Elderly Cancer 2013-2014

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12 Νοε 2013 (πριν από 4 χρόνια)

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Case
-
Based Learning

CME/CE ACCREDITATION BY

Arti

Hurria
, MD

City of Hope

Duarte, CA


Hyman B. Muss, MD

University of North Carolina

Chapel Hill, NC

PROGRAM CO
-
CHAIRS

Elderly Cancer 2013
-
2014

Breast Cancer: A Model for Treating
Solid Malignancies in the Elderly


Hyman
B. Muss, MD


Breast

Cancer


Breast cancer like
most human cancers
is a disease of aging!

SEER 2002
-
2006: Breast Cancer
Incidence and Mortality Rates

0
50
100
150
200
250
300
25-9
35-9
45-9
55-9
65-9
75-9
85+
Incidence
Mortality
http://seer.cancer.gov/cgi
-
bin/csr/1975_2006/search.pl

Average Age ~
61

Smith B D et al. JCO 2011;29:4647
-
4653

©2011 by American Society of Clinical Oncology

Breast cancer death rates for the US 1980 to 2007
normalized to the group specific death rate in 1990


Early stage breast cancer


Adjuvant therapy to increase cure


Treatment should not be as bad as disease


Metastatic disease


“You can’t improve on being asymptomatic.”


Maintain QOL and function first


Improve symptoms when present


Provide “structured” palliative care

What‘s the goal of treatment?

Case: A 78 year old female…


Mammographically detected tumor


Lumpectomy and SLN biopsy


1.4 cm grade 2 IDC, LVI neg


ER 86%, PR 67%, HER2 negative


SLN negative (0/3)


Describes
her general health as “good”


Full ADL and most IADLs. No falls.

What is the likelihood that she will die
of breast cancer in next 10 years if you
treat her with endocrine therapy only?

1
2
3
4
44%
3%
18%
34%
1.
< 10%

2.

About 25 %

3.

About 50 %

4.

About 75 %

Cause of Death After ~ 28 Year Follow

White Women
≥ 70 With Breast Cancer

[395,000 patients 1973
-
2000]

0
20
40
60
80
100
In situ
Local
Regional
Metastases
percent

Breast Cancer
Non-Breast Cancer
Schairer

et al, SEER data, JNCI 96:1311, 2004

A word on radiation..

Do all patients with hormone
receptor positive early stage
breast cancer need breast
radiation?

CALGB
9343

Hughes et al ASCO 2010



ELIGIBILITY


Age
³

70


Clinically


Node Negative


Lumpectomy,


Negative Margin



Tumor size


<=

2 cm


ER Positive or


Indeterminate



STRATIFICATION


Age


< 75


>=75


Axillary Dissection

Yes

No




Radiation +

Tamoxifen

(n=317)




Tamoxifen

(n=319






R

A

N

D

O

M

I

Z

E










Median follow = 12 years

CALGB 9343

CALGB 9343 10 years

Tam + RT

N=317

Tam Alone

N=319

p

Breast Recurrence

2%

9%

<.01

Ultimately had
mastectomy

2%

4%

NS

Second primary cancer

12%

9%

NS

Distant

metastases

5%

5%

NS

Death

33%

33%

NS

Death due to Breast Ca

4%

3%

NS

EBCTCG Lancet 2005: RT or Not

Breast Cancer Mortality Risk %

5 yr Reduction
in Local

Recurrence

5yr risk

Active

vs.
Control

5yr

Absolute

Reduction (SE)

15yr risk

Active vs.
Control

15

yr

Absolute
Reduction (SE)

<10%

18.9 vs.

19.5

0.6 (0.6)

41.3 vs. 42.3

1.0 (0.9)

10
-
20%

21.8 vs. 23.3

1.5 (0.6)

44.0 vs. 48.5

4.5 (0.8)

>20%

24.9 vs.

26.7

1.8 (1.3)

47.4 vs. 53.4

6.0 (1.6)

>10%

22.4 vs. 24.0

1.6 (0.6)

44.6 vs. 49.5

5.0 (0.8)

Case: A 75 year old female…


Mammographically detected tumor


Lumpectomy and SLN


3.2 cm grade 2 IDC, LVI neg


ER 87%, PR 17%, HER2 negative


SLN negative 0/3


Describes
her general health as
“excellent””


Upset that you are late since she will miss
her tennis lesson.

In addition to radiation and endocrine
therapy what else would you
recommend?

1
2
3
4
39%
0%
23%
38%
1.
Nothing

2.
21 gene assay

3.
Chemotherapy

4.
Other

Why?


Overall chemo of minimal or no value


Some pts benefit however


Healthy 75 y/o average survival 12 yrs +


21 gene assay can select the 5
-
10% with
high scores who may benefit

ER and/or PR + and HER
-
2 negative


Most common phenotype of breast cancer


Increases with age


About 75% of those 75 and older


Variable course


Luminal A and B


Most recurrences after 5 years


Endocrine therapy mainstay for most

Without endocrine therapy

Saphner
, et al. JCO 1996

Annualized Hazard of Recurrence after


Breast Cancer Diagnosis:

Analysis by Hormone Receptor Status

Is there any role for
chemotherapy in older hormone
receptor positive, HER
-
2
negative patients?

Chart


EBCTCG
2006

15 year BC Mortality (%)

Type Rx

Decrease
#

12.5%

Low risk N
-

25%

Higher risk
N
-

50%

Node

Positive

Risk

Gain

Risk

Gain

Risk

Gain

None

12.5

-

25

-

50

-

Tamoxifen

Any Age

31%

9

4

18

7

38

12

Anthracyline*

+

tamoxifen

Age 50
-
69

45%

7

5

15

10

32

18

From EBCTCG Lancet 2005 (365:1687)

*Anthracycline about 6 mths of FAC or FEC

#
Decrease is proportional reduction and risk/gain rounded off

Sparse data in 70+ but seems similar in magnitude

Results: Recurrence Score the Rate of Distant
Recurrence Increases by Node Status

0

10

20

30

40

50

60

70

80

90

100

9
-
Years Risk of Distant Recurrence (%)


0


5


10


15


20


25


30


35


40


45


50

Recurrence Score

Node

Negative

1
-
3
Positive

Nodes

4+ Positive

Nodes

95%CI

Mean

Dowsett et al., SABCS 2008,
JCO 2010

TAM or Al No chemotherapy

Case: A 76 year old female…


Felt a right breast mass


3 cm on exam and suspicious nodes


Lumpectomy and SLN → Ax dissection


3.2 cm grade 3 IDC, LVI positive


ER 0%, PR
0
%, HER2 negative


4/15 positive nodes


Well controlled hypertension


LVEF 59%

Triple negative breast cancer



About 15% of elders


Biology similar irrespective of age


Most recurrences within 5 years


More chemo is better


Taxanes

and
Anthracyclines


Estimating life expectancy and toxicity key

In addition to local
-
regional radiation
what chemotherapy would you
recommend?

1
2
3
4
5
5%
31%
2%
45%
17%
1.
CMF

2.
TC for four cycles

3.
TC for 6 cycles

4.
Anthracycline and
t
axane

(DD AC>T,TAC)

5.
Other






www.adjuvantonline.com

Adjuvantonline: Chemotherapy


First Generation



AC x 4


CMF


Second Generation


TC (docetaxel and cyclophosphamide)


FEC or FAC x 6


Third Generation


Dose dense AC and paclitaxel


TAC


PACS 001: CA x 3 then docetaxel x 3


May overestimate Rx value in elders older

76
yo

g3 TN 3.2 cm 4+LN

with minor problems

Lives saved per 100
pts by regimen

60% die of breast
cancer

1
st

generation


(CMF or 4 AC)

4.3%

2
nd

generation


(TC x 4 or CAF, CEF x6)

9.9%

3
rd

generation


(TAC, DDAC
-
paclitaxel,

PACS 001)

15.0%

Copyright restrictions may apply.
Muss, H. B. et al. JAMA 2005;293:1073
-
1081.
Overall Survival for All Patients by Chemotherapy Intensity and
Age Group
Chart

CMF;
Cyc

100 day 1
-
14, MTX 40
and FU 600 d1,8
Q4W

AC
;
Dox

60,
Cyc

600 d1 Q3W

CMF 6 cycles or
AC 4 cycles

Capecitabine
(X) for 6
cycles

Randomize

Stratification

Age 65
-
69,70
-
80,80+; PS 0
-
1 vs 2;HER
-
2 +/
-
/
unk

2000 d1
-
14 Q3W

All doses per M2

Muss et al NEJM 2009 360:2055

CALGB 49907
-

Design

Unplanned Subset Analysis

Years From Study Entry
Proportion Relapse-Free
0
1
2
3
4
5
0.0
0.2
0.4
0.6
0.8
Relapse-Free Survival
By Arm
Receptor-Negative Tumors
CMF/AC
Capecitabine
N= 106
N= 97
Events= 14
Events= 34
Years From Study Entry
Proportion Surviving
0
1
2
3
4
5
0.0
0.2
0.4
0.6
0.8
Overall Survival
By Arm
Receptor-Negative Tumors
CMF/AC
Capecitabine
N= 106
N= 97
Events= 9
Events= 22
Years From Study Entry
Proportion Relapse-Free
0
1
2
3
4
5
0.0
0.2
0.4
0.6
0.8
Relapse-Free Survival
By Arm
Receptor-Positive Tumors
CMF/AC
Capecitabine
N= 218
N= 209
Events= 21
Events= 26
Years From Study Entry
Proportion Surviving
0
1
2
3
4
5
0.0
0.2
0.4
0.6
0.8
Overall Survival
By Arm
Receptor-Positive Tumors
CMF/AC
Capecitabine
N= 218
N= 209
Events= 15
Events= 16
Unplanned Subset Analysis

RFS in ER+

RFS in ER
-

OS in ER+

OS in ER
-

Muss et al NEJM 2009 360:2055

Unplanned Subset Analysis

5
-
14
-
09 CALGB 49907

Courses Received (%)

0
10
20
30
40
50
60
70
80
90
100
%
1
2
3
4
5
6
Capecitabine
CMF
AC
N=90

Node negative

ER and PR negative

RCT CMF v none

12 year follow

Iv CMF q3wks x 12

600/40/600 m2

OS 80% vs 50%


Zambetti

Bonadonna

Ann
Oncol

1996 7:481

Zambetti

Case: A 78 year old female…


Felt a left breast mass


3 cm on exam and suspicious nodes


Lumpectomy and SLN → Ax dissection


2.8 cm grade 3 IDC, LVI negative


ER 0%, PR
0
%, HER
-
2 positive


3
/15 positive nodes


Well controlled hypertension, DM. Full ADL


LVEF 54%

In addition to local
-
regional radiation
and trastuzumab what chemotherapy
would you recommend?

1
2
3
4
20%
2%
39%
39%
1.
Anthracycline and
taxane

2.
Docetaxel and
carboplatin

3.
Docetaxel and
cyclophosphamide (TC)

4.
Other

Slamon SABCS 2009

Chart

Chart

Chart

Assess First, Then Treat


Good shape
:

Same treatment as younger



Vulnerable:


Intervention > standard Rx



Frail:


Intervention >adapted
treatment or palliation



“Too sick”

Standard

treatment

Geriatric

intervention

Metastatic Disease 2012


All therapy is palliative


Survival depends mostly on tempo


Biology of tumor key


Median is 18
-
24 months


SEER 2011: 20
-
25% alive at 5 years


Goal of treatment


Control of disease and symptoms


Maximizing quality of life

Case: A 78 year old female…


Stage 3A ER+, HER2 neg BC 4 years ago


Now with slowly progressive bone and
small liver mets.


Refractory to all endocrine therapy


Pain in T3 “5 out of 10” on opiates


Problems with constipation and appetite


Can dress herself but needs help with IADL


Thinks you are Brad Pitt

In addition to local
-
regional radiation
and what chemotherapy would you
recommend next?

1
2
3
4
34%
1%
57%
7%
1.
Single agent
chemotherapy

2.
Combination
chemotherapy

3.
“Structured” palliative
care consultation

4.
Other

Early Palliative Care in
Metastatic Lung Cancer


151 pts newly diagnosed metastatic NSCL


PS 0
-
2


~28% brain mets and 99% chemotherapy


Randomized: early palliative care vs not


Intervention: Met with Board
-
certified
palliative care MD within 3 wks of enrollment
and then at least monthly

Temel

NEJM 2010

Twelve
-
Week Outcomes of Assessments of Mood

Temel

JS et al. N
Engl

J Med 2010;363:733
-
742

Chart

Kaplan

Meier Estimates of Survival According to Study Group

Temel

JS et al. N
Engl

J Med 2010;363:733
-
742

Median 8.9 vs 11.6 months

P = 0.02

Temel

Case: A 78 year old female…


It’s 4 weeks after RT


PS now 1, Pain 3 out of 10 without opiates


Grade 2 fatigue


No change in ADL or IADL


Palliative care has tuned her up


AST, ALT,
Alk

Phos

slowly increasing


PET/CT clear progression over 4 mths


She knows who you are

What would you do now
?

1
2
3
4
69%
3%
23%
5%
1.
Single agent
chemotherapy

2.
Combination
chemotherapy

3.
Encourage her to
consider hospice

4.
Other

Metastatic BC: Kinder, Gentler Rx


capecitabine (start low)


Weekly anthracyclines or liposomal doxorubicin


Low dose
po

cyclophosphamide/
mtx


Weekly taxanes


eribulin
, gemcitabine,
vinorelbine


HER2 positive


Single agent trastuzumab (
±

lapatinib?)


Chemo+trastuzumab
, lapatinib, pertuzumab

Several of these agents are not approved by the FDA for
use
in metastatic
breast cancer in the United States

Eribulin and Age

Data from EMBRACE


RCT E vs best pick


762 patients


508 to eribulin


44 ≥ 70 years


Toxicity similar
among age cohorts


Similar results with
expanded data set

RFS and age

Twelves et al ASCO 2011: abst 1060

Nab
-
paclitaxel and age

Metastatic BC



Age 30
-
81 (n=29)



100/m2 wk for 3 wks/4


15 pts 60
-
69, 9 at 70+


1
st

or 2
nd

line


PR 31%, SD 38%


Dose reductions 62%


Dose delays 21%

Treatment well tolerated
among all age groups

Hurria SABCS 2011 Abst 71:586s

Metastatic Breast Ca Elderly


Keep focused on goals


“Structured” palliative care


Hormone Receptor (HR) positive


Endocrine therapy until certain not working


For Endocrine refractory or HR negative


Single agent sequential therapy


HER2+ anti
-
HER2 therapy and usually chemo


You can’t improve on being asymptomatic!

Monalisa

“Before I came here I was
confused about this topic.
Having listened to your lecture
I am still confused, but on a
higher level.”

Enrico Fermi,1938

Nobel Laureate in Physics

Thank You!

UNC


North Carolina Cancer
Hospital

UNC


Lineberger
Comprehensive Cancer
Center