De-escalation of bone-modifying agents in patients with bone metastases from breast cancer: a systematic review and meta-analysis

Awan, Arif; Hutton, Brian; Hilton, John; Mazzarello, Sasha; Poznak, Catherine Van; Vandermeer, Lisa; Bota, Brianne; Stober, Carol; Sienkiewicz, Marta; Fergusson, Dean; Shorr, Risa; Clemons, Mark

doi:10.1007/s10549-019-05265-1

Cited by 25 publications

(19 citation statements)

References 31 publications

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“…The reasons for these gaps were not recorded but we suspect that this observed deviation from recommendations may have been due to a wider range of reasons, including clinical events occurring between the administrations (e.g., planned surgery or hospitalization), patients missing an appointment or difficulty attending the clinic (hospital setting), patientphysician decision or patient choice, access issues, a perception that osteoprotection is not an important aspect of cancer treatment, delays in dental treatment, or a lack of physician BTA experience. The impact of suboptimal implementation of denosumab on clinical outcomes is not clear; contradictory results have been reported in the few studies that examined the effect on SREs when de-escalating denosumab dosing to every 12 weeks compared with the recommended every 4 weeks [27][28][29][30][31][32][33]. The pharmacokinetics of denosumab support regular and consistent dosing; denosumab has a half-life of 28 days [34], and ESMO guidelines state that "unlike bisphosphates, denosumab is not stored in bone and interrupting its administration is probably not without risk.…”

Section: Discussionmentioning

confidence: 99%

Medication adherence with denosumab in patients with bone metastases from solid tumors treated in routine clinical settings: a retrospective study

Diel

Greil

Janssen

et al. 2022

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Purpose To describe (non)adherence with denosumab among patients with solid tumors and bone metastases. Methods This retrospective, observational study pooled data from two completed prospective, multicenter cohort studies (X-TREME; Study 240) in adult patients with bone metastases from primary breast, prostate, lung, kidney, or other solid cancer types and administered denosumab 120 mg in routine clinical practice in Germany and Central and Eastern Europe. The studies were conducted between May 2012 and May 2017; pooled analysis was completed in August 2021. Medication adherence was described according to a three-component consensus taxonomy: initiation (first-ever administration ≤ 90 days from bone metastasis diagnosis), implementation (actual vs prescribed dosing; optimal implementation = regular/consistent dosing), and persistence (≤ 60-day gap between administrations at 3, 6, 9, and 12 months). Descriptive analyses were conducted for each cancer type. Results The analysis included 1748 patients with solid tumors and bone metastases. Adherence with denosumab was generally high across the initiation, implementation, and persistence phases. Most patients experienced timely initiation (from 64.4% [kidney cancer] to 81.2% [breast cancer]) and optimal implementation (from 62.4% [lung cancer] to 72.5% [breast cancer]). The proportion of patients who were persistent with treatment at 6 months ranged from 41.4% (lung cancer) to 77.8% (prostate cancer). Conclusions This study revealed variations by cancer type in the initiation, implementation, and persistence of denosumab in patients with solid tumors and bone metastases in routine clinical practice. Further cancer-specific studies are warranted to examine the determinants of (non)adherence with denosumab, and potential ways to improve medication adherence.

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Section: Discussionmentioning

confidence: 99%

Medication adherence with denosumab in patients with bone metastases from solid tumors treated in routine clinical settings: a retrospective study

Diel

Greil

Janssen

et al. 2022

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“…Less-frequent dosing of btas in breast and prostate cancer is supported by data from three randomized controlled studies. In a meta-analysis, sre rates in patients with mbca were similar for zoledronate given every 12 weeks or every 3-4 weeks, regardless of whether patients started on standard dosing (every 3-4 weeks) or de-escalated dosing (every 12 weeks) 43 . A more recent trial evaluating the noninferiority of 12-weekly compared with 4-weekly dosing for btas in patients with breast cancer and crpc showed that a dose-de-escalated schedule can also be applied to pamidronate 44 .…”

Section: Choice Of Agent and Dosing Schedulementioning

confidence: 97%

Practical Update for the Use of Bone-Targeted Agents in Patients with Bone Metastases from Metastatic Breast Cancer or Castration-Resistant Prostate Cancer

et al. 2020

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Bone metastases are a significant source of morbidity and mortality for patients with breast and prostate cancer. In this review, we discuss key practical themes regarding the use of bone-targeted agents (btas) such as bisphosphonates and denosumab for managing bony metastatic disease. The btas both delay the onset and reduce the incidence of skeletal-related events (sres), defined as any or all of a need for radiation therapy or surgery to bone, pathologic fracture, spinal cord compression, or hypercalcemia of malignancy. They have more modest benefits for pain and other quality-of-life measures. Regardless of the benefits of btas, it should always be remembered that the palliative management of metastatic bone disease is multimodal and multidisciplinary. The collaboration of all disciplines is essential for optimal patient care. Special consideration is given to these key questions: What are btas, and what is their efficacy? What are their common toxicities? When should they be initiated? How do we choose the appropriate bta? What is the appropriate dose, schedule, and duration of btas?

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“…Eine Ver-längerung des Applikationsintervalles von Zoledronsäure wird auch durch Untersuchungen beim ossär metastasierten Mammakarzinom gestützt. In einer Metanalyse waren die SRE-Raten für Zoledronsäure 12-wöchentlich versus 4-wöchentlich beim ossär metastasierten Mammakarzinom ähnlich [26].…”

Section: Sonderfall Osteoprotektion Beim Adt-induzierten Knochenschwund (Ctibl)unclassified

Osteoprotektion als Baustein der Therapie des metastasierten Prostatakarzinoms: Behandlungsrealität in Deutschland und Entscheidungspfade zur Therapieoptimierung

et al. 2021

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Zusammenfassung Hintergrund Die Osteoprotektion bei Prostatakarzinompatienten spielt nicht nur in der ossär metastasierten kastrationsresistenten (mCRPC) Situation eine Rolle. Auch im ossär metastasiertem hormonsensitiven Stadium (mHSPC) und im Allgemeinen begleitend zur Androgendeprivationstherapie (ADT) wird eine Osteoprotektion empfohlen. Diese Studie soll die Anwendungsrealität der verschiedenen Arten der Osteoprotektion beim metastasierten Prostatakarzinom in Deutschland aufzeigen. Material und Methoden Es wurde ein Online-Fragebogen bestehend aus 16 Fragen zur Erfassung der Behandlungsrealität in Deutschland entwickelt und an Mitglieder der Arbeitskreise Onkologie und urologische Onkologie (AKO/AUO) sowie an Kollegen der Klinik für Urologie des Universitätsklinikums Schleswig-Holstein (Campus Lübeck), des Klinikums Braunschweig und der Technischen Universität München verschickt. Mithilfe der aktuellen Studienlage, Fachinformationen und Leitlinien wurden ferner Entscheidungspfade für das ossär metastasierte Prostatakarzinom und für den ADT-induzierten Knochenschwund entwickelt. Ergebnisse Zusammenfassend ergab die Auswertung, dass die Osteoprotektion beim ossär mCRPC zur Routine gehört. Beim ossär mHSPC hingegen wird eine Osteoprotektion seltener indiziert und ist zur Reduktion eines ADT-induzierten Knochenschwundes noch weniger im Einsatz. Denosumab wird häufiger genutzt als Zoledronsäure. Die vorgestellten Entscheidungspfade illustrieren die verschiedenen Dosierungs- und Applikationsschemata in den verschiedenen Stadien des metastasierten Prostatakarzinoms. Schlussfolgerung Die Osteoprotektion beim Prostatakarzinom ist facettenreich und nicht nur auf das ossär mCRPC beschränkt. Osteoprotektive Maßnahmen sind ein wichtiger Baustein im ganzheitlichen Therapiekonzept des metastasierten Prostatakarzinoms.

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De-escalation of bone-modifying agents in patients with bone metastases from breast cancer: a systematic review and meta-analysis

Cited by 25 publications

References 31 publications

Medication adherence with denosumab in patients with bone metastases from solid tumors treated in routine clinical settings: a retrospective study

Medication adherence with denosumab in patients with bone metastases from solid tumors treated in routine clinical settings: a retrospective study

Practical Update for the Use of Bone-Targeted Agents in Patients with Bone Metastases from Metastatic Breast Cancer or Castration-Resistant Prostate Cancer

Osteoprotektion als Baustein der Therapie des metastasierten Prostatakarzinoms: Behandlungsrealität in Deutschland und Entscheidungspfade zur Therapieoptimierung

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