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COI
Dr Aapro is a consultant for
Amgen, BMS, Celgene, GSK, Helsinn, JnJ Novartis, Merck, Merck Serono, Pfizer, Pierre Fabre, Roche,
Sandoz, Tesaro,Teva, Vifor
and has received honoraria for lectures at symposia of
Amgen, Bayer Schering, Cephalon, DRL, GSK, Helsinn, Hospira, Ipsen, JnJ OrthoBiotech, Merck,
Merck Serono, Novartis, Pfizer, Pierre Fabre, Roche, Sandoz, Sanofi, Taiho, Tesaro, Teva, Vifor
No responsibility accepted forinvoluntary errors or omissions. The list may be incomplete, and does not reflect consultancy for NGOs, Universities, Governmental agencies, and others
SUPPORTIVE CARE ISSUES
in the not so young
Matti S. Aapro
IMO
Genolier
Switzerland
Friday June 30
13:30-15:30 Supportive care
• 13:30-14:00 Supportive care issues
• Matti Aapro (CH)
• 14:00:14:30 Prediction and possible reduction of toxicity of chemotherapy in older patients
• Martine Extermann (US)
• 14:30-15:00 Prehabilitation and rehabilitation
• Kwok Leung Cheung (GB) and Giuseppe Colloca (IT)
• 15:00-15:30 Cancer and no cancer pain in the elderly
• Giuseppe Colloca (IT)
4
WHOM TO THANK?
Laura Biganzoli
Robert Coleman
Diana Crivellari
Arti Hurria
Juan Morote
Hans Wildiers
And many others
SIESTA MENU
• Supportive care makes an impact
• A favourite topic: bone health
• To conclude
SIESTA MENU
• Supportive care makes an impact
• A favourite topic: bone health
• To conclude
SIOG ADVANCED COURSE 2017
Supportive care issues
A key factor for success
yet this is your only time for this topic
Temel et al NEJM 2010
Zimmermann et al Lancet 2014
Bakitas et al. Early Versus Delayed Initiation of Concurrent
Palliative Oncology Care: Patient Outcomes in the ENABLE
III Randomized Controlled Trial. J Clin Oncol. 2015
9
« Early palliative care »
Survie Globale
Temel J et al. NEJM 2010
� Standard Care
� Early Palliative Care
NOT YET READY: ESMO POSITION PAPEREven the title may change
BREAKFAST MENU
• Supportive care makes an impact
• A favourite topic: bone health
• To conclude
Results (4)
Median follow-up = 18,95 months
(range: 0 – 39,7)
OS
G8(Soubeyran et al. 2008)
• Has food intake declined over the past 3 months
due to loss of appetite, digestive problems,
chewing or swallowing difficulties?
• Weight loss during the last 3 months
• Mobility
• Neuropsychological problems
• Body Mass Index (weight in kg/height in m2)
• Takes more than 3 medications per day
• In comparison with other people of the same age,
how does the patient consider his/her health
status?
• Age
General health status Geriatric screening
Kenis, …, Wildiers, J Clin Oncol, 2013
ESMO - Recommended Algorithm for managing
Bone Health during Breast Cancer Treatment
Coleman R. and Hadji P. et al. Ann Oncol 2014;00:1–14.
Patient with cancer receiving chronic
endocrine treatment known to accelerate bone loss
Any 2 of the following RF:• Age >65 years• T-score < -1.5• Smoking (current or
history)• BMI < 20• Family history of hip
fracture • Personal history of
fragility fracture >50 years
• Oral glucocorticoid use for > 6 months
Strategy No. Mean follow-up
Absolute decrease in recurrence
Absolute decrease in BC mortality
Upfront
ATAC
BIG 1-98
9.856 5.8 yrs At 5 yrs
2.9% (SE=0.7%) 2P<.00001
1.1% (SE=0.5%) 2P=.1
Sequential
ARNO
ABCSG-8
IES
ITA
9.015 3.9 yrs At 3 yrs from treatment divergence
3.1% (SE=0.6%) 2P<.00001
0.7% (SE=0.3%) 2P=.02
16
7 trials; 30.023 patients
Limitations:
• Literature rather than individual patient data meta-analysis
• Reports of trials with different durations of follow-up
• Information on the potentially confounding baseline host factors (eg, obesity,
hypertension, diabetes, and family history of events of interest) or the use of
concurrent medications was not reported
= � �� �
17
Management of advanced prostate cancer: Specific considerations for senior adults
• First-line ADT monotherapy is the standard of care
Maximum androgen blockade
results in a small advantage in
OS, which is not clinically
relevant
Maximum androgen blockade
has significant effects on QoL
OS: Overall survival QoL: Quality of life. Prostate Cancer Trialists Collaborative Group, Lancet 2000;355:1491–1498
• Bone loss with increasedrisk of fracture1,2
LESS is BETTER ...
• Baseline bone density
• Prevent risk of osteoporosis
Androgen deprivation therapy: Side effects
• Increased risk of diabetes3
• Increased risk of fatal cardiac events4–6
Years
0
10
20
30
40
50
Cu
mu
lati
ve
fra
ctu
re
inci
de
nce
(%
)
0 1 2 3 4 5 6 7 8 9
Orchiectomy
No orchiectomy
Caution in patients with:
• History of stroke
• Chronic heart failure
• Myocardial infarction
1. Daniell et al. J Urol 1997;157:439–444. 2. Shahinian VB et al.
N Engl J Med 2005;352:154–164. 3. Keating NL et al. JCO 2006;27:4448–4456.
4. D‘Amico et al. JCO 2007;25:2420–2425. 5. Hayes et al. BJU Int 2010;106:979–85.
6. Nguyen et al. Int J Radiat Oncol Biol Phys 2011 [Epub ahead of print]
Osteoporosis in Elderly Patients
� Bone density decreases with age
� AI treatment and ADT are associated with an increased
risk of osteoporosis. Tamoxifen is somewhat “protective”
� Treatment induced bone loss can be managed with
additional medication such as vitamin D and calcium
supplements and bisphosphonates/denosumab
� AI induced decrease in bone density reverses after
treatment termination
D Crivellari et al. Crit Rev Oncol Hematol 2010;73(1):92-8
P Hadji et al. Ann Oncol 2008;19:1407-1416
RE Coleman et al. Breast Cancer Res Treat. 2010
Click to edit Master title style
Click to edit Master subtitle
style
1. Higano CS. Nat Clin Pract Urol. 2008; 5:24-34;
2. Eastell R, et al. J Bone Miner Res 2006; 21:1215-23;
3. Maillefert JF, et al. J Urol 1999; 161:1219-22;
4. Gnant MF, et al. Lancet Oncol 2008; 9:840-9;
5. Shapiro CL, et al. J Clin Oncol 2001; 19:3306-11.
CTIBL is more rapid than naturally occurring
bone loss
Click to edit Master title style
� Click to edit Master text styles
– Second level
• Third level
– Fourth level
1. Higano CS. Nat Clin Pract Urol 2008;5:24-4; 2. Eastell R, et al. J Bone Miner Res 2006;21:1215-23;
3. Maillefert JF, et al. J Urol 1999;161:1219-22; 4. Gnant MF, et al. Lancet Oncol 2008;9:840-9;
5. Shapiro CL, et al. J Clin Oncol 2001;19:3306-11
Bone loss induced by ADT for prostate cancer is
rapid and clinically significant
0.51.0
2.02.6
4.6
7.47.7
0
2
4
6
8
10
Bo
ne
lo
ss
at
1 y
ea
r (%
)
Naturally occurring
bone loss
CTIBL
24
Regulatory approval for anti-resorptive agents in cancer patients
Indication Regulatory approval
Prevention of skeletal-related events
Zoledronic acid 4 mg i.v. every 3–4 weeksDenosumab 120 mg s.c. every 4 weeksPamidronate 90 mg i.v. every 3–4 weeksClodronate 1600 mg p.o. daily Ibandronate 50 mg p.o. dailyIbandronate 6 mg i.v. monthly
All solid tumours and multiple myelomaAll solid tumoursBreast cancer and multiple myelomaOsteolytic lesions*Breast cancer* Breast cancer*
Prevention of breast cancer metastases
Zoledronic acid 4 mg i.v. 6 monthlyZoledronic acid 4 mg i.v. monthly x 6, then 3–6 monthly Clodronate 1600 mg daily
NoneNoneNone
Prevention of prostate cancer metastases
Denosumab 120 mg s.c. monthly None
Prevention of treatment-induced bone loss
Denosumab 60 mg s.c. 6 monthly Zoledronic acid 4 mg i.v. 6 monthlyAlendronate 70 mg p.o. weekly Risedronate 35 mg p.o. weekly Ibandronate 150 mg p.o. monthlyPamidronate 90 mg i.v. every 3 months
Prostate and breast cancerNoneNoneNoneNoneNone
*European approval only (not US)
i.v. – intravenous; s.c. subcutaneous; p.o. per oral
Coleman R et al. Ann Oncol 2014;00:1–14.
25
Treatment recommendations
• Bisphosphonates and denosumab prevent bone loss associated with ovarian suppression/aromatase inhibitors in early breast cancer and androgen deprivation therapy in prostate cancer
Prevention of
treatment-induced
bone loss
Coleman R et al. Ann Oncol 2014;00:1–14.
ESMO - Recommended Algorithm for managing
Bone Health during Breast Cancer Treatment
Coleman R. and Hadji P. et al. Ann Oncol 2014;00:1–14.
Patient with cancer receiving chronic
endocrine treatment known to accelerate bone loss
T-score > -2.0 and no additional
risk factorsT-score < -2.0
Exercise Calcium and vitamin D
Monitor risk and BMD at 1–2 year intervals
Any 2 of the following RF:• Age >65 years• T-score < -1.5• Smoking (current or
history)• BMI < 20• Family history of hip
fracture • Personal history of
fragility fracture >50 years
• Oral glucocorticoid use for > 6 months
Exercise Calcium and vitamin D
Bisphosphonate therapy (zoledronic acid, alendronate, risedronate, ibandronate) and
Denosumab*
Monitor BMD every 2 years Check compliance with oral therapy
*in view of ABCSG-18 data
Bone Recurrence Breast Cancer Mortality
Adjuvant bisphosphonates reduce the rate of bone
metastasis and improve breast cancer survival in
post-menopausal patients
EBCTCG Lancet 2105
Adjuvant AIs reduce the rate relapse and improve
breast cancer survival in
post-menopausal patients compared to tamoxifen
EBCTCG Lancet 2105
EBCTCG 2005-06 Overview Peto SABCS 2007
10
0 5 10 0 5 10 0 5 10
50
0
40
30
20
Anthra
31.0%
Taxane
25.9%
%
+ SE
15.3
12.8
YearsYearsYears
CMF
31.3%
Anthra
27.0%
Control
36.4%
CMF
32.2%
20.5
17.8
19.9
16.5
Taxanes > Anthra > CMF > No Chemo
Taxanes improve BC mortality
Preliminary results from 11 trials
4.2%
4.3% 5.1%
M.J. Piccart-Gebhart at EBCC 08
When to start Bone Targeted Therapy
� It takes some months before the benefit is evident as bone lesions need time to heal
� Thus guidelines indicate: start immediately
after diagnosis of bone metastases
� BUT use clinical judgment: if the patient’s life
expectancy is very short, it might not be useful
Aapro et al Annals of Oncology 2008
Denosumab efficacy results across pivotal
studies in patients with bone metastases*
*All data come from the primary analysis phase of these studies
1Stopeck AT, Lipton A, Body JJ, et al. J Clin Oncol 2010;28:5132-5139.2Fizazi K, Carducci M, Smith M, et al. Lancet 2011;377:813-822.3Henry DH, Costa L, Goldwasser F, et al. J Clin Oncol 2011;29:1125-1132.
Study Month
0.0
0.2
0.4
0.6
0.8
1.0
24 30
Breast Cancer (n=2046)1
Other Solid Tumors orMultiple Myeloma (n=1776)3Prostate Cancer (n=1901)2
HR 0.82 (95% CI: 0.71, 0.95)
P<0.001 (Non-inferiority)
P = 0.01 (Superiority)
HR 0.82 (95% CI: 0.71, 0.95)
P=0.0002 (Non-inferiority)
P=0.008 (Superiority)
HR 0.84 (95% CI: : 0.71, 0.98 )
P=0.0007 (Non-inferiority)
P=0.06 (Superiority)
12 180 6
Study Month
24 3012 180 6
Study Month
24 3012 180 6
Pro
po
rtio
n o
f su
bje
cts
with
ou
t S
RE
Adverse events in the presence of denosumab
or zoledronic acid: ONJ and others
Patient incidence, n (%) Zoledronic Acid (n=2836) Denosumab (n=2841)
Adverse events (AEs) 2745 (96.8) 2734 (96.2)
Most common AEs
Nausea 895 (31.6) 876 (30.8)
Anaemia 859 (30.3) 771 (27.1)
Fatigue 766 (27.0) 769 (27.1)
Back pain 747 (26.3) 718 (25.3)
Decreased appetite 694 (24.5) 656 (23.1)
CTCAE Grade 3, 4 or 5 AEs 2009 (70.8) 2000 (70.4)
Serious AEs 1620 (57.1) 1599 (56.3)
AEs leading to study discontinuation 280 (9.9) 270 (9.5)
Infectious AEs 1218 (42.9) 1233 (43.4)
Infectious serious AEs 309 (10.9) 329 (11.6)
Acute phase reactions (first 3 days) 572 (20.2) 246 (8.7)
Renal AEs* 335 (11.8) 262 (9.2)
Cumulative rate of ONJ 37 (1.3) 52 (1.8)
Year 1 15 (0.5) 22 (0.8)
Year 2 28 (1.0) 51 (1.8)
Hypocalcemia 141 (5.0) 273 (9.6)
New primary malignancy 18 (0.6) 28 (1.0)
*Includes increased blood creatinine, renal failure, acute renal failure, proteinuria, renal impairment, oliguria, increased blood urea,
hypercreatininemia, decreased urine output, anuria, decreased creatinine renal clearance, azotemia, chronic renal failure, abnormal renal
function test and abnormal blood creatinine. ONJ; osteonecrosis of the jaw.
Lipton A, Siena S, Rader M, et al. ESMO 2010: abstract 1249P and poster presentation.
WHAT DOSE OF BPs TO USE in M1 BrCA
PLEASE NOTICE THAT RECENT STUDIES
INDICATE THAT MONTHLY ZOLEDRONIC ACID
MAY NOT BE NEEDED FOR LONG-TERM
CONTROL OF SREs
HOWEVER EXPERT CONSENSUS SUGGESTS
MONTHLY FOR 3-6 MONTHS before 3 monthly
Amadori Lancet 2014; Hortobagyi ASCO 2014; Himelstein ASCO 2015
Himelstein ASCO 2015
SIESTA MENU
• Supportive care makes an impact
• A favourite topic: bone health
• To conclude
Late registration deadline: September 28, 2017Find out more at www.siog.org
“From research to practice: incorporating geriatric oncology into patient care”
THANK YOUto all the patients
and their physicians, nurses and carers