International Guidelines for Management of Metastatic Breast Cancer: Combination vs Sequential Single-Agent Chemotherapy

JNCI Journal of the National Cancer Institute, Sep 2009

Compared with treatment options for early-stage breast cancer, few data exist regarding the optimal use of chemotherapy for metastatic breast cancer (MBC). The choice of using a combination of cytotoxic chemotherapies vs sequential single agents is controversial. At the 6th European Breast Cancer Conference, the European School of Oncology Metastatic Breast Cancer Task Force convened an open debate on the relative benefits of combination vs sequential therapy. Based on the available data, the Task Force recommends sequential monotherapy as the preferred choice in advanced disease, in the absence of rapid clinical progression, life-threatening visceral metastases, or the need for rapid symptom and/or disease control. Patient- and disease-related factors should be used to choose between combination and sequential single-agent chemotherapy for MBC. Additional research is needed to determine the impact of therapy on patient-rated quality of life and to identify predictive factors that can be used to guide therapy.

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International Guidelines for Management of Metastatic Breast Cancer: Combination vs Sequential Single-Agent Chemotherapy

Fatima Cardoso Philippe L. Bedard Eric P. Winer Olivia Pagani Elzbieta Senkus-Konefka Lesley J. Fallowfield Stella Kyriakides Alberto Costa Tanja Cufer Kathy S. Albain on behalf of the ESO-MBC Task Force Compared with treatment options for early-stage breast cancer, few data exist regarding the optimal use of chemotherapy for metastatic breast cancer (MBC). The choice of using a combination of cytotoxic chemotherapies vs sequential single agents is controversial. At the 6th European Breast Cancer Conference, the European School of Oncology Metastatic Breast Cancer Task Force convened an open debate on the relative benefits of combination vs sequential therapy. Based on the available data, the Task Force recommends sequential monotherapy as the preferred choice in advanced disease, in the absence of rapid clinical progression, life-threatening visceral metastases, or the need for rapid symptom and/or disease control. Patient- and diseaserelated factors should be used to choose between combination and sequential single-agent chemotherapy for MBC. Additional research is needed to determine the impact of therapy on patient-rated quality of life and to identify predictive factors that can be used to guide therapy. - Many challenges exist in the management of metastatic breast cancer (MBC). As opposed to early disease, for which level 1 evidence exists for the majority of treatment alternatives, there are few recognized therapeutic standards for MBC, particularly following initial chemotherapy (1). Randomized controlled trials in MBC are usually conducted in the first-line setting and address specific questions regarding the efficacy, safety, and tolerability of individual drugs. The design of these trials is sometimes at odds with the questions clinical oncologists face in daily practice. Several international guidelines for adjuvant therapy are widely used (24), but consensus statements regarding the management of MBC are lacking (5). Acknowledging the urgent need for these initiatives, the European School of Oncology (ESO) joined with the European Breast Cancer Conference (EBCC) to create an MBC Task Force in 2005. The task force held its first open meeting at the EBCC-5 in Nice in March 2006. This interactive session addressed many of the main issues in MBC, and 12 consensus statements regarding MBC management were subsequently published (1). At the EBCC-6 in Berlin in April 2008, the second public session on MBC Guidelines was held. During this session, three of the most controversial issues outlined in the 12 statements were selected for further discussion. Here, we summarize the discussion and the related recommendations regarding the optimal use of chemotherapy in MBC, focusing on the still unresolved issue of whether it is better to treat MBC patients sequentially with single cytoxic agents or to treat them simultaneously with a combination of drugs. The initial consensus statement regarding this subject (consensus statement 9) from the ESO-MBC Task Force guidelines reads: The choice between sequential use of single cytotoxic drugs and combination chemotherapy should be taken after consideration of the factors mentioned in [Table 1], with greatest emphasis on the need for a rapid and significant response and on quality of life (QoL). For the majority of patients, overall survival (OS) outcomes from sequential use of single cytotoxic drugs are equivalent to combination chemotherapy. Duration of each regimen and number of regimens should be tailored to each individual patient (1). Although the Early Breast Cancer Trialists Collaborative Group (EBCTCG) overview established the survival benefit of adjuvant polychemotherapy (6), the role of polychemotherapy in MBC remains largely unsettled. Unlike the adjuvant setting, in which the goal of therapy is cure, the aim of therapy in the setting of MBC is essentially palliation. Stepwise advances in chemotherapy have produced statistically significant improvements in survival (7). Nevertheless, tolerability and QoL are important factors Patient related Menopausal status Biological age and comorbidities (including organ dysfunction) Performance status and adverse effects of prior therapy Socioeconomic and psychological factors Patient preference Available therapies in the patients country in therapeutic decision making that must be balanced with any potential gains in disease response or survival. Objective improvements in OS are difficult to demonstrate in individual trials (8), leading some authors to question whether OS is an appropriate endpoint for clinical trials testing novel therapeutic approaches for metastatic disease (9). Accordingly, many recent registration trials were designed to detect improvements in progression-free interval and were not adequately powered to evaluate the impact of new treatments on OS (1012). Crossover to the novel agent following progression in the monotherapy arm was not mandated, limiting the application of these studies (...truncated)


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Fatima Cardoso, Philippe L. Bedard, Eric P. Winer, Olivia Pagani, Elzbieta Senkus-Konefka, Lesley J. Fallowfield, Stella Kyriakides, Alberto Costa, Tanja Cufer, Kathy S. Albain, on behalf of the ESO-MBC Task Force. International Guidelines for Management of Metastatic Breast Cancer: Combination vs Sequential Single-Agent Chemotherapy, JNCI Journal of the National Cancer Institute, 2009, pp. 1174-1181, 101/17, DOI: 10.1093/jnci/djp235