See Appendix for individual names.Background: Pertuzumab combined with trastuzumab and docetaxel is the standard first-line therapy for HER2-positive metastatic breast cancer, based on results from the phase III CLEOPATRA trial. PERUSE was designed to assess the safety and efficacy of investigator-selected taxane with pertuzumab and trastuzumab in this setting.
Patients and methods:In the ongoing multicentre single-arm phase IIIb PERUSE study, patients with inoperable HER2-positive advanced breast cancer (locally recurrent/metastatic) (LR/MBC) and no prior systemic therapy for LR/MBC (except endocrine therapy) received docetaxel, paclitaxel or nab-paclitaxel with trastuzumab [8 mg/kg loading dose, then 6 mg/kg every 3 weeks (q3w)] and pertuzumab (840 mg loading dose, then 420 mg q3w) until disease progression or unacceptable toxicity. The primary end point was safety. Secondary end points included overall response rate (ORR) and progression-free survival (PFS).
Results:Overall, 1436 patients received at least one treatment dose (initially docetaxel in 775 patients, paclitaxel in 589, nabpaclitaxel in 65; 7 discontinued before starting taxane). Median age was 54 years; 29% had received prior trastuzumab. Median treatment duration was 16 months for pertuzumab and trastuzumab and 4 months for taxane. Compared with docetaxel-containing therapy, paclitaxel-containing therapy was associated with more neuropathy (all-grade peripheral neuropathy 31% versus 16%) but less febrile neutropenia (1% versus 11%) and mucositis (14% versus 25%). At this preliminary analysis (52 months' median follow-up), median PFS was 20.6 [95% confidence interval (CI) 18.9-22.7] months overall (19.6, 23.0 and 18.1 months with docetaxel, paclitaxel and nab-paclitaxel, respectively). ORR was 80% (95% CI 78%-82%) overall (docetaxel 79%, paclitaxel 83%, nab-paclitaxel 77%).Conclusions: Preliminary findings from PERUSE suggest that the safety and efficacy of first-line pertuzumab, trastuzumab and taxane for HER2-positive LR/MBC are consistent with results from CLEOPATRA. Paclitaxel appears to be a valid alternative taxane backbone to docetaxel, offering similar PFS and ORR with a predictable safety profile.ClinicalTrials.gov: NCT01572038.
48 Background: Electrochemotherapy (ECT) combines the administration of poorly permeable chemotherapeutic agents with electroporation. It has been shown to be effective when compared with other treatments. This study assessed how breast cancer patients were benefited and identified potential problems at a designated treatment centre. Methods: This was a single centre prospective study of patients with cutaneous metastases from breast cancer. Patients who fulfilled NICE UK (National Institute Of Clinical Excellence) and local guidelines were treated. Gabapentin was given prior to general anaesthesia. Intravenous Bleomycin 15,000IU/m2 was given as a bolus. Treatment was commenced 8 minutes later with Cliniporator. Electrical pulses were delivered via an electrode inserted through the skin surface. Treatment response, disease progression free duration, post-operative pain and length of in-patient stay (LOS) were recorded. Patients recorded a symptom diary post treatment. Results: 20 treatments were performed in 16 patients from 2011-2015 with 53 separate areas treated. 8 patients had diffuse lesions, 5 had discrete lesions and 3 had both diffuse and discrete areas. 16 patients were being treated with ECT for the first time and 4 patients required 2 treatments. Median LOS was 3 days. Median follow up was 6 months (range 3-12).12 patients had complete response (75%) and 4 patients partial response. There was no disease progression for 6 months or more in 9 patients (56%) and 2 further patients had disease stabilised for 3 months with systemic or cutaneous progression in the remaining patients in 3 months or less. There were no deaths or immediate adverse events from ECT. 5 Patients (31%) with extensive diffuse chest wall disease reported persistent discomfort post treatment requiring extended period of post treatment analgesia. Conclusions: Electrochemotherapy is safe and effective treatment for cutaneous metastases. Appropriate patient selection for treatment, pre-emptive analgesia, post treatment support and follow up is essential in order to maximise the benefits and minimise potential side-effects particularly in extensive chest wall disease.
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