La salute dell osso nelle pazienti in trattamento adiuvante. Airoldi Mario - S.C. Oncologia Medica 2 Città della Salute e della Scienza di Torino

Transcription

1 La salute dell osso nelle pazienti in trattamento adiuvante Airoldi Mario - S.C. Oncologia Medica 2 Città della Salute e della Scienza di Torino

2

3

4 BONE STRENGTH OSTEOPOROSIS SKELETAL DISORDER COMPROMISING BS LEADING TO INCREASED RISK OF FRACTURE BS HAS TWO COMPONENTS: MICROARCHITECTURE (QUALITY), BONE DENSITY (QUANTITY) BMD DXA (<2.5 T SCORE=OSTEOPOROSIS)

5

6

7

8

9 FRAX ALGORITHM understimates AI effect

10 -1.3% and -2.9% - AXELSEN

11

12

13

14

15

16

17

18

19

20 Outcomes Extended Duration AI beyond 5 yrs N (% N+) MA-17R 1918 (53%) B (42%) IDEAL 1824 (74%) DATA 1912 (67%) SOLE 4884 (99%) ABCSG (31%) Duratio n ET/AI cont DFS Benefit OS Benefit Y* N Y N N Y N N Y N N N N N? N N N New BC Benefit

21 AEs Extended Duration AI beyond 5 yrs Arthalgia AI/Plc Hot Flashes AI/Plc Vaginal Dryness AI/Plc Cardio vascular AI/Plc Fractures AI/Plc MA-17R B IDEAL DATA SOLE ABCSG

22

23

24

25

26 ABCSG-18: study design Enrolled N = 3425* Key inclusion criteria Postmenopausal women Histologically confirmed non-metastatic ER+ and/or PR+ adenocarcinoma of the breast Receiving or due to receive adjuvant non-steroidal AI therapy ECOG performance score: 0 or 1 Gnant M, et al. Lancet 2015;386: (and supplementary appendix). R A N D O M I S A T I O N Denosumab 60 mg SC Q6M n = 1711 Daily supplementation with calcium (500 mg) and vitamin D ( 400 IU) were recommended throughout study treatment Placebo SC Q6M n = 1709 Key exclusion criteria AI therapy for > 24 months before trial inclusion Previous or concurrent treatment with SERMs Evidence of metastatic disease Ongoing or previous IV BPs; oral BPs Previous denosumab therapy Known history of: Paget s disease, Cushing s disease, hyperprolactinaemia, hypercalcaemia, hypocalcaemia or other active metabolic bone disease Major surgery or traumatic injury < 4 weeks before randomisation *5 patients withdrew consent to use their data; Defined as having undergone a bilateral oophorectomy, 60 years of age, or < 60 years of age but with follicle-stimulating hormone and oestradiol levels in the postmenopausal range; Oral BP treatment if taken for 3 years or longer continuously or if taken for between 3 months and 3 years unless the patient had a washout period of at least 1 year before randomisation, or any use during the 3 months before randomisation. IV, intravenous; ECOG, Eastern Cooperative Oncology Group; ER, oestrogen receptor; Q6M, every 6 months; PR, progesterone receptor; SC, subcutaneous; SERM, selective oestrogen receptor modulator.

27 ABCSG-18: outcomes Primary endpoint Time to first clinical fracture* Secondary endpoints Percentage change in total lumbar spine, total hip and femoral neck BMD from baseline to Month 36 Incidence of new vertebral fractures at Month 36 Incidence of new or worsening of pre-existing vertebral fractures at Month 36 Disease-free survival (DFS) Bone metastasis-free survival (BMFS) Overall survival (OS) Exploratory endpoints were: the percentage change in total lumbar spine, total hip and femoral neck BMD from baseline to Months 12 and 24 (at preselected sites); the percentage change in total lumbar spine, total hip and femoral neck BMD from baseline to Months 12, 24 and 36 (at all participating clinical sites); new and new or worsening vertebral fractures at Months 12 and 24 Safety endpoints were: incidence of treatment-emergent adverse events (TEAEs); clinically significant changes in laboratory values; anti-denosumab antibody formation Gnant M, et al. Lancet 2015;386: *Defined as clinically evident fractures with associated symptoms, except for those of the skull, face, fingers, and toes, which are typically not associated with osteoporosis; Morphometric fractures identified from study radiographs and clinical vertebral fractures confirmed by radiographs.

28 Adjusted mean change in BMD (%) ABCSG-18: denosumab significantly increased BMD in the lumbar spine, total hip and femoral neck vs placebo Lumbar spine Total hip Femoral neck Placebo Denosumab (n = 986) (n = 725) (n = 475) (n = 992) (n = 717) (n = 468) (n = 995) (n = 723) (n = 469) Months since randomisation P < at all bone sites and time points 5.75% difference at Month 12* 8.28% difference at Month 24* 10.02% difference at Month % difference at Month 12* 5.85% difference at Month 24* 7.92% difference at Month % difference at Month 12* 5.19% difference at Month 24* 6.51% difference at Month 36 Gnant M, et al. Lancet 2015;386: *Note: these data represent an exploratory endpoint of the study; Note: these data represent a secondary endpoint of the study. Error bars are 95% CIs.

29 Do not copy or distribute.

30 Risk of fracture (%) Risk of fracture (%) ABCSG-18: denosumab significantly reduced the incidence of clinical fractures vs placebo regardless of baseline BMD Normal BMD (baseline T-score 1.0) Low BMD (baseline T-score < 1.0) HR = 0.44 (95% CI: ) P < Overall cumulative incidence of first clinical fractures Denosumab: n = 43/938 Placebo: n = 92/934 Placebo Denosumab HR = 0.57 (95% CI: ) P = Overall cumulative incidence of first clinical fractures Denosumab: n = 49/773 Placebo: n = 84/ Number at risk Placebo Denosumab Months since randomisation Number at risk Placebo Denosumab Months since randomisation Gnant M, et al. Lancet 2015;386: (and supplementary appendix). Percentage risk of fracture based on Kaplan Meier time-to-event analysis within each treatment group at 6-month intervals. The HR and P value were calculated from a Cox model including treatment groups as the independent variable and stratified by the randomisation stratification factors.

31

32

33

34

35

36