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

Abstract

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.

Keywords: Denosumab; Implementation; Initiation; Medication adherence; Persistence; Real-world study.

Fig. 1

Forms of adherence and nonadherence with denosumab. Percentages within colored circles denote the proportion of patients by cancer type. Please refer to Table 2 and Supplementary Fig. 2 for additional data and full adherence definitions. ^aTime to initiation was defined as the time from diagnosis of bone metastasis to first-ever denosumab administration. ^bEach denosumab administration for patients with ≥ 3 doses of denosumab. Patients classified as optimal or suboptimal according to the extent to which gaps between administrations correspond to the recommended administration gap of 28 days, in terms of both regularity and consistency. ^cNo gap of > 60 days between consecutive denosumab administrations from initiation. BC breast cancer, KC kidney cancer, LC lung cancer, OC other types of cancer, PC prostate cancer

Fig. 2

Quality of life assessed at month 3 of denosumab initiation via the EQ-5D-5L questionnaire domains in patients with a breast, b prostate, c lung, d kidney, and e other cancer types. Patients may have received radiotherapy for palliative pain. a Twenty-two point seven percent and 30.3% of patients had a history of pain medication (analgesics) prior to enrollment and at 3 months after the first dose of denosumab, respectively; 81.2% initiated denosumab within 90 days of bone metastasis (BM) diagnosis, and 86.8% were persistent at 3 months. b Fifteen point nine percent and 27.4% of patients had a history of pain medication (analgesics) prior to enrollment and at 3 months after the first dose of denosumab, respectively; 70.1% initiated denosumab within 90 days of BM diagnosis, and 86.6% were persistent at 3 months. c Thirty-eight point three percent and 36.0% of patients had a history of pain medication (analgesics) prior to enrollment and at 3 months after the first dose of denosumab, respectively; 77.9% initiated denosumab within 90 days of BM diagnosis, and 70.3% were persistent at 3 months. d Thirty-three point nine percent and 40.7% of patients had a history of pain medication (analgesics) prior to enrollment and at 3 months after the first dose of denosumab, respectively; 64.4% initiated denosumab within 90 days of BM diagnosis, and 84.8% were persistent at 3 months. e Forty-three point five percent and 49.7% of patients had a history of pain medication (analgesics) prior to enrollment and at 3 months after the first dose of denosumab, respectively; 76.3% initiated denosumab within 90 days of BM diagnosis, and 71.9% were persistent at 3 months. EQ-5D-5L EuroQoL 5-Dimension 5-Level