Systematic review and indirect comparison of first line treatments for Human Epidermal Growth Factor Receptor 2 positive (HER2+) advanced or metastatic breast cancer

Trial description: Objective: To find out what is the clinical efficacy and tolerability of specified first-line treatments for advanced or metastatic breast cancer in women who are HER2+ through a systematic review on the clinical effectiveness and adverse effects of treatments in this setting from both Randomised Controlled Trials (RCTs) and non-RCTs, including indirect/mixed treatment comparisons of effects outcomes. Rationale: It forms the base of clinical comparision and economic comparison that are required by National Institute for Health and Clinical Excellence (NICE) technology appraisal submission in England and other reimbursement agencies such as Scottish Medicines Consortium (SMC), All Wales Medicines Strategy Group (AWMSG). Data Source: all RCTs and non-RCTs in MEDLINE and MEDLINE In-Process, EMBASE, Cochrane Database of Systematic Reviews (CDSR), Cochrane Central Register of Controlled Trials (CENTRAL), DARE Database of Abstracts of Reviews of Effects (DARE), Cumulative Index to Nursing and Allied Health Literature (CINAHL), Science Citation Index (SCI), Conference Proceedings Citation Index – Science (CPCI-S), ClinicalTrials.gov, Current Controlled Trials Register, WHO International Clinical Trials Registry Platform(ICTRP), US Food and Drug Administration (FDA), European Medicines Agency (EMA), American Society for Clinical Oncology (ASCO)annual meeting, European Society for Medical Oncology (ESMO) annual conference, European Cancer Organisation (ECCO) andEuropean Breast Cancer Conference (EBCC), San Antonio Breast Cancer Symposium: Home (SABCS).Study design and method: The population of interest are patients with HER2+ advanced or metastatic breast cancer who had not received prior therapy for advanced or metastatic disease. Patients may have undergone therapy or surgery for early breast cancer. Comparators of interest are: Lapatinib; Docetaxel alone; Paclitaxel alone; Capecitabine alone; Trastuzumab and docetaxel; Trastuzumab and paclitaxel; Trastuzumab and capecitabine; Trastuzumab and vinorelbine. The primary outcomes of interest for the clinical effects review were: Response rates: Overall survival (OS); Time to progression (TTP); Progression free survival (PFS); Patient reported outcomes (PRO); Adverse effects of treatment; Discontinuations due to adverse events; Health-related quality of life.Only published or unpublished RCTs/non RCTs were eligible for inclusion. Cross-over RCTs were included if data were presented at cross-over. Studies published as abstracts or conference presentations were not included. Full published papers relating to any potentially relevant abstracts were sought. Where full papers were not identified the abstracts of potentially relevant studies were noted for consideration for any future updates to this review. Any studies with English abstracts but whose full reports were in languages other than English were not extracted but were listed for information only. An information specialist selected records for further assessment on the basis of title and abstract. Obvious false positives (such as animal studies, commentaries and news items, and records on issues unrelated to the topic of interest) were removed at this stage. Full documents were obtained and assessed for relevance by two reviewers independently. The papers were evaluated for inclusion based on the pre-defined inclusion criteria for participants, interventions, comparators, outcomes and study design. Any discrepancies were resolved through discussion and/or by consulting a third reviewer. Records reporting potentially relevant trials but only as conference abstracts were noted and were reported to inform any future updates to this review. Two reviewers assessed the quality of each of the included studies and a third reviewer checked a sample of studies. The studies were appraised using the minimum criteriaspecified in NICE guidelines for the conduct of technology assessments which were adapted from Centre for Reviews and Dissemination (CRD) criteria. Two reviewers independently extracted the data from the full papers using a template/form in an Excel spreadsheet. A third reviewer compared the extraction, and checked any discrepancies. A summary of data extracted from the included trials was presented. The included studies were summarised in tables and in the text, firstly by outcome, and then by treatment.