Cancer patients frequently experience disease- and drug-related side effects. Cancer-related pain, chemotherapy-induced nausea and vomiting (CINV), and chemotherapy-induced peripheral neuropathy (CIPN) are among the most common side effects.  Approximately one-third of cancer patients undergoing therapy and over three-fourths of those with advanced disease experience some degree of pain.1 Disease-related pain may be nociceptive (aching or throbbing) or neuropathic (tingling or burning sensation) in nature, or may present as bone pain caused by skeletal metastases.  Nociceptive pain typically results from somatic or visceral injury, while neuropathic pain is primarily due to tumor infiltration of the nerves or postherpetic neuralgia.  Importantly, in addition to malignancy-related neuropathy, neuropathic pain may also be associated with cancer therapy (eg, postsurgical neuropathy, postradiation plexopathy, CIPN)2 with CIPN affecting an estimated 30% to 40% of patients receiving chemotherapy.3

Cancer-Related Bone Pain

Up to two-thirds of patients with breast and prostate cancer develop bone metastases, with bone pain affecting over 60% of all cancer patients. Importantly, data indicate that bone pain is associated with increased rates of anxiety, depression and mortality, and may negatively impact performance status and quality of life. Currently utilized treatment modalities include systemic analgesics (eg, opioids, nonsteroidal anti-inflammatory drugs), bisphosphonates (eg, pamidronate, zoledronic acid), and radiopharmaceutical therapy (eg, strontium-89, rhenium-186, rhenium-188, samarium-153).4,5 Unfortunately, these treatment modalities are not universally effective and side effects may limit use in some patients.4 As such, various alternative agents have been recently approved for or currently under investigation for the alleviation of cancer-related bone pain.  

Denosumab (Xgeva, Amgen), a human monoclonal antibody that targets the RANK ligand to suppress osteoclast-induced bone resorption, has recently been approved for the prevention of skeletal-related events in patients with bone metastases from solid tumors.6 One study comparing the efficacy of single-dose denosumab with single-dose pamidronate in patients with breast cancer or multiple myeloma with bone metastases found that patients treated with denosumab experienced a more sustained decrease in bone turnover than those treated with pamidronate. This is an important finding, as bone pain often results as a complication of uncontrolled bone destruction.7  Furthermore, various Phase 3 studies comparing denosumab with zoledronic acid demonstrated that denosumab was superior to zoledronic acid in delaying/preventing skeletal-related events in patients with bone metastases, and that compared with zoledronic acid, fewer denosumab-treated patients experienced worsening of bone pain.8 Finally, in addition to improved efficacy, the use of denosumab prevents the need for intravenous bisphosphonate infusions, and may offer a valuable treatment option for patients limited by bisphosphonate-associated renal toxicity or osteonecrosis.7

Sotatercept (ACE-011, Acceleron Pharma), a chimeric protein that increases osteoblast differentiation and promotes osteogenesis, is currently being studied for the treatment of multiple myeloma (MM) patients with osteolytic lesions. A Phase 2, randomized, double-blind, placebo-controlled study of sotatercept in stage II/III MM patients receiving standard chemotherapy found that sotatercept therapy was associated with lesion improvement; importantly, 20% of sotatercept patients reported persistent pain reduction following the first dose of drug therapy, suggesting that this agent may be useful for MM patients suffering from bone pain.9