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