Table 3.
Cancer and bone: Recommendations for consideration if current management guidance is disrupted during the COVID-19 pandemic (ASCO guidelines are included for breast cancer, prostate cancer and myeloma and ESMO guidelines for lung cancer and other solid tumours, though it should be emphasised that, as expected, there is a high level of commonality among guidelines. Therefore, recommended adaptations for disruption caused by the pandemic are intended to guide decisions whichever guidelines are normally used).
| GUIDANCE COMMON TO ALL SOLID TUMOUR TYPES AND MYELOMA | ||
|---|---|---|
| CURRENT GUIDANCE (ASCO, ESMO) | RECOMMENDATIONS FOR CONSIDERATION IF ADHERENCE TO GUIDANCE IS DISRUPTED DURING COVID-19 PANDEMIC | |
| Radiotherapy is one of the main therapeutic approaches to palliate pain in patients with bone metastasis. | Continue radiotherapy as needed, but consider giving as a single (not fractionated) dose. | |
| Calcium and vitamin D supplementation (eg, calcium 500 mg and vitamin D 400 IU daily) has been prescribed or strongly recommended within clinical trials of zoledronic acid or denosumab and is recommended within the package inserts of both drugs. | Continue with calcium and vitamin D supplementation. | |
| Orthopaedic surgery (high risk of fracture, metastatic long bone fracture, spinal cord compression) | These situations represent a medical emergency and surgery should not be delayed. | |
| Dental evaluation prior to start of zoledronic acid or denosumab is recommended as invasive dental procedures or ill-fitting dental appliances during therapy are a common predisposing factor in cases of ONJ. | Maintain dental evaluation if at all possible, or at least patient/physician visual inspection when dentistry appointments are not available. | |
| BREAST CANCER | ||
| INDICATION | CURRENT GUIDANCE (ASCO) | RECOMMENDATIONS FOR CONSIDERATION IF ADHERENCE TO GUIDANCE IS DISRUPTED DURING COVID-19 PANDEMIC |
| Advanced Breast Cancer, bone Metastases [24] | Patients with breast cancer who have evidence of bone metastases should be treated with a bone modifying agent. Options include
|
Patients with breast cancer who have evidence of bone metastases should be treated with a bone modifying agent. Options include
|
| Early Breast Cancer, adjuvant bisphosphonates [25] | It is recommended that, if available, zoledronic acid (4 mg intravenously every 6 months) or clodronate (1,600 mg/d orally) be considered as adjuvant therapy for postmenopausal patients with breast cancer who are deemed candidates for adjuvant systemic therapy | It is recommended that, if available, zoledronic acid (4 mg intravenously every 6 months) or clodronate (1,600 mg/d orally) be considered as adjuvant therapy for postmenopausal patients with breast cancer who are deemed candidates for adjuvant systemic therapyWhen infusion therapy is limited, consider zoledronic acid 5 mg once a year |
| Early Breast Cancer, prevention of bone loss [21] | Patients with osteoporosis or who are at increased risk of osteoporotic fractures based on clinical assessment or risk assessment tools, bone-modifying agents, such as oral bisphosphonates, intravenous (IV) bisphosphonates or subcutaneous denosumab at the osteoporosis-indicated dosage, may be offered to reduce the risk of fracture. Hormonal therapies for osteoporosis management (eg, estrogens) are generally avoided in patients with hormonal-responsive cancers Additionally, specific populations may be considered appropriate candidate for bone-modifying agents:
|
Timely access to DEXA scans to assess BMD may not be possible, but fracture risk assessment, such as the WHO FRAX score (https://www.sheffield.ac.uk/FRAX/tool.aspx) should be considered to assess those at high risk of osteoporotic fracture. Patients with osteoporosis or who are at increased risk of osteoporotic fractures, bone-modifying agents, such as oral bisphosphonates, intravenous bisphosphonates are favoured agents to avoid the potential interruption of denosumab dosing and associated rebound fracture risk. In patients presently receiving denosumab or zoledronic acid consider off site, drive-through or home administration if feasible. In patients presently on denosumab (60 mg every 6 months) consider oral bisphosphonate via telemedicine immediately in patients at high risk of fracture until they can resume original therapy. |
| PROSTATE CANCER | ||
| INDICATION | CURRENT GUIDANCE (ASCO) | RECOMMENDATIONS FOR CONSIDERATION IF ADHERENCE TO GUIDANCE IS DISRUPTED DURING COVID-19 PANDEMIC |
| Advanced Prostate Cancer – Bone Metastases [26] | In men with metastatic CRPC (mCRPC), either zoledronic acid (minimally symptomatic or asymptomatic disease) or denosumab (disease independent of symptoms) (both at bone metastasis-indicated dosages: zoledronic acid, 4 mg iv, 3–4 weekly; denosumab, 120 mg sc, 4 weekly) is recommended for preventing or delaying skeletal-related events (SREs). | Patients with prostate cancer who have evidence of bone metastases should be treated with a bone modifying agent. Options include • denosumab, 120 mg subcutaneously
|
| In men with symptomatic mCRPC, Ra-223 is recommended to extend overall survival. In men with symptomatic mCRPC and bone pain, radium-223 (Ra-223) should be considered for reducing symptomatic skeletal events and improving health-related QoL. Systemic therapies for the treatment of mCRPC such as abiraterone/prednisone, enzalutamide, docetaxel and cabazitaxel have been shown to reduce SREs, improve bone pain and health-related QoL, and/or improve overall survival in mCRPC. Mitoxantrone has also been shown to improve pain and health-related QoL. The optimal sequencing or combination of these therapies with bone-targeted agents is unclear, and recommendations to patients should be done in consultation with a clinician. |
If Ra-223 not available, consider external beam or sterotactic radiotherapy for bone pain and bisphosphonates or denosumab for reducing SREs and improving health-related QoL (please see above for recommend options). Consider using oral anticancer therapies, that have demonstrated a decrease in SREs such as abiraterone or enzalutamide. |
|
| There is evidence to suggest harm in the form of increased fracture risk with the combination of Ra-223 when administered with abiraterone and prednisone initiation; that combination should be avoided. Current guidelines do not support concurrent use of Ra-223 with other secondary therapies known to prolong survival for mCRPC. | Avoid combination of Ra-223 with other therapies. | |
| Bone loss due to ADT or other treatments affecting hormone levels [26] | For men with non-metastatic prostate cancer at high risk of fracture receiving ADT, denosumab at the osteoporosis-indicated dosage should be considered to reduce the risk of fracture. In situations or jurisdictions where denosumab is contraindicated or not available, a bisphosphonate is a reasonable option. Baseline bone mineral density (BMD) testing with conventional dual x-ray absorptiometry is encouraged for men before starting ADT to help determine fracture risk and to identify those individuals who would probably benefit from pharmacological intervention. | Timely access to DEXA scans to assess BMD may not be possible, but fracture risk assessment, such as the WHO FRAX score (https://www.sheffield.ac.uk/FRAX/tool.aspx) should be considered to assess those at high risk of osteoporotic fracture. If denosumab administration is not possible, consider annual infusion of zoledronic acid at osteoporosis dose. If this is not possible, consider oral bisphosphonates at osteoporosis doses |
| MULTIPLE MYELOMA | ||
| INDICATION | CURRENT GUIDANCE(ASCO) | RECOMMENDATIONS FOR CONSIDERATION IF ADHERENCE TO GUIDANCE IS DISRUPTED DURING COVID-19 PANDEMIC |
| MGUS, asymptomatic myeloma (SMM) [27] | Watchful waiting for standard risk SMM. Clinical trial may be considered for high risk SMM. |
Watchful waiting. Scheduled visits of patients with stable disease can be delayed with safety. Alternatively, blood examination in local laboratories and consultation via telemedicine is encouraged. |
| Symptomatic myeloma [27] | Intravenous administration of pamidronate 90 mg or zoledronic acid 4 mg every 3 to 4 weeks, or denosumab 120 mg every 4 weeks If patients have problems of renal impairment, denosumab is preferred compared to iv aminobisphosphonates Treatment with the bone-modifying agents is recommended to continue for up to 2 years Continuous use of the agents depends on discretion of physicians |
|
| Relapsed and/or refractory myeloma [27] | Treatment of biochemically relapsed should be individualized. All clinically relapsed patients with symptoms due to myeloma should be treated immediately. | Watchful waiting may be considered for patients with biochemical relapses, especially for patients with a slow and gradual increase in the paraprotein level. New onset of end-organ damage features (CRAB) and a history of aggressive relapse with rapid deterioration of the clinical presentation should receive next-line treatment without delay. Regarding the selection of treatment regimen, orally administered agents (ixazomib, lenalidomide, pomalidomide, and panobinostat) should be considered. |
| LUNG and OTHER SOLID TUMOUR SITES (except breast and prostate cancer) | ||
| INDICATION | CURRENT GUIDANCE (ESMO) | RECOMMENDATIONS FOR CONSIDERATION IF ADHERENCE TO GUIDANCE IS DISRUPTED DURING COVID PANDEMIC |
| Advanced cancer, bone metastases [28] | Bone targeted agents:
|
Bone targeted agents:
• denosumab, 120 mg subcutaneously
|