management of advanced prostate cancer in senior … · advanced prostate cancer in senior adults:...

July 2014 version

Management of

advanced prostate

cancer in senior adults:

a booming area

Matti Aapro

Multidisciplinary Oncology Institute

Genolier, Switzerland

• Invited speaker / advisory boards

• Sanofi

• Amgen

• GlaxoSmithKline

• Hoffmann-Laroche

• Ferring

• Ipsen

• Janssen

• Novartis

• Pfizer

• Sandoz

3

Disclosures

Treatment options for advanced Prostate Ca

in senior adults

• Castration-sensitive metastatic prostate cancer (mCSPC):

• hot from ASCO and Lancet. NOT AN APPROVED INDICATION….

• Castration-resistant metastatic prostate cancer (mCRPC)

• Palliative therapy for bone metastases

• SIOG guidelines

4

E3805 (CHAARTED) - Chemo-Hormonal vs Androgen

Ablation Randomized Trial in Extensive Disease

N = 780

ADT + Docetaxel (75mg/m2)

for 6 cycles without prednisone

R

A

N

D

O

M

I

Z

E

Stratify:

Extent of metsHigh vs Low

Age≥70 vs <70

ECOG PS0-1 vs 2

CAB >30 daysYes vs No

Prior adjuvant hormonal Tt

> 12 vs ≤12 mo

SRE preventionYes vs No

• Follow-up to

time to

progression

and OS

• Chemotherapy

at investigator’s

discretion at

progression

ADT alone

• ADT allowed up to 120 days prior to

randomization

• Intermittent ADT dosing not allowed

Sweeney C et al. ASCO 2014 – LBA2

ADT: Androgen Deprivation Therapy; OS: overall survival; CAB: ;complete androgen blockade SRE:

skeletal related events; PS: performance status



• ADT allowed up to 120 days prior to

randomization

• Intermittent ADT dosing not allowed


ADT: Androgen Deprivation Therapy; D: docetaxel (75mg/m2 without prednisone for 6 cycles)




ADT: Androgen Deprivation Therapy; D: docetaxel (75mg/m2 without prednisone for 6 cycles)

GETUG-15

Presented By Michael Morris at 2014 ASCO Annual Meeting

NO PATIENT ABOVE AGE 68….study from 2004 to 2008

Comparison to GETUG15

Presented By Michael Morris at 2014 ASCO Annual Meeting

Treatment options for advanced Prostate Ca

in senior adults

• Castration-sensitive metastatic prostate cancer (mCSPC)



• SIOG guidelines

11

Androgen deprivation therapy in advanced PCa:

Specific considerations for senior adults

• Maximum androgen blockade

results in a small advantage in

OS, which is not clinically

relevant

• Maximum androgen blockade

increases side effects and has

significant effects on QoL

Prostate Cancer Trialists Collaborative Group. Lancet 2000;355:1491–8

ADT: Androgen Deprivation Therapy; OS: overall survival; QoL: quality of life12

First-line ADT in monotherapy is the standard of care

Androgen deprivation therapy: adverse events

• Bone loss with increased risk of

fracture1,2

• Increased risk of diabetes3

• Increased risk of fatal cardiac

events4–6

1. Daniell et al. J Urol 1997;157:439–44

2. Shahinian VB et al. N Engl J Med 2005;352:154–64

3. Keating NL et al. J Clin Oncol 2006;27:4448–56

4. D‘Amico et al. J Clin Oncol 2007;25:2420–25

5. Hayes et al. BJU Int 2010;106:979–85

6. Nguyen et al. Int J Radiat Oncol Biol Phys 2012;82:1411-

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

LESS IS BETTER!

Caution in patients with:

� History of stroke

� Chronic heart failure

� Myocardial infarction

� Baseline bone density

� Prevent risk of osteoporosis

Management of advanced PCa:

Specific considerations for senior adults (2/4)



� Docetaxel

� 3-weekly schedule is the standard of care1*

� Weekly or bi-weekly schedule for frail patients?2-3

� Cabazitaxel

� Abiraterone acetate

� Enzalutamide

� Sipuleucel-T


• SIOG guidelines

14

1. Berthold D et al. J Clin Oncol 2008;26:242-5

2. Droz JP et al. BJU Int 2010;106:462-9

3. Kellokumpu-Lehtinen P et al. Lancet Oncol 2013;14:117–124

Docetaxel: age does not affect survival (TAX 327)

0.2 0.4 0.6 0.8 1 1.2 1.4

ITT

Age < 65 years

Age ≥ 65 years

Age ≥ 75 years

Pain: no

Pain: yes

KPS ≥ 80

KPS ≤ 70

Hazard ratio in favour of

Docetaxel+P Mitoxantrone+P

15Tannock IF et al. N Engl J Med 2004;351:1502-12; Horgan et al. J. Geriatr Oncol 2014; 5: 119-126

P: prednisone

• Among men ≥75 years, 3-weekly Docetaxel+P resulted in more dose reductions than weekly schedule (22% versus 8%, p = 0.007) but tolerability was otherwise comparable.

• Both Docetaxel schedules were associated with more favorable efficacy than mitoxantrone

Phase 2 study of weekly docetaxel + prednisolone

vs prednisolone alone in mCRPC

Docetaxel weekly+ Prednisolone

Prednisolone

PFS (median)[95% CI]

11 months[5.8–16.2]

4 months[2.4–5.6]

OS (median) [95% CI]

27 months[19.8–34.2]

18 months[15.2–20.8]

Survival rate (%)– 1-year– 2-year

82%61%

67%29%

12-week PSA response rate

69% 36%

QoL improvement– Physical function– Pain– Fatigue– Nausea/vomiting– Global QoL

27%52%38%17%27%

3%16%29%8%

16%

Toxic outcomes N

Gastrointestinal: grade ≥2

Nausea

Vomiting

Diarrhoea

4

1

5

Other/Constitutional: grade ≥2

Nail changes

Alopecia

Conjunctivitis/tearing

Fatigue/Anorexia

Peripheral neuropathy

Atrial flutter

Fluid retention

27

9

8

6

5

4

4

• Median age 70 years

• No cross-over

16

Fossa SD et al. Eur Urol 2007;52:1691–9

mCRPC: metastatic castrate-resistant prostate cancer; OS: overall survival; PFS: progression-free survival;

QoL: quality of life

Phase 3 study of bi-weekly versus 3-weekly

docetaxel plus prednisone in mCRPC

Docetaxelbi-weekly + P

(n=170)

Docetaxel3-weekly + P

(n=169)p

TTTF (median)

[95% CI]

5.6 mo

[5.0–6.2]

4.9 mo

[4.5–5.4]0.014

OS (median)

[95% CI]

19.5 mo

[15.9–23.1]

17 mo

[15.0–19.1]0.021

PSA response 49% 42% 0.49

Best clinical response- CR or PR

- Stable

- Progression

23%

46%

8%

22%

46%

11%

0.95

17

Kellokumpu-Lehtinen P et al. Lancet Oncol 2013;14:117–124

mCRPC: metastatic castrate-resistant prostate cancer; TTTF: Time to Treatment Failure: OS: overall survival

ALP: Alkaline phosphatase

Docetaxelbi-weekly + P

(n=170)

Docetaxel3-weekly + P

(n=169)

Hematological

- Neutropenia

- Leucopenia

- Anemia

- Thrombocytopenia

- Febrile neutropenia

36%

13%

1%

1%

4%

53%

29%

1%

0

14%

Non-hematological

- Fatigue

- Infection without

neutropenia

- Neutropenic

infection

- �ALP

- Diarrhea

- Nausea

15%

11%

6%

9%

1%

1%

15%

12%

24%

6%

2%

1%

Efficacy Grade ≥ 3 toxicities

MATuRITY: Prospective registry in men aged

70+ with mCRPC

At 6 monthsTaxane†

(N=140)

Non-taxane‡

(N=193)P

OS rate 91% 81% 0.027

PFS 66% 50% <0.001

Best clinical benefit 60% 36% <0.001

PSA ↘ ≥ 50% 52.5% 37.4% 0.018

Docetaxel

Grade ≥3 toxicity%

Fatigue 17.1%

Nausea/vomiting 14%

Neutropenia

Febrile neutropenia

9.8%

2.6%

Sensory neuropathy 9.3%

Diarrhea 8.8%

Anemia 7.8%

Loss of appetite 7.3%

Nail change 6.7%

Droz JP et al. ESMO 2012;Poster 934P 18

†75mg/m2 q3w in 83.9% of cases

‡Hormonal manipulations or non-taxane chemotherapy

Bahl A Annals of Oncol 2013; 24: 2402-2408P: prednisone 19

100

90

80

70

60

50

40

30

20

10

00 6 12 18 30

Mitoxantrone+P

% s

urv

ivin

g

Time (months)

Cabazitaxel+P

HR 0.72

(95% CI: 0.61-0.84)

P<0.0001

24

Cabazitaxel significantly improves survival vs

mitoxantrone (TROPIC, post-docetaxel)

755 patients with mCRPC who progressed during or after docetaxel

N HR (95% CI)

All randomized patients 755 0.70 (0.59–0.83)

ECOG status: 0,1 694 0.68 (0.57–0.82)

ECOG status: 2 61 0.81 (0.48–1.38)

Measurable disease: no 350 0.72 (0.55–0.93)

Measurable disease: yes 405 0.68 (0.54–0.85)

Number of previous chemotherapies: 1 528 0.67 (0.55–0.83)

Number of previous chemotherapies: ≥2 227 0.75 (0.55–1.02)

Age<65 years 295 0.81 (0.61–1.08)

Age≥65 years 460 0.62 (0.50–0.78)

Pain at baseline: no 314 0.57 (0.43–0.77)

Pain at baseline: yes 310 0.76 (0.59–0.98)

Rising PSA at baseline: no 159 0.88 (0.61–1.26)

Rising PSA at baseline: yes 583 0.65 (0.53–0.80)

Progression during docetaxel treatment 219 0.65 (0.47–0.90)

Progression <3 months after docetaxel 339 0.70 (0.55–0.91)

Progression ≥3 months after docetaxel 192 0.75 (0.51–1.11)

Cabazitaxel (TROPIC):

Survival not influenced by age

Favors CABA+P Favors MITO+P

20

de Bono et al. Lancet 2010;376:1147–54

ECOG: Eastern Cooperative Oncology Group; CABA+P: cabazitaxel+prednisone;

MITO+P: mitoxantrone+prednisone

Cabazitaxel (European compassionate use

program) - Safety in senior adults

<70 years(n=238)

70-74 years(n=100)

75+ years(n=88)

Treatment exposure

- N cycles, median (range)

- Dose delay for drug-related AE

Dose reduction for any cause

- G-CSF primary prophylaxis (C1)

4 (1-16)

4.3%

18.5%

39.2%

4 (1-12)

13.0%

16.0%

46.1%

4 (1-11)

5.7%

15.9%

50.3%

Hematological, grade ≥3

- Neutropenia

- Leucopenia

- Anemia

- Febrile neutropenia

- Neutropenic sepsis

15.0%

6.2%

5.0%

5.2%

1.0%

16.7%

8.3%

4.4%

5.6%

1.6%

23.4%

9.7%

4.1%

5.5%1.4%

Non-hematological, grade ≥3

- Fatigue

- Asthenia

- Diarrhea

- Nausea

- Vomiting

- Hematuria

- Peripheral neuropathy

- Nail disorders

4.0%

1.4%

3.3%

0%

1.0%

0.5%

0

0

3.3%

4.4%

1.7%

0.6%

1.1%

2.8%

0

0

5.5%5.5%2.8%

3.4%

2.1%

1.4%

0.7%

0

Heidenreich A et al. Eur J Cancer 2014; 50; 1090-99

Abiraterone in post-docetaxel setting significantly

improves survival vs placebo (COU-AA-301)

Fizazi K et al. Lancet Oncol 2012;13(10);983-92

P: prednisone; HR: hazard ratio; CI: confidence interval

22

1195 patients with mCRPC who were previously treated with docetaxel

HR 0.74

(95% CI: 0.64-0.86)

P<0.0001

Ov

era

ll s

urv

iva

l (%

)

Time to death (months)

Placebo+P

11.2 months

Abiraterone acetate+P

15.8 months

100

60

40

20

80

0 6 12 18 24 30

Median age: 69 years

≥75 years: 28%

Abiraterone (COU-AA-301)


SubgroupAA+P

Median (mo)Placebo+P

Median (mo)HR (95% CI)

Baseline ECOG PS*

0–12

17.07.3

12.37.0

0.74 (0.63–0.86)0.77 (0.50–1.17)

Baseline BPI-SF score*

<4≥4

18.413.3

13.99.3

0.69 (0.56–0.85)0.78 (0.63–0.96)

Number of CT regimens*

12

17.114.2

11.710.4

0.71 (0.59–0.85)0.80 (0.61–1.03)

Type of progression*

PSA onlyRadiographic†

18.314.8

13.610.5

0.63 (0.47–0.84)0.78 (0.65–0.93)

Age (years)

<65≥65≥75

15.016.215.6

11.211.19.3

0.69 (0.53–0.91)0.76 (0.63–0.90)0.64 (0.48–0.85)

Visceral disease at entry

YesNo

12.917.1

8.312.3

0.79 (0.59–1.05)0.69 (0.58–0.82)

Baseline PSA >median

YesNo

13.618.2

8.815.3

0.65 (0.53–0.79)0.79 (0.63–0.99)

Baseline LDH >median

YesNo

10.420.8

8.018.0

0.77 (0.63–0.93)0.75 (0.59–0.96)

Baseline ALK-P >median

YesNo

12.419.5

8.118.0

0.60 (0.50–0.74)0.88 (0.69–1.12)

Fizazi K et al. Lancet Oncol 2012;13(10);983-92

BPI-SF: Brief Pain Inventory – Short Form; CI: confidence interval; ECOG: Eastern Cooperative Oncology

Group; LDH: lactate dehydrogenase; OS: overall survival; PSA: prostate-specific antigen23

Favors

AA+P

Favors

Placebo+P

Abiraterone in chemo-naïve patients significantly

improves rPFS but only trend for OS

Overall survivalRadiological PFS

24Ryan C et al. N Engl J Med 2013; 368:138-148

PFS: progression-free survival; P: prednisone

Asymptomatic or mildly symptomatic

chemo-naïve patients without visceral metastases

PF

S (

%)

100

80

60

40

20

00 6 12 18 24 27 303 9 15 21

Months

Abiraterone + P

16.5 mths

OS

(%

)

100

80

60

40

20

00 6 12 18 24 27 30 333 9 15 21

Months

Abiraterone + P

Not reachedPrednisone

27.2 mths

Prednisone

8.3 mths

HR 0.53

(95% CI 0.45–0.62)

P<0.001

HR 0.75

(95% CI 0.61–0.93)

P=0.01

Prespecified P for

significance 0.0035

1088 chemonaive mCRPC patients

Enzalutamide in post-docetaxel setting significantly

improves survival vs placebo (AFFIRM)S

urv

iva

l (%

)

Duration of overall survival (months)

Enzalutamide

OS 18.4 months

Placebo

OS 13.6 months

]

100

90

80

70

60

50

40

30

20

10

0

246 9 12 15 18 2130

HR 0.631

(95% CI: 0.529-0.752)

P<0.0001

Scher HI et al. N Engl J Med 2012;367:1187-97

NYR: not yet reached;OS: overall survival

Median age: 69 years

≥75 years: 25%

1199 patients with mCRPC previously treated with docetaxel

Enzalutamide in chemo-naïve patients

significantly improves rPFS and OS

Overall survivalRadiological PFS

26Ryan C et al. N Engl J Med 2013; 368:138-148

PFS: progression-free survival; P: prednisone

Asymptomatic or mildly symptomatic chemo-naïve mCRPC

0 3 6 9 12 15 18 21

60

50

40

30

20

10

0

90

80

70

100

PF

S (

%)

Enzalutamide

NYR

HR 0.186

(95% CI 0.15–0.23)

P<0.001

Placebo

3.9 mths

Su

rviv

al

(%)

60

50

40

30

20

10

0

90

80

70

100

0 3 6 9 12 15 18 21 24 27 30 33 36

Enzalutamide

32.4 mths

HR 0.706

(95% CI 0.60–0.84)

P<0.0001

Placebo

30.2 mths

1717 chemonaive mCRPC patients; visceral metastases 11%

Enzalutamide (AFFIRM)


SubgroupHR for death

(95% CI)

Median OS (months)

Enzalutamide/Placebo

All subjects0.63 (0.53–0.75) 18.4/13.6

Age (years) <65

>65

0.63 (0.46–0.87)

0.63 (0.51–0.78)

–/12.6

18.4/13.9

Baseline ECOG PS score 0–1

2

0.62 (0.52–0.75)

0.65 (0.51–0.78)

–/14.2

10.5/7.2

Baseline mean

pain score on BPI-SF

<4

≥4

0.59 (0.47–0.74)

0.71 (0.54–0.94)

–/16.2

12.4/9.1

Geographic region North America

Other

0.63 (0.47–0.83)

0.64 (0.51–0.80)

17.4/12/3

–/14.4

Number of prior

chemotherapy regimens

1

≥2

0.59 (0.48–0.73)

0.74 (0.54–1.03)

–/14.2

15.9/12.3

Type of progression

at study entry

PSA only

PSA ±Radiographic

0.62 (0.46–0.83)

0.64 (0.52–0.80)

–/19.5

17.3/13.0

Baseline value

>median value

PSA

LDH

0.62 (0.50–0.78)

0.61 (0.50–0.76)

15.3/10.3

12.4/8.5

Favors

Enzalutamide

Favors

Placebo

Scher HI et al. N Engl J Med 2012; 367: 1187-97

BPI-SF: Brief Pain Inventory – Short Form; CI: confidence interval; ECOG: Eastern Cooperative Oncology

Group; LDH: lactate dehydrogenase; OS: overall survival; PSA: prostate-specific antigen

28

Caution if history of

seizure, brain injury,

cerebral vascular accident,

brain metastases

Cabazitaxel*1

�Higher risk of febrile

neutropenia (7.5 vs 1.3%)

�Higher risk of diarrhea

(6.5 vs 0.3% grade ≥3)

Abiraterone*2

�Hypokalemia, hypertension

& fluid retention due to

mineralocorticoid excess

�Risk of adrenocortical

insufficiency

�Risk of hepatotoxicity

Enzalutamide3

�Higher risk of fatigue

(34% vs 29%)

�Risk of seizures (0.9%)

�Higher risk of hot flushes

(20 vs 10%)

�Higher risk of falls

(4.6 vs 1.3%)

Specific considerations for senior adults

with VERY advanced disease

Product information: 1. cabazitaxel, 2. abiraterone, 3. enzalutamide; Guidelines: 4. EORTC guidelines Aapro M et al. EJC 2011; 47: 8-32 and ASCOCV: cardiovascular; G-CSF: granulocyte colony-stimulating factor; * administered with prednisone

Consider primary

prophylaxis with G-CSF

in high risk patients4

Rehydration with

antiemetics and

antidiarrheals as needed

Use with caution in

patients with CV diseases

Monitor liver function

Caution if interruption of

daily steroids and/or

infection or stress

Evaluate functional

status & program

exercise support

29

Sipuleucel-T significantly improves survival

vs placebo (IMPACT trial, pre-docetaxel)

Main AEs: chills, fever, headache

Ove

rall

su

rviv

al

(%)

Time (months)

Sipuleucel-T

Placebo

Overall survival

12 24 36 48 60 72

0

20

40

60

80

100

0

Median age: 72 years Median age: 72 years

n=512

Hazard Ratio 0.78

(95% CI, 0.62-0.98)

P=0.03

Hazard Ratio 0.78

(95% CI, 0.62-0.98)

P=0.03

Kantoff PW et al. N Engl J Med 2010;363:411-22mCRPC: metastatic castration-resistant prostate cancer; mths: months

Asymptomatic or mildly symptomatic chemo-naïve mCRPC

Without visceral metastases

July 2014 version

Which drug

for which patient?

1 Loriot Y & Fizazi K. Eur Urol 2013; 63: 983-85 ; 2 van Soest R et al. ASCO 2014 (abstract 5043)

TTP: time to progression; mths: months; D: docetaxel plus prednisone; M: mitoxantrone plus prednisone

Docetaxel2AR targeted agents1

Short response to first ADT may predict poor

response to AR-targeted therapies

• Retrospective analysis in 108

patients with metastatic PCa

• Poor response to subsequent

hormone therapies (including

abiraterone, enzalutamide)

if duration of response to

first ADT < 16 months

• Post-hoc analysis of TAX327

randomized phase III trial

• 335 mCRPC patients treated

with docetaxel+P (D) and 336

with mitoxantrone+P (M)

• Good response to docetaxel

irrespective of duration of 1st ADT

Duration of

response

< 16

mths

≥ 16

mths

↓ PSA ≥50% 18% 58%

Median OS - -

Duration of

response

< 15

mths

≥ 15

mths

↓ PSA ≥50% 62% 60%

Median OS

benefit (D vs M)

3.5 mths 2.5 mths

Extended metastatic spread and high NLR may

predict poor response to abiraterone

Leibowitz-Amit et al., Annals Oncol 2014 (epub ahead of print)

NLR: neutrophil/lymphocyte ratio; *Bone mets only or lymph node mets only; **visceral mets alone or combined with bone or lymph nodes

0

10

20

30

40

50

60

0

5

10

15

20

25

30

35PSA response Overall survival

Pe

rce

nta

ge

with

PS

A d

ecre

ase≥5

0%

Media

novera

llsurv

ival(m

onth

s)

Restricted*

mets & NLR≤5

Extended**

mets & NLR >5Other

casesRestricted*

mets & NLR ≤5

Extended**

mets & NLR >5Other

cases

Princess Margaret (test cohort, n=116)

Royal Marsden (validation cohort, n=250)

58

36

6

50

37

20

23

18

14

30

16

11

1. 1. Loriot Y et al. Ann Oncol 2013; 24: 1907-12; 2. 2. Noonan Kl et al. Ann Oncol 2013; 24: 1802-04; 3. 3. Fizazi K et al. Lancet Oncol 2012; 13: 983-92 33

Loriot1 Noonan2 COU-AA-3013

Prior Enzalutamide Yes No Yes No

Median PFS (months) 2.7 6.5 3.6 5.6

Median OS (months) 7.2 11.4 11.8 14.8

↓PSA ≥50%* 8% 29% 3% 29%

Poor response to abiraterone in patients

progressing on enzalutamide (post-docetaxel)

Loriot [1] and Noonan [2] are retrospective studies conducted in 38 and 30 patients,respectively

OS: overall survival; PFS: progression-free survival

*Confirmed by a second value;

34

Poor response to enzalutamide in patients

progressing on abiraterone (post-docetaxel)

*Confirmed by a second value;

Schrader1 Bianchini2 Thomsen3 Badrising4 AFFIRM5

Prior ABI Yes Yes Yes Yes No

Partial response 2.9% 4.3% - 29%

Median PFS,

months

- 2.8 - 3.0 8.3

Median OS,

months

7.1** - 4.8 7.9 18.4

↓PSA ≥50% 29% 13%* 17% 21% 54%*

*Confirmed by a second value; **mean value

1. Schrader A et al. Eur Urol 2014;65:e22-3; 2. Bianchini D et al. Eur J Cancer 2013 (epub ahead of print) 3. Thomsen FB Scand J Urol Nephro 2013 (epub ahead) ; 4. Badrising S. et al. Cancer 2014;120:968-75); 5. Scher HI et al. Lancet Oncol 2012; 13: 983-92

Management of advanced PCa:

specific considerations for senior adults (3/4)




� Zoledronic acid

� Denosumab

� Interventionnal radiology ( vertebroplasty, kyphoplasty )

� Radiation therapy

� Radium-223

• SIOG guidelines

35

0 3 6 9 12 15 18 21 24 27 30 33 36 39

Radium-223 improves survival vs placebo

(ALSYMPCA, post-docetaxel)

Parker C et al. N Engl J Med 2013;369:213-23

%

Placebo (N=307)

Median OS: 11.3 months

Radium-223 (N=614)

Median OS: 14.9 months

100

90

80

70

60

50

40

30

20

10

0

Time to death (months)

Hazard Ratio 0.695

(95% CI, 0.581-0.832)

P=0.00007

Mean age: 70 years

921 patients with symptomatic mCRPC post-docetaxel (or unfit for chemotherapy), ≥2 bone mets, no visceral mets

Matti Aapro

Multidisciplinary Oncology Institute

Genolier, Switzerland

SIOG 2014

prostate guidelines

1. Droz JP et al. Crit Rev Oncol Hematol 2010;73:61-912. Droz JP et al. BJU Int 2010;106:462-9

39

SIOG recommendations for senior adults


40

SIOG recommendations for senior adults

Health status (mainly driven by co-morbidities)

Patient preferences

NOT Chronological age

AND

Treatment recommendations for older men

with prostate cancer should be based on:

Bellara CA et al. Annals Oncol 2012; 23: 2166

G-8 geriatric screening tool

41

0 = severe decrease1 = moderate decrease2 = no decrease

0 = >3kg1 = does not know2 = between 1 &3 kg3 = none

0 = bed or chair bound1 = able to get out of bed/chair but does not go out2 = goes out

0 = severe dementia or depression1 = mild dementia2 = no psychological problems

0 = BMI<191=BMI 19to <212= BMI 21 to <233 = BMI ≥ 23

0 = yes1 = no

0.0 = not as good0.5 = does not know1.0 = as good2.0 = better

0 = >85 yr1= 80-85 yr2 = <80 yr

0-17

A. Has food intake declined over the past 3 months due to loss of appetite, digestive problems, chewing or swallowing difficulties?

B. Weight loss during the last 3 months?

C. Mobility?

D. Neuropsychological problems?

E. BMI (weight in kg/height in m²)

F. Takes more than three prescription drugsper day?

G. In comparison with other people of the same age, how does the patients consider his/her health status?

H. Age

Total score

A fast test• Median 4·4 (± 2.8) minutes

for completion

• 98·7% completion rate in

less than 10 min

A fast test• Median 4·4 (± 2.8) minutes

for completion

• 98·7% completion rate in

less than 10 min

Cut-off value = 14• 14: favourable

• ≤ 14: impairment which

requires comprehensive

geriatric evaluation

Cut-off value = 14• 14: favourable

• ≤ 14: impairment which

requires comprehensive

geriatric evaluation

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>14

No geriatric

assessment

requested

≤14

Geriatric

assessment

requested

Not reversible:• Abnormal IADL

• Abnormal ADL ≥3

• Severe malnutrition

• Cognitive impairment

• Comorbidities CISR-G

grades 3-4

Reversible:• Abnormal ADL: 1 or 2

• Malnutrition

• Depression

• Comorbidities CISR-G

grades 1-2

G8 screening

VULNERABLEFIT FRAIL

GERIATRIC INTERVENTIONSGERIATRIC INTERVENTIONS


43

Principles of the guideline for PCa

Health status evaluation

Readaptation

Standard treatment

as for younger

patients

Standard treatment

as for younger patients

Symptomatic

management including

adapted specific

treatments

Only palliative

treatment

Group 1

(Healthy)

Group 2

(Vulnerable, i.e.

reversible problem

Group 3

(Frail, i.e. non

reversible problem)

Group 4

(Terminal illness)

Geriatric Screening with G-8 tool

18

14.2

10.8

7.9

5.8

4.3

12.4

9.3

6.7

4.7

3.22.3

6.7

4.9

3.32.2

1.5 1

0

2

4

6

8

10

12

14

16

18

20

70 years 75 years 80 years 85 years 90 years 95 years

Me

dia

n l

ife

exp

ect

an

cy (

yea

rs)

Top 25th percentile 50th percentile Lowest 25th percentile

Walter LC et al. JAMA 2001;285:2750-6

EAU and NCCN recommend therapy of early asymptomatic

disease in all patients with life expectancy > 10 years

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Should be considered for

therapy:• ‘Fit’ and ‘vulnerable’

aged 70-80 years

• Only ‘fit’ aged 80-85 years

EAU / SIOG 2014 guidelines Individualized treatment

and life expectancy evaluation is mandatory

Mottet N et al. EAU guidelines 2014 (www.uroweb.org)Droz JP, et al. Lancet Oncol 2014 (In press)

Overall conclusions

• Docetaxel (without prednisone) provides benefitversus ADT alone in metastatic hormone-naive PCa(unapproved indication )

• Many new drugs to manage metastatic CRPCin senior adults, representing a significant increase in healthcare expenditure

• Optimal timing, sequencing and potential combinationsof these new agents remain to be determined

• Need to rely on currently available predictorsof response to each drug to optimize patient management

DECEMBER 5: A JOINT MASCC SIOG SESSION

Chairs: D. Keefe (AUS) ; G. Zulian (CH)

…Bone health: a key factor in elderly and not so elderly patients with cancer M. Aapro

(CH)

…Mucositis and new drugs: to prevent or to treat? D. Keefe (AUS)

…Depression: an issue in survivorship for elderly cancer patients. L. Balducci (USA)

…Ovarian cancer: issues in the long term for elderly patients C. Steer (AUS)

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Matti Aapro

IMO Genolier (Switzerland)

THANK YOU MERCI

Any questions?

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management of advanced prostate cancer in senior … · advanced prostate cancer in senior adults:...

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