Background Adjuvant trastuzumab significantly improves outcomes for patients with HER2-positive early breast cancer. The standard treatment duration is 12 months but shorter treatment could provide similar efficacy while reducing toxicities and cost. We aimed to investigate whether 6-month adjuvant trastuzumab treatment is noninferior to the standard 12-month treatment regarding disease-free survival. Methods This study is an open-label, randomised phase 3 non-inferiority trial. Patients were recruited from 152 centres in the UK. We randomly assigned patients with HER2-positive early breast cancer, aged 18 years or older, and with a clear indication for chemotherapy, by a computerised minimisation process (1:1), to receive either 6-month or 12-month trastuzumab delivered every 3 weeks intravenously (loading dose of 8 mg/kg followed by maintenance doses of 6 mg/kg) or subcutaneously (600 mg), given in combination with chemotherapy (concurrently or sequentially). The primary endpoint was disease-free survival, analysed by intention to treat, with a non-inferiority margin of 3% for 4-year disease-free survival. Safety was analysed in all patients who received trastuzumab. This trial is registered with EudraCT (number 2006-007018-39), ISRCTN (number 52968807), and ClinicalTrials.gov (number NCT00712140).

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.

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Background Postmastectomy radiotherapy in patients with four or more positive axillary nodes reduces breast cancer mortality, but its role in patients with one to three involved nodes is controversial. We assessed the effects of postmastectomy radiotherapy on quality of life (QOL) in women with intermediate-risk breast cancer. MethodsSUPREMO is an open-label, international, parallel-group, randomised, controlled trial. Women aged 18 years or older with intermediate-risk breast cancer (defined as pT1-2N1; pT3N0; or pT2N0 if also grade III or with lymphovascular invasion) who had undergone mastectomy and, if node positive, axillary surgery, were randomly assigned (1:1) to receive chest wall radiotherapy (50 Gy in 25 fractions or a radiobiologically equivalent dose of 45 Gy in 20 fractions or 40 Gy in 15 fractions) or no radiotherapy. Randomisation was done with permuted blocks of varying block length, and stratified by centre, without masking of patients or investigators. The primary endpoint is 10-year overall survival. Here, we present 2-year results of QOL (a prespecified secondary endpoint). The QOL substudy, open to all UK patients, consists of questionnaires (European Organisation for Research and Treatment of Cancer QLQ-C30 and QLQ-BR23, Body Image Scale, Hospital Anxiety and Depression Scale [HADS], and EQ-5D-3L) completed before randomisation, and at 1, 2, 5, and 10 years. The prespecified primary outcomes within this QOL substudy were global QOL, fatigue, physical function, chest wall symptoms, shoulder and arm symptoms, body image, and anxiety and depression. Data were analysed by intention to treat, using repeated mixed-effects methods. This trial is registered with the ISRCTN registry, number ISRCTN61145589.Findings Between Aug 4, 2006, and April 29, 2013, 1688 patients were enrolled internationally and randomly assigned to receive chest wall radiotherapy (n=853) or not (n=835). 989 (79%) of 1258 patients from 111 UK centres consented to participate in the QOL substudy (487 in the radiotherapy group and 502 in the no radiotherapy group), of whom 947 (96%) returned the baseline questionnaires and were included in the analysis (radiotherapy, n=471; no radiotherapy, n=476). At up to 2 years, chest wall symptoms were worse in the radiotherapy group than in the no radiotherapy group (mean score 14·1 [SD 15·8] in the radiotherapy group vs 11·6 [14·6] in the no radiotherapy group; effect estimate 2·17, 95% CI 0·40-3·94; p=0·016); however, there was an improvement in both groups between years 1 and 2 (visit effect -1·34, 95% CI -2·36 to -0·31; p=0·010). No differences were seen between treatment groups in arm and shoulder symptoms, body image, fatigue, overall QOL, physical function, or anxiety or depression scores.Interpretation Postmastectomy radiotherapy led to more local (chest wall) symptoms up to 2 years postrandomisation compared with no radiotherapy, but the difference between groups was small. These data will inform shared decision making while we await survival (trial primary endpoint) results.

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