Breast cancer (metastatic)
INTRODUCTION: Median survival from metastatic breast cancer is 12 months without treatment, but young people can survive up to 20 years with the disease, whereas in other metastatic cancers this would be considered unusual. METHODS AND OUTCOMES: We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of first-line hormonal treatment? What are the effects of second-line hormonal treatment in women who have not responded to tamoxifen? What are the effects of first-line chemotherapy? What are the effects of first-line chemotherapy in combination with a monoclonal antibody? What are the effects of second-line chemotherapy? What are the effects of treatments for bone metastases? What are the effects of treatments for spinal cord metastases? What are the effects of treatments for cerebral or choroidal metastases? We searched: Medline, Embase, The Cochrane Library, and other important databases up to June 2009 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We found 77 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. CONCLUSIONS: In this systematic review we present information relating to the effectiveness and safety of the following interventions: first-line hormonal treatment using anti-oestrogens (tamoxifen), ovarian ablation, progestins, selective aromatase inhibitors, or combined gonadorelin analogues plus tamoxifen; second-line hormonal treatment using progestins or selective aromatase inhibitors; first-line non-taxane combination chemotherapy; first-line taxane-based combination chemotherapy; first-line high- versus low-dose standard chemotherapy; first-line chemotherapy plus monoclonal antibody (bevacizumab, trastuzumab); first-line chemotherapy plus tyrosine kinase inhibitor (lapatinib); second-line taxane-based combination chemotherapy; second-line capecitabine or semi-synthetic vinca alkaloids for anthracycline-resistant disease; second-line chemotherapy plus tyrosine kinase inhibitor (lapatinib); and treatment for bone, spinal, or choroidal metastases using bisphosphonates, intrathecal chemotherapy, radiotherapy (alone or plus corticosteroids) radiation sensitisers, or surgical resection.
Stebbing J and Ngan S. Breast cancer (metastatic). Clinical Evidence 2010; 09:811.
Substantive changes at this update
Selective aromatase inhibitors for first-line treatment in postmenopausal women One systematic review added.The review included the same RCTs as those previously reported in Clinical Evidence, and reached the same conclusions – that selective aromatase inhibitors and tamoxifen were equally effective at improving responses rates and were associated with similar overall survival. One subsequent RCT added suggesting that exemestane may increase response rates compared with tamoxifen, but that there was no significant difference in overall survival between groups. Categorisation unchanged (Beneficial).
Selective aromatase inhibitors as second-line treatment in postmenopausal women One systematic review added.The review included the same RCTs as those previously reported in Clinical Evidence, and came to the same conclusions – that selective aromatase inhibitors and anti-oestrogens or progestins were equally effective at improving response rates and were associated with similar overall survival. Categorisation unchanged (Beneficial).
Taxane-based combination chemotherapy for first-line treatment One systematic review added, which confirmed previous conclusions that taxane-based combinations improved response rates compared with non-taxane-based combinations but did not affect survival. Another RCT added found that weekly paclitaxel significantly increased response rates, time to progression, and survival compared with paclitaxel every 3 weeks. Categorisation unchanged (Trade off between benefits and harms).
Chemotherapy plus bevacizumab for first-line treatment New option for which we identified one open-label RCT.The RCT found that adding bevacizumab to paclitaxel increased response rates and improved progression-free survival compared with paclitaxel alone but did not increase overall survival. Categorised as Unknown effectiveness as cannot draw conclusions from a single RCT.
Chemotherapy plus tyrosine kinase inhibitor for first-line treatment in women with overexpressed HER2/neu oncogene New option for which we found one RCT. The RCT found that adding lapatinib to paclitaxel increased time to disease progression, progression-free survival, and response rates in women who were HER2 positive compared with paclitaxel alone but that the combination conferred no additional benefit if given, without testing, to women shown to be HER2 negative. Categorised as Unknown effectiveness as cannot draw conclusions from a single RCT.
Semisynthetic vinca alkaloids for second-line treatment One RCT added, which found that adding gemcitabine to semisynthetic vinca alkaloids may improve progression-free survival compared with semisynthetic vinca alkaloids alone but did not seem to improve response rates or overall survival. Categorisation of semisynthetic vinca alkaloids for second-line treatment of anthracycline-resistant disease unchanged (Unknown effectiveness).
Chemotherapy plus bevacizumab for second-line treatment New option for which we found one RCT.The RCT found that adding bevacizumab to capecitabine improved response rates and quality of life compared with capecitabine alone but did not increase survival.  Categorised as Unknown effectiveness as, despite positive results from this single RCT, more confirmatory evidence is needed to draw firm conclusions.
Chemotherapy plus tyrosine kinase inhibitor for second-line treatment New option for which we found one RCT. The RCT found that adding lapatinib to standard second-line combination chemotherapy improved response rates, time to disease progression, and survival in women whose tumours overexpress the HER2/neu oncogene and who have progressed after treatment with regimes that included an anthracycline, a taxane, and trastuzumab.  Categorised as Unknown effectiveness as, despite positive results from this single RCT, more confirmatory evidence is needed to draw firm conclusions.
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Phase III Open-Label Randomized Study of Eribulin Mesylate Versus Capecitabine in Patients With Locally Advanced or Metastatic Breast Cancer Previously Treated With an Anthracycline and a Taxane. ( 31 March 2015 )
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