BMAs for Various Diagnosis
In the absence of reliable evidence, it is the opinion of the workgroup that BMAs should be considered in patients with metastatic carcinoma or multiple myeloma with bone lesions at risk for fracture regardless of tumor histology.

Rationale

There is a single low-quality study by Abdel-Rahman (2018) that assessed tumor histology as a prognostic feature of skeletal related event outcomes in patients with advanced cancer and bone metastases treated with either denosumab or zoledronic acid in a clinical trial.  The aforementioned study found that patients with non-small cell lung cancer had a shorter time to first skeletal related event than patients with other cancers. Despite the lack of evidence-based recommendations for this topic, clinicians should consider the use of BMAs regardless of tumor histology in patients with metastatic carcinoma or multiple myeloma with bone lesions at risk for fracture.

Although not meeting criteria for inclusion in analysis for this question in particular, there is evidence that specific BMAs may be favored by histology type. In multiple myeloma, zoledronic acid has been found to be superior to clodronate (Morgan 2011,2013) for skeletal related events, progression free survival (PFS) and overall survival (OS), whereas denosumab is non-inferior to zoledronic acid (Raje 2018) for skeletal related events and OS, but associated with a longer PFS. In patients with breast cancer, denosumab is shown to be superior to zoledronic acid in relation to reduced rates of skeletal related events, prolonged time to first skeletal related event and improved quality of life measures (Martin 2012, Stopeck 2010). In patients with prostate cancer, denosumab prolonged time to first skeletal related event compared to zoledronic acid (Fizazi, 2011). In a sub-study analysis, denosumab compared to zoledronic acid was associated with improved OS in patients with non-small cell lung cancer and bone metastases (Scagliotti, 2012)

Benefits/Harms of Implementation

The benefits of decreased fracture rates, avoiding surgical intervention and associated pain, reduction in other skeletal related events and improved survival (in some patients according to histologic type) weighed against the harms of osteonecrosis of the jaw and hypocalcemia, favor the use of BMAs in these populations. It is important for clinicians to be aware that renal insufficiency is observed more commonly for zoledronic compared to denosumab, whereas hypocalcemia is more frequently observed with denosumab.


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