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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care

3672 - Incidence of hypocalcemia in a non-inferiority Phase III trial assessing prevention of symptomatic skeletal events (SSE) with Denosumab (DN) administered every 4 weeks (q4w) versus every 12 weeks (q12w): SAKK 96/12 (REDUSE)

Date

22 Oct 2018

Session

Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care

Topics

End-of-life Care

Tumour Site

Presenters

Roger von Moos

Citation

Annals of Oncology (2018) 29 (suppl_8): viii603-viii640. 10.1093/annonc/mdy300

Authors

R. von Moos1, H. Hawle2, S. Hayoz3, R. Cathomas4, A. Müller5, S. Schmid6, O. Pagani7, T. Wehrhahn8, D. Rauch9, S. Anchisi10, T. Hermanns11, M. Fehr12, S. Stoll13, P. Bützberger14, M. Zweifel15, U. Huber16, A.C. Fuhrer17, C. Schär17, S. Gillessen18, A.J. Templeton19

Author affiliations

  • 1 Department Of Oncology/hematology, Kantonsspital Graubünden, 8000 - Chur/CH
  • 2 Medical Advisor, Swiss Group for Clinical Cancer Research (SAKK), 3008 - Bern/CH
  • 3 Statistics, Swiss Group for Clinical Cancer Research (SAKK), 3008 - Bern/CH
  • 4 Oncology/hematology, Kantonsspital Graubünden, 7000 - Chur/CH
  • 5 Department Of Medical Oncology, Kantonsspital Winterthur, Winterthur/CH
  • 6 Oncology And Haematology, Kantonsspital St. Gallen, 9007 - St. Gallen/CH
  • 7 Breast Unit, IOSI - Ospedale Regionale Bellinzona e Valli, 6500 - Bellinzona/CH
  • 8 Oncology / Hematology, Kantonsspital Aarau, 5001 - Aarau/CH
  • 9 Oncology And Hematology, Spital STS AG Thun, Thun/CH
  • 10 Cancerology/oncology, Hôpital Régional Sion-Hérens-Conthey, Site de Champsec Centre du Cancer Lausanne, 1951 - Sion/CH
  • 11 Department Of Urology, University Hospital Zürich, Zürich/CH
  • 12 Gynäkologie & Geburtshilfe, Kantonsspital Frauenfeld, 8500 - Frauenfeld/CH
  • 13 Medical Oncology And Hematology, Stadtspital Triemli, 8063 - Zürich/CH
  • 14 Oncology / Hematology, Kantonsspital Baden, Baden/CH
  • 15 Oncology, Spitalzentrum Biel, Biel/CH
  • 16 Swiss Tumor Institute, Klinik Im Park Oncology Center, 8038 - Zurich/CH
  • 17 Clinical Trial Management, Swiss Group for Clinical Cancer Research (SAKK), 3008 - Bern/CH
  • 18 Department Of Oncology/hematology  , Kantonsspital St. Gallen, 9007 - St. Gallen/CH
  • 19 Medical Oncology, St. Claraspital AG, 4058 - Basel/CH
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Resources

Abstract 3672

Background

DN has shown superiority in delaying skeletal related events when given q4w over zoledronic (ZA) acid given q4w. Newer data have shown that ZA given q12w is non-inferior to ZA q4w. The primary endpoint of REDUSE is to show non-inferiority for DN q12w versus q4w (SSE). Here we present the data for the secondary endpoint hypocalcemia (HC).

Methods

Patients with metastatic breast cancer (BC) or metastatic castration resistant prostate cancer (PC) (planned N = 1380) were randomized 1:1 to receive DN q4w (Arm A) versus q12w (Arm B) after a 3-month induction phase with application q4w. All patients received vitamin D 400 U (ViD) and calcium (Ca) 500 mg daily. Measurement of serum-calcium was mandatory before each DN injection. This safety interim analysis was performed after 3.5 years of accrual. (N = 634; BC N = 351, PC N = 283).

Results

Patients who received at least 1 dose of DN were considered evaluable. HC was the most common side effect with 23.7% overall (BC 18.6%, PC 30.2%). While HC occurred in 31.6% in Arm A, the rate was 15.8% in Arm B. Grade 3/4 HC was rare (overall: 1.3%, all with PC). After 1 year of treatment, the incidence of HC was lower in both arms (A: 27.2%, B: 14.3%). Since HC improved in more patients in Arm B than Arm A whereas it got worse in Arm A compared to Arm B, a remarkable difference for HC was noticed between the two arms (Table).Table: 1703P

Change in HC grade after week 16 in patients with HC during induction treatment (196/634) (week 1 – 12: DN q4w Arm A+B, thereafter q4w Arm A, q12w Arm B)Arm A (N = 106)Arm B (N = 90)
n (%)n (%)
Worsening48 (45.3%)23 (25.6%)
Stable29 (27.4%)15 (16.7%)
Improving29 (27.4%)52 (57.8%)

Arm A: Denosumab q4w, Arm B: Denosumab q12w.

Conclusions

In our trial up to 30% of all patients treated with DN experienced HC in the q4w induction phase despite mandatory supplementation and measurement of ViD and Ca. This rate was considerably higher than reported in the registration trials of DN (PC 13.0%, BC 5.5%). After randomization the appearance of HC is remarkably lower in the q12w arm compared to q4w. This suggests that DN given q12w has a more favorable long time toxicity profile (HC) compared to DN q4w.

Clinical trial identification

NCT02051218.

Legal entity responsible for the study

Swiss Group for Clinical Cancer Research (SAKK).

Funding

Swiss State Secretariat for Education, Research and Innovation (SERI) and Santésuisse.

Editorial Acknowledgement

Disclosure

R. von Moos: Advisory board: Amgen, Novartis, Roche. S. Gillessen: Compensated consultancy and advisory roles (including IDMC): AAA International, Active Biotech, Astellas Pharma, Bayer, Bristol-Myers Squibb, CellSearch (Menarini Silicon Biosystems), Clovis, Curevac, Dendreon, Ferring, Innocrin, Janssen, MaxiVAX SA, Millennium, Novartis, Orion, Pfizer, Roche, Sanofi Aventis; Speakers Bureaus (compensated): Janssen, Novartis; Patent application for a biomarker method (WO 2009138392 A1). All other authors have declared no conflicts of interest.

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