Clinical trialPhase 3Breast cancer

Pertuzumab plus Trastuzumab plus Docetaxel for Metastatic Breast Cancer

N Engl J Med · 2012808 patients

Baselga J, Cortés J, Kim SB, Im SA, Hegg R, Im YH, et al. N Engl J Med. 2012. 366:109-119

A newer report of this study has been published: Pertuzumab, Trastuzumab, and Docetaxel in HER2-Positive Metastatic Breast Cancer (2015)

Study type: Clinical trial
Study name: CLEOPATRA
Phase: Phase 3
Design: Randomised, placebo-controlled trial
Sample size: 808 patients
Source: N Engl J Med · 2012
Trial registration: NCT00567190

In plain words

In this study, women with advanced HER2-positive breast cancer were given, in addition to the drugs trastuzumab and docetaxel, either the drug pertuzumab or a placebo (dummy drug). Adding pertuzumab meant the disease got worse a median of about 6 months later (18.5 months versus 12.4 months). Heart problems did not increase, but low white blood cells with fever and severe diarrhoea were more common in the pertuzumab group.

Key results

18.5 months vs 12.4 months (pertuzumab group vs control)

Median progression-free survival (independent assessment)

HR for progression or death 0.62; 95% CI 0.51–0.75; P<0.001

Strong trend in favour of pertuzumab plus trastuzumab and docetaxel

Overall survival (interim analysis)

Interim analysis

Drugs in this study:Docetaxel (Taxotere)Pertuzumab (Perjeta)Trastuzumab (Herceptin)

Dose and schedule cards

THP (pertuzumab + trastuzumab + docetaxel; CLEOPATRA)

HER2-positive metastatic disease, first-line (no prior anti-HER2 therapy or chemotherapy for metastatic disease)Cycle length: Every 21 daysOn the page “Breast cancer” · Advanced HER2-positive and HER2-low disease

HER2-positive metastatic disease, first-line (no prior anti-HER2 therapy or chemotherapy for metastatic disease)

Drug	Dose	Route	Schedule
Pertuzumab	Loading dose 840 mg, then 420 mg	IV	Day 1
Trastuzumab	Loading dose 8 mg/kg, then 6 mg/kg	IV	Day 1
At least 6 cycles
Docetaxel	75 mg/m² (up to 100 mg/m² if tolerated)	IV	Day 1

Cycle length: Every 21 days
Duration: Docetaxel for at least 6 cycles; pertuzumab and trastuzumab until progression or unacceptable toxicity

Baseline LVEF of at least 50%, monitored about every 12 weeks; LVEF below 40%, or 40 to 45% with a decrease of 10 points or more: withhold for at least 3 weeks. NCCN (version 4.2026) considers THP the preferred first-line approach for most patients.

On the page “Breast cancer” · Advanced HER2-positive and HER2-low disease

THP — pertuzumab + trastuzumab + docetaxel (CLEOPATRA)

HER2-positive metastatic breast cancer, first line (no previous anti-HER2 therapy or chemotherapy for metastatic disease)Cycle length: Every 3 weeksOn the page “Pertuzumab (Perjeta)” · Standard doses: with trastuzumab and chemotherapy (FDA label)

HER2-positive metastatic breast cancer, first line (no previous anti-HER2 therapy or chemotherapy for metastatic disease)

Drug	Dose	Route	Schedule
Pertuzumab	Initial dose 840 mg, then 420 mg	IV infusion; initial 60 minutes, then 30 to 60 minutes	Day 1 every 3 weeks
Trastuzumab	Initial dose 8 mg/kg, then 6 mg/kg (or subcutaneous 600 mg fixed dose)	IV; initial 90 minutes, then 30 to 90 minutes	Day 1 every 3 weeks
Docetaxel	75 mg/m² (up to 100 mg/m² if tolerated)	IV, after pertuzumab and trastuzumab	Day 1 every 3 weeks

Cycle length: Every 3 weeks
Duration: Until disease progression or unacceptable toxicity

On the page “Pertuzumab (Perjeta)” · Standard doses: with trastuzumab and chemotherapy (FDA label)

Doses follow the trial protocol, guideline or official drug label (source given in the notes of each regimen). Before prescribing, check blood counts, renal and hepatic function, drug interactions and the patient’s condition, and adjust the dose according to the drug label.

Treatment arms and regimens

1Control group

Placebo plus trastuzumab plus docetaxel as first-line treatment until disease progression or the development of toxic effects that could not be effectively managed.

Placebo every 3 weeks + trastuzumab loading dose 8 mg/kg then 6 mg/kg every 3 weeks + docetaxel 75 mg/m² every 3 weeks (could be escalated to 100 mg/m²) for at least 6 cycles.

2Pertuzumab group

Pertuzumab plus trastuzumab plus docetaxel as first-line treatment until disease progression or the development of toxic effects that could not be effectively managed.

Pertuzumab loading dose 840 mg then 420 mg IV every 3 weeks + trastuzumab (8 then 6 mg/kg) + docetaxel 75 mg/m² every 3 weeks (could be escalated to 100) for at least 6 cycles.

Source of the regimen details: ClinicalTrials.gov NCT00567190 and the FDA label for Perjeta (DailyMed, section 14.1)

Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.

Study population

Patients with HER2-positive metastatic breast cancer receiving first-line treatment for metastatic disease.

Endpoints

Primary endpoint: progression-free survival (PFS) by independent assessment. Secondary endpoints: overall survival, investigator-assessed PFS, objective response rate and safety.

Safety and side effects

The safety profile was generally similar in the two groups, and no increase in left ventricular systolic dysfunction was seen. Rates of febrile neutropenia and grade 3 or higher diarrhoea were higher in the pertuzumab group than in the control group.

Clinical significance and place in guidelines

This study showed that adding pertuzumab to trastuzumab and docetaxel in first-line treatment of HER2-positive metastatic breast cancer significantly prolongs progression-free survival without increasing cardiac toxicity. The abstract gives no information on drug approvals or formal guideline recommendations, and their status should be checked separately.

Limitations

Based on the abstract, the overall survival analysis in this report was interim and showed only a trend in favour of pertuzumab. Other limitations are not given in the abstract and should be checked in the full text of the paper.

Original article (DOI)PubMed ClinicalTrials.gov

This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.