Tag: General Medical Oncology & Hematology

Denosumab (Xgeva) was approved by the FDA for the prevention of  Skeletal Related Events (SRE’s) in patients with bone metastases from solid tumors. Denosumab is a monoclonal antibody targeting a protein called RANKL (Receptor Activator for Nuclear Factor kappa B Ligand). RANKL also known as  ODF (osteoclast differentiation factor) is an important molecule necessary for maintaining bone homeostasis. Overproduction of RANKL leads to increased osteoclastic activity resulting in bone resorption. Accelerated bone resorption can not only result in osteoporosis, but has also been implicated in the development of tumor related bone metastases. Denosumab binds to RANKL negating the formation, function and survival of osteoclasts.

Two international randomized studies demonstrated the superiority of Denosumab over Zoledronic acid in patients  with bone metastases, secondary to Breast Cancer and Castrate Resistant Prostate Cancer. In a third study involving patients with other solid tumors with bone metastases, Denosumab was found to be non-inferior to Zoledronic acid.

Denosumab, a RANK ligand inhibitor is a welcome addition to IV bisphosphonates, Pamidronate (Aredia) and Zoledronic acid (Zometa).

The role of Bevacizumab in combination with chemotherapy for patients with advanced Non Small Cell Lung Cancer is well established. However the safety of Bevacizumab in this patient population with brain metastases has been unclear with the potential risk of CNS bleed. This issue was addressed in the PASSPORT trial which enrolled nonsquamous histology Non Small Cell Lung Cancer patients with treated brain metastases. The addition of bevacizumab to conventional chemotherapy or erlotinib in this trial was associated with a low incidence of CNS bleed suggesting that bevacizumab could be safely given for patients with Non Small Cell Lung Cancer with treated brain metastases.

How do mutations and overexpression of certain oncogenes impact treatment decisions? So, Here is an answer the Oncoprescribe way.

If a patient with colon cancer has a tumor with KRAS mutation Erbitux or Vectibix ( EGFR targeted monoclonal antibodies ) will not work.

However if a patient with Non Small Cell Lung Cancer has a tumor with mutations involving exon 19 or exon 21, small molecule Tyrosine Kinase Inhibitors such as Tarceva (Erlotinib) may be more effective than chemotherapy.

Tumors in patients with Non Small Cell Lung Cancer with high ERCC 1 gene expression are resistant to platinum compounds and non-platinum combination regimens should be a serious consideration.