De-escalated administration of bone-targeted agents in patients with breast and prostate cancer—A survey of Canadian oncologists

Abstract

ObjectiveQuestions remain regarding the optimal use of bone-targeted agents in patients with metastatic bone disease. The purpose of this study was to assess current clinical practice regarding the use and administration of bone-targeted agents by Canadian oncologists in patients with metastatic breast and prostate cancer.MethodsA survey was designed to explore; bone-targeted agent use in metastatic bone disease, variability in the choice and the frequency of administration of these agents. Opinions were sought on potential outcomes for future trials.ResultsA total of 193 clinicians were contacted and 90 completed our survey (response rate 49% after adjustment for inactivity). Survey respondents were medical oncologists (71.1%), radiation oncologists (21.1%) and urologists (7.8%). The findings suggest that once bone-targeted agents are started they are rarely discontinued. More agents are used in breast cancer than in prostate cancer. There was considerable interest in performing studies of de-escalated therapy in both breast and prostate cancer. Physicians requested (86%) that the primary study endpoint be the occurrence of skeletal related events and not biomarker driven.ConclusionsDespite clinical practice guidelines and widespread use, significant areas of clinical equipoise with respect to use of bone-targeted agents exist. Findings from this survey suggest that physicians are interested in de-escalated therapy for both breast and prostate patients. However, the use of multiple agents in breast cancer and the desire for skeletal related events to be the primary endpoint means that very large randomized studies will be required.

Publishing Clinical Research: Ten Pearls for Oncology Trainees and Junior Oncologists

“…For example, our group has an interest in de-escalation of bone-targeted therapies for patients with metastatic bone disease. We staggered our work into short-term projects (commentaries 9 , editorials, pilot chart review 10 , review articles), medium-term projects (surveys of patients and physicians to demonstrate clinical equipoise 11 , systematic reviews 12 ), and longer-term projects (creation of pilot singlearm and randomized feasibility data studies 13,14 ). Deadlines are thus spread out and the payoffs are layered-all hopefully one day leading to funding for a larger phase iii trial.…”

Bone-Targeted Agents for the Management of Breast Cancer Patients with Bone Metastases

“…Key questions for both physicians [93] and patients [94] that are currently under investigation include questions on optimal timing and dosing of bone-modifying therapy and what to do with this therapy upon documented disease progression.…”

Cost-effectiveness in managing skeletal related events in breast cancer: a strategy of less-intense dosing schedule of bone modifying agents

“…Additionally, the 4 mg ZA dose resulted in fewer side effects which indicate that higher doses of ZA are typically not well tolerated. It is important to note that the trials which evaluated the once-monthly 4 mg ZA were of one to 2-year duration, but it is known that cancer patients who are started on BMAs are on such agents for longer time periods (especially with the increased life expectancy of cancer patients in the modern era) (3,4). This once-monthly administration of BMAs lead to worrisome side- effects including: osteonecrosis of the jaw (ONJ), atypical femoral fractures, nephrotoxicity, hypocalcemia and other rare side effects (5).…”

“…Health care cost-benefit analysis provides data to assist physicians in determining the optimal treatment strategies for cancer patients. The patient and physician surveys show that both the patients and oncologists are willing and looking forward for de-escalating dosing regimens (4,11). This extended inter-dose time interval of 3 months is a potential solution to the substantially increasing costs of cancer treatment in appropriately selected subset of patients, and this 3-monthly dosing regimen has the potential to expand affordability in patients.…”