Terry L Ng1,2,3, Megan M Tu4, Mohammed F K Ibrahim5, Bassam Basulaiman6, Sharon F McGee7,4,8, Amirrtha Srikanthan7,4,8, Ricardo Fernandes9, Lisa Vandermeer4, Carol Stober4, Marta Sienkiewicz4, Ahwon Jeong4, Deanna Saunders4, Arif A Awan7,4,8, Brian Hutton4,10, Mark J Clemons7,4,8. 1. Division of Medical Oncology, Department of Medicine, University of Ottawa, Ottawa, ON, K1H 8L6, Canada. teng@toh.ca. 2. Ottawa Hospital Research Institute, Ottawa, ON, Canada. teng@toh.ca. 3. Division of Medical Oncology, The Ottawa Hospital Cancer Centre, 501 Smyth Road, Ottawa, ON, K1H 8L6, Canada. teng@toh.ca. 4. Ottawa Hospital Research Institute, Ottawa, ON, Canada. 5. Division of Clinical Sciences, Medical Oncology, Northern Ontario School of Medicine, Thunder Bay, ON, P7B 5E1, Canada. 6. Comprehensive Cancer Center -Medical Oncology, King Fahad Medical City, Riyadh, Saudi Arabia. 7. Division of Medical Oncology, Department of Medicine, University of Ottawa, Ottawa, ON, K1H 8L6, Canada. 8. Division of Medical Oncology, The Ottawa Hospital Cancer Centre, 501 Smyth Road, Ottawa, ON, K1H 8L6, Canada. 9. Division of Medical Oncology, London Regional Cancer Program, London Health Sciences Centre, University of Western Ontario, London, ON, Canada. 10. School of Epidemiology and Public Health, University of Ottawa, Ottawa, ON, Canada.
Abstract
PURPOSE: Bone-modifying agents (BMAs) for bone metastases are commonly prescribed for many years even though randomized clinical trials are only 1-2 years in duration. A systematic review on the risk-benefit of BMA use for > 2 years in breast cancer or castrate-resistant prostate cancer was conducted. METHODS: MEDLINE, Embase, and Cochrane databases were searched (1970-February 2019) for randomized and observational studies, and case series reporting on BMA efficacy (skeletal-related events and quality of life) and toxicity (osteonecrosis of the jaw, renal impairment, hypocalcemia, and atypical femoral fractures) beyond 2 years. RESULTS: Of 2107 citations, 64 studies were identified. Three prospective and 9 retrospective studies were eligible. Data beyond 2 years was limited to subgroup analyses in all studies. Only one study (n = 181) reported skeletal-related event rates based on bisphosphonate exposure, with decreased rates from 27.6% (0-24 months) to 15.5% (> 24 months). None reported on quality of life. All 12 studies (denosumab (n = 948), zoledronate (n = 1036), pamidronate (n = 163), pamidronate-zoledronate (n = 522), ibandronate (n = 118)) reported ≥ 1 toxicity outcome. Seven bisphosphonate studies (n = 1077) and one denosumab study (n = 948) reported on osteonecrosis of the jaw. Across three studies (n = 1236), osteonecrosis of the jaw incidence ranged from 1 to 4% in the first 2 years to 3.8-18% after 2 years. Clinically significant hypocalcemia ranged from 1 to 2%. Severe renal function decline was ≤ 3%. Atypical femoral fractures were rare. CONCLUSIONS: Evidence informing the use of BMA beyond 2 years is heterogeneous and based on retrospective analysis. Prospective randomized studies with greater emphasis on quality of life are needed. PROSPERO REGISTRATION NUMBER: CRD42019126813.
PURPOSE: Bone-modifying agents (BMAs) for bone metastases are commonly prescribed for many years even though randomized clinical trials are only 1-2 years in duration. A systematic review on the risk-benefit of BMA use for > 2 years in breast cancer or castrate-resistant prostate cancer was conducted. METHODS: MEDLINE, Embase, and Cochrane databases were searched (1970-February 2019) for randomized and observational studies, and case series reporting on BMA efficacy (skeletal-related events and quality of life) and toxicity (osteonecrosis of the jaw, renal impairment, hypocalcemia, and atypical femoral fractures) beyond 2 years. RESULTS: Of 2107 citations, 64 studies were identified. Three prospective and 9 retrospective studies were eligible. Data beyond 2 years was limited to subgroup analyses in all studies. Only one study (n = 181) reported skeletal-related event rates based on bisphosphonate exposure, with decreased rates from 27.6% (0-24 months) to 15.5% (> 24 months). None reported on quality of life. All 12 studies (denosumab (n = 948), zoledronate (n = 1036), pamidronate (n = 163), pamidronate-zoledronate (n = 522), ibandronate (n = 118)) reported ≥ 1 toxicity outcome. Seven bisphosphonate studies (n = 1077) and one denosumab study (n = 948) reported on osteonecrosis of the jaw. Across three studies (n = 1236), osteonecrosis of the jaw incidence ranged from 1 to 4% in the first 2 years to 3.8-18% after 2 years. Clinically significant hypocalcemia ranged from 1 to 2%. Severe renal function decline was ≤ 3%. Atypical femoral fractures were rare. CONCLUSIONS: Evidence informing the use of BMA beyond 2 years is heterogeneous and based on retrospective analysis. Prospective randomized studies with greater emphasis on quality of life are needed. PROSPERO REGISTRATION NUMBER: CRD42019126813.
Entities:
Keywords:
Bisphosphonates; Bone metastases; Denosumab; Skeletal-related events; Systematic review
Authors: Mashari AlZahrani; Mark Clemons; Lisa Vandermeer; Marta Sienkiewicz; Arif Ali Awan; Brian Hutton; Gregory R Pond; Terry L Ng Journal: J Bone Oncol Date: 2020-11-10 Impact factor: 4.072
Authors: Mashari Alzahrani; Mark Clemons; Marta Sienkiewicz; Noa Shani Shrem; Sharon F McGee; Lisa Vandermeer; Sandeep Sehdev; Marie France Savard; Arif Awan; Christina Canil; Brian Hutton; Gregory Pond; Deanna Saunders; Terry Ng Journal: Support Care Cancer Date: 2021-05-22 Impact factor: 3.603
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Authors: Megan M Tu; Mark Clemons; Carol Stober; Ahwon Jeong; Lisa Vandermeer; Mihaela Mates; Phillip Blanchette; Anil Abraham Joy; Olexiy Aseyev; Gregory Pond; Dean Fergusson; Terry L Ng; Kednapa Thavorn Journal: Curr Oncol Date: 2021-05-13 Impact factor: 3.677
Authors: J E Brown; S L Wood; C Confavreux; M Abe; K Weilbaecher; P Hadji; R W Johnson; J A Rhoades; C M Edwards; P I Croucher; P Juarez; S El Badri; G Ariaspinilla; S D'Oronzo; T A Guise; C Van Poznak Journal: J Bone Oncol Date: 2021-06-11 Impact factor: 4.072