Efficacy and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early HER2-positive breast cancer (NeoSphere): a randomised multicentre, open-label, phase 2 trial
- Study type
- Clinical trial
- Study name
- NeoSphere
- Phase
- Phase 2
- Design
- Multicentre, open-label (unblinded) randomised trial with four groups (1:1:1:1 randomisation), with central randomisation stratified by operable, locally advanced and inflammatory breast cancer and by hormone receptor expression
- Sample size
- 417 eligible patients
- Source
- The Lancet Oncology · 2012
- Trial registration
- NCT00545688
In plain words
In this study, women with HER2-positive breast cancer were given different combinations of the targeted drugs pertuzumab and trastuzumab before surgery, with or without the chemotherapy drug docetaxel. Adding pertuzumab to trastuzumab and docetaxel meant that in more patients (45.8% vs 29.0%) the tumour had disappeared completely when the tissue was examined under the microscope after surgery, with no notable difference in how well the treatment was tolerated. The two targeted drugs together without chemotherapy also cleared the tumour in some patients and caused fewer side effects.
Key results
Treatment arms and regimens
Four neoadjuvant cycles: trastuzumab (loading dose 8 mg/kg, then 6 mg/kg every 3 weeks) plus docetaxel (75 mg/m², escalated to 100 mg/m² every 3 weeks if tolerated). Number of patients: 107.
Four neoadjuvant cycles: pertuzumab (loading dose 840 mg, then 420 mg every 3 weeks) and trastuzumab plus docetaxel. Number of patients: 107. (Trastuzumab and docetaxel doses as stated for group A.)
Four neoadjuvant cycles: pertuzumab and trastuzumab without chemotherapy. Number of patients: 107.
Four neoadjuvant cycles: pertuzumab plus docetaxel. Number of patients: 96.
Source of the regimen details: Abstract of the paper
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
Women with previously untreated (treatment-naive) HER2-positive breast cancer, including operable, locally advanced and inflammatory breast cancer.
Endpoints
Primary endpoint (in the intention-to-treat population): pathological complete response in the breast. Patients and investigators were not blinded to treatment.
Safety and side effects
The most common grade 3 or higher adverse events were neutropenia (group A: 61 of 107; group B: 48 of 107; group C: 1 of 108; group D: 52 of 94), febrile neutropenia (8, 9, zero and 7, respectively) and leucopenia (13, 5, zero and 7, respectively). The number of serious adverse events was similar in groups A, B and D (15 to 20 serious adverse events per group, in 10 to 17% of patients) but lower in group C (4 serious adverse events in 4% of patients).
Clinical significance and place in guidelines
According to the abstract, adding pertuzumab to trastuzumab and docetaxel in the neoadjuvant setting significantly increased the pathological complete response rate; the authors considered further evaluation in adjuvant trials justified and supported the neoadjuvant approach to speed up drug evaluation. This was a phase 2 study and its endpoint was pathological complete response. The status of approvals and clinical guideline recommendations should be checked separately.
Limitations
The study was phase 2 and open-label (patients and investigators were not blinded). The primary endpoint was pathological complete response in the breast and survival results are not reported in the abstract. Formal comparative analyses between the other groups are also not reported in the abstract.
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.