Long-term impact of bone-modifying agents for the treatment of bone metastases: a systematic review
A partir d’une revue de la littérature publiée entre 1970 et 2019 (12 études), cette étude analyse les effets d’une utilisation, pendant une durée supérieure à 2 ans, d’agents thérapeutiques ciblant les os pour traiter les métastases osseuses chez des patients atteints d’un cancer du sein ou de la prostate résistant à la castration
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.