The safety profile of denosumab in oncology beyond the safety of denosumab as an anti-osteoporotic agent: still more to learn.

INTRODUCTION: Initially endorsed as an antiosteoporotic agent, denosumab ‒ human monoclonal antibody inhibiting the receptor activator of nuclear factor kappa-B ligand (RANKL)‒ has currently shown an anticancer potential, rationalizing its exploitation in oncology. A prerequisite for leveraging denosumab in oncology is a favorable safety profile.

AREAS COVERED: The present review provides an overview of the adverse events of denosumab in oncology, with a focus on hypocalcemia, medication-related osteonecrosis of the jaw, atypical femoral fracture(s), post-denosumab vertebral fractures, increased risk of infections, and excess of second primary cancer. Representative studies addressing the safety and efficacy of denosumab compared to bisphosphonates in oncology are summarized. Critical gaps in the literature concerning the safety of denosumab in oncology are highlighted as opposed to plenty of available safety data on denosumab as an antiosteoporotic agent.

EXPERT OPINION: Despite the generally acceptable safety profile of denosumab in oncology, many issues remain unresolved. Further research is mandatory to counteract current challenges, namely: (i) validation of risk factors for adverse events; (ii) elucidation of the pathophysiology of the adverse events in search of actionable molecular pathways; (iii) illumination of the association of denosumab with increased risk of infections and/or second primary cancer; (iv) establishment of optimal diagnostic, and therapeutic protocols.