3.0 All Grades and Grades 3 to 5) Per 100 Patient-Years of Exposure During the Treatment Period Secondary · From Baseline to 42 days after the last dose of study treatment (total patient-years of exposure on study treatment in Placebo vs. Pertuzumab arms: 526.81 vs. 989.88 patient-years)

Adverse event (AE) severity, including serious and non-serious AEs, was assessed according to the NCI-CTCAE version 3.0; if the AE was not specifically listed, the following grades of severity were used: Grade 1 is mild; Grade 2 is moderate; Grade 3 is severe; Grade 4 is life-threatening or disabling; and Grade 5 is death. Multiple occurrences of the same AE in 1 participant were counted multiple times. Only AEs that started during the overall study treatment period were included. The cutoff date for inclusion of events and for calculation of patient-years was the date of the most recent follo

All Grades

Group	Value	95% CI
Placebo + Trastuzumab + Docetaxel	1720.2	1690.6 – 1750.2
Pertuzumab + Trastuzumab + Docetaxel	1203.0	1184.9 – 1221.3

Grades 3 to 5

Group	Value	95% CI
Placebo + Trastuzumab + Docetaxel	225.3	214.7 – 236.4
Pertuzumab + Trastuzumab + Docetaxel	131.7	125.8 – 137.9

Cardiac-Related AEs to Monitor: Number of Participants Who Experienced at Least One Symptomatic Left Ventricular Dysfunction (LVD), Any LVD, or Serious AE Suggestive of Congestive Heart Failure by Severity During the Treatment Period Secondary · Placebo arm: Baseline to last dose of study treatment +42 days (or crossover date); Pertuzumab arm: Baseline to last dose of study treatment +42 days; Crossover arm: Crossover date to last dose of study treatment +42 days (see Description - time per arm)

Cardiac-related adverse events (AEs) to monitor during the study included investigator-assessed symptomatic left ventricular dysfunction (LVD), any LVD, or a serious adverse event (SAE) suggestive of congestive heart failure (CHF). All cardiac-related AEs were graded for severity according to NCI-CTCAE v3.0. Asymptomatic (Grades 1-2) and symptomatic (Grades 3-5) left ventricular systolic dysfunction (LVSD) both coded to the MedDRA preferred term LVD. Investigator-assessed events of symptomatic LVD were also graded for severity of symptoms according to Classes I (least severe) to IV (most sever

Symptomatic LVD(Investigator)-All NYHA Classes

Group	Value	95% CI
Placebo + Trastuzumab + Docetaxel	7
Pertuzumab + Trastuzumab + Docetaxel	6
Crossover From Placebo to Pertuzumab	1

Symptomatic LVD(Investigator)-NYHA Classes III/IV

Group	Value	95% CI
Placebo + Trastuzumab + Docetaxel	4
Pertuzumab + Trastuzumab + Docetaxel	4
Crossover From Placebo to Pertuzumab	1

Any LVD - All NCI-CTCAE Grades

Group	Value	95% CI
Placebo + Trastuzumab + Docetaxel	34
Pertuzumab + Trastuzumab + Docetaxel	32
Crossover From Placebo to Pertuzumab	3

Any LVD - NCI-CTCAE Grade ≥3

Group	Value	95% CI
Placebo + Trastuzumab + Docetaxel	13
Pertuzumab + Trastuzumab + Docetaxel	6
Crossover From Placebo to Pertuzumab	2

SAE Suggestive of CHF - All NCI-CTCAE Grades

Group	Value	95% CI
Placebo + Trastuzumab + Docetaxel	8
Pertuzumab + Trastuzumab + Docetaxel	8
Crossover From Placebo to Pertuzumab	1

SAE Suggestive of CHF - NCI-CTCAE Grade ≥3

Group	Value	95% CI
Placebo + Trastuzumab + Docetaxel	7
Pertuzumab + Trastuzumab + Docetaxel	7
Crossover From Placebo to Pertuzumab	1

Number of Participants Who Experienced at Least One Adverse Event to Monitor (Excluding Cardiac-Related AEs) by Severity During the Treatment Period Secondary · Placebo arm: Baseline to last dose of study treatment +42 days (or crossover date); Pertuzumab arm: Baseline to last dose of study treatment +42 days; Crossover arm: Crossover date to last dose of study treatment +42 days (see Description - time per arm)

The clinical diagnoses listed in this table, excluding cardiac safety (summarized separately), were also selected as adverse events (AEs) to monitor based on clinical and nonclinical data for pertuzumab and the safety profile established for trastuzumab, monoclonal antibodies in general, and potential effects associated with HER receptor inhibition. Search strategies were defined by single or aggregate MedDRA Preferred Terms (PT) through Standardized MedDRA Queries (SMQ), where possible, or based on Roche AE Group Terms (AEGT). Diarrhoea AEs: High-Level Term (HLT) 'Diarrhoea (excl. infective)'

Diarrhoea (HLT+PT) - All Grades

Group	Value	95% CI
Placebo + Trastuzumab + Docetaxel	191
Pertuzumab + Trastuzumab + Docetaxel	280
Crossover From Placebo to Pertuzumab	25

Diarrhoea (HLT+PT) - Grade ≥3

Group	Value	95% CI
Placebo + Trastuzumab + Docetaxel	20
Pertuzumab + Trastuzumab + Docetaxel	40
Crossover From Placebo to Pertuzumab	1

Rash (AEGT) - All Grades

Group	Value	95% CI
Placebo + Trastuzumab + Docetaxel	155
Pertuzumab + Trastuzumab + Docetaxel	213
Crossover From Placebo to Pertuzumab	18

Rash (AEGT) - Grade ≥3

Group	Value	95% CI
Placebo + Trastuzumab + Docetaxel	6
Pertuzumab + Trastuzumab + Docetaxel	15
Crossover From Placebo to Pertuzumab	0

Leukopenia (SMQ-narrow) - All Grades

Group	Value	95% CI
Placebo + Trastuzumab + Docetaxel	231
Pertuzumab + Trastuzumab + Docetaxel	257
Crossover From Placebo to Pertuzumab	1

Leukopenia (SMQ-narrow) - Grade ≥3

Group	Value	95% CI
Placebo + Trastuzumab + Docetaxel	211
Pertuzumab + Trastuzumab + Docetaxel	238
Crossover From Placebo to Pertuzumab	0

Leukopenic Infection (PTs) - All Grades

Group	Value	95% CI
Placebo + Trastuzumab + Docetaxel	38
Pertuzumab + Trastuzumab + Docetaxel	53
Crossover From Placebo to Pertuzumab	0

Leukopenic Infection (PTs) - Grade ≥3

Group	Value	95% CI
Placebo + Trastuzumab + Docetaxel	9
Pertuzumab + Trastuzumab + Docetaxel	18
Crossover From Placebo to Pertuzumab	0

Overall Number of Participants Who Experienced at Least One Adverse Event Leading to Discontinuation of Any or All Study Medication Secondary · Placebo arm: Baseline to last dose of study treatment +42 days (or crossover date); Pertuzumab arm: Baseline to last dose of study treatment +42 days; Crossover arm: Crossover date to last dose of study treatment +42 days (see Description - time per arm)

Participants could continue study treatment with pertuzumab/placebo plus trastuzumab when docetaxel was discontinued due to an adverse event (AE). Discontinuation of pertuzumab/placebo or trastuzumab due to an AE led to discontinuation of all study medication. The number of participants who discontinued any study medication due to an AE includes those who discontinued all study medication and those who discontinued docetaxel only and then continued on targeted therapy (note: some of these participants may have subsequently discontinued all treatment due to a separate AE). Multiple occurrences

AE Leading to Discontinuation-Any Study Medication

Group	Value	95% CI
Placebo + Trastuzumab + Docetaxel	114
Pertuzumab + Trastuzumab + Docetaxel	131
Crossover From Placebo to Pertuzumab	5

AE Leading to Discontinuation-All Study Medication

Group	Value	95% CI
Placebo + Trastuzumab + Docetaxel	24
Pertuzumab + Trastuzumab + Docetaxel	39
Crossover From Placebo to Pertuzumab	4

Overall Number of Participants Who Experienced at Least One Adverse Event That Resulted in Interruption or Modification of Any Study Medication Secondary · Placebo arm: Baseline to last dose of study treatment +42 days (or crossover date); Pertuzumab arm: Baseline to last dose of study treatment +42 days; Crossover arm: Crossover date to last dose of study treatment +42 days (see Description - time per arm)

Pertuzumab, trastuzumab, and docetaxel administration could have been delayed to assess or treat adverse events (AEs). Docetaxel dose reduction was allowed for myelosuppression, hepatic dysfunction, and other toxicities. No dose reduction was allowed for pertuzumab or trastuzumab. Multiple occurrences of the same adverse event in one participant was counted only once. AEs reported prior to first crossover treatment were included in the Placebo arm, and after that date in the Crossover arm, for participants who crossed over from placebo to pertuzumab. Median \[range\] time on study treatment pe

Group	Value	95% CI
Placebo + Trastuzumab + Docetaxel	217
Pertuzumab + Trastuzumab + Docetaxel	265
Crossover From Placebo to Pertuzumab	16

Adverse events — posted to ClinicalTrials.gov

Time frame: From first treatment dose (12-Feb-2008) through to end of study (23-Nov-2018) for a total safety analysis timeframe of 10 years, 9.5 months.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Placebo + Trastuzumab + Docetaxel

Serious: 116/396 (29%)

Deaths: 261/396

Pertuzumab + Trastuzumab + Docetaxel

Serious: 160/408 (39%)

Deaths: 238/408

Crossover From Placebo to Pertuzumab

Serious: 10/50 (20%)

Deaths: 14/50

Serious adverse events (179 terms)

Reaction	System	Placebo + Trastuzumab + Do…	Pertuzumab + Trastuzumab +…	Crossover From Placebo to …
Febrile neutropenia	Blood and lymphatic system disorders	—	—	—
Neutropenia	Blood and lymphatic system disorders	—	—	—
Diarrhoea	Gastrointestinal disorders	—	—	—
Pneumonia	Infections and infestations	—	—	—
Cellulitis	Infections and infestations	—	—	—
Left ventricular dysfunction	Cardiac disorders	—	—	—
Pyrexia	General disorders	—	—	—
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	—	—	—
Lower respiratory tract infection	Infections and infestations	—	—	—
Neutropenic infection	Infections and infestations	—	—	—
Pleural effusion	Respiratory, thoracic and mediastinal disorders	—	—	—
Anaemia	Blood and lymphatic system disorders	—	—	—
Atrial fibrillation	Cardiac disorders	—	—	—
Myocardial infarction	Cardiac disorders	—	—	—
Drug hypersensitivity	Immune system disorders	—	—	—
Hypersensitivity	Immune system disorders	—	—	—
Herpes zoster	Infections and infestations	—	—	—
Sepsis	Infections and infestations	—	—	—
Urinary tract infection	Infections and infestations	—	—	—
Femur fracture	Injury, poisoning and procedural complications	—	—	—
Deep vein thrombosis	Vascular disorders	—	—	—
Cardiac failure congestive	Cardiac disorders	—	—	—
Cataract	Eye disorders	—	—	—
Constipation	Gastrointestinal disorders	—	—	—
Intestinal perforation	Gastrointestinal disorders	—	—	—

Other adverse events (79 terms — click to expand)

Reaction	System	Placebo + Trastuzumab + Do…	Pertuzumab + Trastuzumab +…	Crossover From Placebo to …
Diarrhoea	Gastrointestinal disorders	—	—	—
Alopecia	Skin and subcutaneous tissue disorders	—	—	—
Neutropenia	Blood and lymphatic system disorders	—	—	—
Nausea	Gastrointestinal disorders	—	—	—
Fatigue	General disorders	—	—	—
Rash	Skin and subcutaneous tissue disorders	—	—	—
Asthenia	General disorders	—	—	—
Decreased appetite	Metabolism and nutrition disorders	—	—	—
Oedema peripheral	General disorders	—	—	—
Mucosal inflammation	General disorders	—	—	—
Vomiting	Gastrointestinal disorders	—	—	—
Headache	Nervous system disorders	—	—	—
Cough	Respiratory, thoracic and mediastinal disorders	—	—	—
Constipation	Gastrointestinal disorders	—	—	—
Anaemia	Blood and lymphatic system disorders	—	—	—
Myalgia	Musculoskeletal and connective tissue disorders	—	—	—
Nail disorder	Skin and subcutaneous tissue disorders	—	—	—
Neuropathy peripheral	Nervous system disorders	—	—	—
Upper respiratory tract infection	Infections and infestations	—	—	—
Arthralgia	Musculoskeletal and connective tissue disorders	—	—	—
Stomatitis	Gastrointestinal disorders	—	—	—
Leukopenia	Blood and lymphatic system disorders	—	—	—
Pyrexia	General disorders	—	—	—
Pain in extremity	Musculoskeletal and connective tissue disorders	—	—	—
Nasopharyngitis	Infections and infestations	—	—	—
Pruritus	Skin and subcutaneous tissue disorders	—	—	—
Dysgeusia	Nervous system disorders	—	—	—
Dizziness	Nervous system disorders	—	—	—
Dyspnoea	Respiratory, thoracic and mediastinal disorders	—	—	—
Insomnia	Psychiatric disorders	—	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—	—
Abdominal pain	Gastrointestinal disorders	—	—	—
Lacrimation increased	Eye disorders	—	—	—
Peripheral sensory neuropathy	Nervous system disorders	—	—	—
Dyspepsia	Gastrointestinal disorders	—	—	—
Hypertension	Vascular disorders	—	—	—
Muscle spasms	Musculoskeletal and connective tissue disorders	—	—	—
Oedema	General disorders	—	—	—
Dry skin	Skin and subcutaneous tissue disorders	—	—	—
Abdominal pain upper	Gastrointestinal disorders	—	—	—

Most-reported serious reactions: Febrile neutropenia, Neutropenia, Diarrhoea, Pneumonia, Cellulitis, Left ventricular dysfunction, Pyrexia, Pulmonary embolism.

Data from ClinicalTrials.gov NCT00567190 adverse events section.

Sponsor's own description

This study was a Phase III, randomized, double-blind, placebo-controlled, multicenter international clinical trial conducted to investigate the use of pertuzumab in combination with trastuzumab and docetaxel as first-line treatment for participants with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC). Participants could have received one prior hormonal treatment for MBC. Participants may have received systemic breast cancer treatment in the neo-adjuvant or adjuvant setting, provided that the participant had experienced a disease-free interval (DFI) of greater than or equal to (≥)12 months from completion of adjuvant systemic treatment (excluding hormonal therapy) to metastatic diagnosis. Participants may have received trastuzumab and/or a taxane during the neo-adjuvant or adjuvant treatment.

Participants were randomized in 1:1 ratio to receive either pertuzumab or placebo, along with trastuzumab and docetaxel once every 3 weeks (q3w), during the treatment phase of the study until investigator-assessed radiographic or clinical progressive disease, unmanageable toxicity, or study termination. Participants in the Placebo arm were not allowed to receive open-label pertuzumab after discontinuation from study treatment. However, if any analysis of overall survival had met the predefined criteria for statistical significance, participants in the Placebo arm still on treatment were offered the option to receive open-label pertuzumab in addition to other study medications.

Publications & conference data

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

1. Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer.
   Baselga J, Cortés J, Kim SB, Im SA, et al · · 2012 · cited 1788× · PMID 22149875 · DOI 10.1056/nejmoa1113216
2. Pertuzumab, trastuzumab, and docetaxel in HER2-positive metastatic breast cancer.
   Swain SM, Baselga J, Kim SB, Ro J, et al · · 2015 · cited 1504× · PMID 25693012 · DOI 10.1056/nejmoa1413513
3. Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA study): overall survival results from a randomised, double-blind, placebo-controlled, phase 3 study.
   Swain SM, Kim SB, Cortés J, Ro J, et al · · 2013 · cited 706× · PMID 23602601 · DOI 10.1016/s1470-2045(13)70130-x
4. Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA): end-of-study results from a double-blind, randomised, placebo-controlled, phase 3 study.
   Swain SM, Miles D, Kim SB, Im YH, et al · · 2020 · cited 657× · PMID 32171426 · DOI 10.1016/s1470-2045(19)30863-0
5. Neratinib Plus Capecitabine Versus Lapatinib Plus Capecitabine in HER2-Positive Metastatic Breast Cancer Previously Treated With ≥ 2 HER2-Directed Regimens: Phase III NALA Trial.
   Saura C, Oliveira M, Feng YH, Dai MS, et al · · 2020 · cited 441× · PMID 32678716 · DOI 10.1200/jco.20.00147
6. Tumour-infiltrating lymphocytes in advanced HER2-positive breast cancer treated with pertuzumab or placebo in addition to trastuzumab and docetaxel: a retrospective analysis of the CLEOPATRA study.
   Luen SJ, Salgado R, Fox S, Savas P, et al · · 2017 · cited 222× · PMID 27964843 · DOI 10.1016/s1470-2045(16)30631-3
7. PI3K inhibitors as new cancer therapeutics: implications for clinical trial design.
   Massacesi C, Di Tomaso E, Urban P, Germa C, et al · · 2016 · cited 171× · PMID 26793003 · DOI 10.2147/ott.s89967
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