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Observational Study
. 2020 Apr;28(4):1855-1865.
doi: 10.1007/s00520-019-04988-7. Epub 2019 Jul 26.

Prospective observational study to evaluate the persistence of treatment with denosumab in patients with bone metastases from solid tumors in routine clinical practice: final analysis

Ferdinand Haslbauer  1 , Andreas Petzer  2 , Martin Safanda  3 , Antoaneta Tomova  4 , Miriam Porubska  5 , Zoltán Bajory  6 , Daniela Niepel  7 , Christine Jaeger  8 , Katja Bjorklof  9 , Dmitry Kalinin  10 , Richard Greil  11
Affiliations
Observational Study

Prospective observational study to evaluate the persistence of treatment with denosumab in patients with bone metastases from solid tumors in routine clinical practice: final analysis

Ferdinand Haslbauer et al. Support Care Cancer. 2020 Apr.

Abstract

Purpose: In the integrated analysis of phase III head-to-head trials in patients with advanced solid tumors, denosumab demonstrated superiority over zoledronic acid in preventing skeletal-related events (SREs). Regular and continued drug use (persistence) is a precondition of clinical efficacy; persistence in real-life is yet undetermined for denosumab.

Methods: This was a single-arm, prospective, observational, non-interventional study in 598 patients with bone metastases from breast, prostate, lung, or other solid tumors treated with denosumab every four weeks in real-world clinical practice in Austria, Czech Republic, Hungary, Slovakia, and Bulgaria. Persistence was defined as denosumab administration at ≤ 35-day intervals over 24 or 48 weeks, respectively.

Results: Previous SREs were found in 10.9% of patients. 62.6% were persistent over 24 weeks and 40.1% over 48 weeks. The Kaplan-Meier median (95% CI) time to non-persistence was 274.0 days (232.0, 316.0). The most frequent reason for non-persistence was delayed administration. There was a trend towards weaker analgesics over time, with approximately 60% of patients not requiring any analgesics. Serum calcium remained within the normal range throughout the study. Adjudicated osteonecrosis of the jaw was documented in three patients with an incidence per patient-year (95% CI) of 0.012 (0.004, 0.029).

Conclusions: Most patients received denosumab regularly once every four weeks over 24 weeks of treatment. Non-persistence was mainly due to delayed administration. The incidence of adverse drug reactions, especially of osteonecrosis of the jaw, was in line with expectations from previous studies.

Keywords: Bone metastases; Denosumab; Observational study; Persistence; Solid tumors.

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Conflict of interest statement

Ferdinand Haslbauer, Martin Safanda, Antoaneta Tomova, Zoltán Bajory, Miriam Porubska, and Dmitry Kalinin have no conflicts of interest to declare. Andreas Petzer declares to hold a non-remunerative position of influence as advisory board member of Amgen and has received speaker honoraria of Amgen. Richard Greil has received research grants from Celgene, Merck, Roche, Takeda, AstraZeneca, Novartis, Amgen and BMS, and consulting fees from Celgene, Roche, BMS, Takeda, Abbvie, AstraZeneca, and Novartis. Christine Jaeger, Katja Bjorklof, and Daniela Niepel are employees of Amgen and hold Amgen stock.

Figures

Fig. 1
Fig. 1
Patient disposition. [a] 634 patients were enrolled; 319 from Austria, 130 from Bulgaria, 109 from the Czech Republic, 58 from Slovakia, and 18 from Hungary. Thirty-six patients were excluded from the analysis. The reasons for exclusion from analysis were violation of inclusion or exclusion criteria, erroneous double entry in the database, or entry by mistake, e.g., erroneously entering a training data set in the real database instead of the training database. [b] Only patients who did not die and were not lost to follow-up are included in this section
Fig. 2
Fig. 2
Distribution of tumor types, overall and by country (%)
Fig. 3
Fig. 3
Persistence for denosumab at 24 weeks, overall and by tumor type (%, 95% CI)
Fig. 4
Fig. 4
Persistence for denosumab at 24 weeks, overall and by country (%, 95% CI)
Fig. 5
Fig. 5
Reasons for non-persistence for denosumab at 24 weeks, overall and by country (%) (S)ADR, (serious) adverse drug reaction; permissible time windows between injections of a maximum of 35 days were defined by the protocol
Fig. 6
Fig. 6
Proportion of patients with AQA score ≤ 2 at baseline shifting to AQA score > 2 at later denosumab doses
See this image and copyright information in PMC

References

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