Rebecca M. Prince

Bone Modifier Use as Adjuvant Therapy for Early Breast Cancer

Purpose of ReviewMany studies have examined the effects of adjuvant bisphosphonates on long-term breast cancer outcomes. However, results have been inconsistent. Here, we review the evidence for their role in early breast cancer.Recent FindingsIn a recent meta-analysis, no significant decreases in recurrence or breast cancer mortality were observed in the overall population. In postmenopausal women, statistically significant, but modest, reductions in distant recurrence were observed, driven by decreased bone recurrence. This translated to decreased breast cancer mortality. While most individual studies were not performed exclusively in postmenopausal patients and were not adequately powered to detect subgroup effects based on menopausal status, observed effects were highly consistent.SummaryAdjuvant bisphosphonates in postmenopausal women should be considered in individual cases of high-risk patients, where the absolute benefit justifies associated risks. There is no evidence supporting their routine use in premenopausal women except in selected patients receiving ovarian function suppression.

Hospitalisations and emergency department visits in cancer patients receiving systemic therapy: Systematic review and meta-analysis

Emergency department visits and hospitalisations (ED+H) during systemic therapy are undesirable for both patients and the health system. We undertook a systematic literature review and meta-analysis to evaluate the frequency of unplanned all-cause and treatment-related ED+H among adults receiving adjuvant or palliative-intent systemic therapy for all cancers. Randomised controlled trials (RCT) and observational studies (OS) reporting ED+H were identified from Medline and EMBASE from inception to June 2016. Quality was assessed using modified STROBE, CONSORT or PRISMA guidelines, depending on study type. A total of 112 OS (308,662 patients) and 26 RCTs (16,081 patients) met inclusion criteria. Most articles focused on palliative treatment (59%) delivered as first-line, in breast, lung and colorectal cancers. Only 20 articles reported ED frequency. Treatment-related and all-cause hospitalisations were more common in routine practice than in RCTs (29% vs. 16% and 42% vs. 28% respectively); frequency varied by treatment intent and tumour site. Methodological issues were common, particularly poor definition of the at-risk period. Hospitalisations are common, especially in unselected populations, but few articles report this and do so poorly. Routine, standardised reporting of ED+H during chemotherapy should be included in RCT reports and evaluated in routine care following adoption of new treatments.

Multi-agent chemotherapy in advanced soft tissue sarcoma (STS) – A systematic review and meta-analysis

BACKGROUND Despite a lack of improvement in overall survival (OS) with doxorubicin-based combinations over doxorubicin alone in advanced STS, the role of multi-agent chemotherapy remains poorly defined. METHODS We conducted a systematic review and meta-analysis to evaluate benefits and harms of multi-agent chemotherapy in advanced STS. Eligible studies were randomized trials of chemotherapy in advanced STS comparing single agent to multi-agent therapy. Data from studies reporting a hazard ratio (HR) and 95% confidence intervals (CI) for OS and progression-free survival (PFS) were pooled in a meta-analysis. Meta-regression was utilized to explore the association between efficacy (OS and PFS) and both toxicity and dose intensity. RESULTS We identified 22 trials published between 1974 and April 2016 and comprising 5044 patients. Overall, multi-agent chemotherapy was associated with improved OS (HR:0.79, p = 0.02), and borderline improvement in PFS (HR:0.86, p = 0.05). While the effect on OS was similar in trials with non-anthracycline controls compared to those with anthracycline controls (HR for OS 0.73 vs. 0.82, p for difference = 0.63) there was a non-significantly greater effect for multi-agent chemotherapy on PFS in non-anthracycline RCT (HR for PFS 0.73 vs. 0.91, p for difference = 0.13). Compared to studies with cytotoxic therapy-based multi-agent therapy, a non-significantly greater magnitude of effect among studies with biological/cytostatic experimental groups was seen (HR for OS 0.64 vs. 0.86, p for difference = 0.37). There was a borderline significant association between dose reductions (which were more common in combination arms) and worse PFS (beta = 0.70, p = 0.053). CONCLUSION Multi-agent chemotherapy is associated with a modest, but statistically significant improvement in outcomes in STS. Combining chemotherapy with non-cytotoxic agents might represent a promising strategy.