Download Selecting ADj Rx Elders - UNC Lineberger Comprehensive Cancer

Addressing the Needs of Breast Cancer
Patients Ages 70 and Older
UNC Telehealth Series; February 10, 2016
Hyman B. Muss, MD
Objectives
 Discuss
the complexities of the older patient in regard
to defining patient function and life expectancy.
 Evaluate
and define the goals of therapy as well as
assess the risks and benefits of adjuvant systemic
therapy.
 Compose
a plan of action for helping to manage
metastatic disease in elderly breast cancer patients.
The Tsunami of Cancer and Aging
U.S. Estimated Life Expectancy
1. Estimated life expectancy at birth in years, Deathregistration States, 1900–28, and United States, 1929–2002
90.0
80.0
70.0
60.0
2009
All 79 years
Women: 81
Men: 76
1935
40.0
1918
30.0
20.0
10.0
Year
2000
1996
1992
1988
1984
1980
1976
1972
1968
1964
1960
1956
1952
1948
1944
1940
1936
1932
1928
1924
1920
1916
1912
1908
1904
0.0
1900
Age
50.0
Estimated Life-Expectancy of Women by Age and Comorbidity
Remianing life-epxtectancy - years
20
18
Comorbidity
16
14
None
12
10
low/medium
8
high
6
4
2
0
70
75
80
Age
85
90
Low/medium: diabetes or myocardial infarction or others.
High comorbidity: COPD or congestive heart failure or others
Modified from Cho et al,. Ann Intern Med. 2013;159(10):667-76
Why is Geriatric Oncology Important ?
US Population 65 and older
20
12
12.6
13.1
9.5
1965
1985
1990
2005
2030
SEER 2002-2006: Breast Cancer
Incidence and Mortality Rates
300
250
Average Age ~ 61
200
150
Incidence
Mortality
100
50
0
25-9
35-9
45-9
55-9
65-9
75-9
85+
http://seer.cancer.gov/cgi-bin/csr/1975_2006/search.pl
Breast Cancer 2013
Incidence
Mortality
CA: A Cancer Journal for Clinicians
pages 52-62, 1 OCT 2013 DOI: 10.3322/caac.21203
U.S. Breast Cancer Death Rates Over Time
Smith B D et al. JCO 2011;29:4647-4653
Selecting Cancer Treatment in
Older Patients
Estimate Life Expectancy
eprognosis.ucsf.edu
Define Goals of Treatment
not always longevity..
Calculate Benefits/Risk of
Treatment
Schonberg Index
All cause 5 and 9 yr mortality
Variable
Patient 1
Patient 2
Age
75
75
Sex
Female
Female
smoking
never
former
BMI
30
23
History of Ca
No
No
Diabetes
No
Yes
COPD
No
Yes
Hospitalizations past year
None
Once
Self rated health
excellent
fair
Dependent IADL
none
1
Difficulty walking 1/4 mile
No
Yes
5 and 9 year Mortality Risk
6% and 16%
43% and 75%
http://eprognosis.ucsf.edu/
What’s the goal of treatment?

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
Preferences of Seriously Ill
I would rather die
than have a treatment
that causes:
100
90
80
70
60
50
40
30
20
10
0
Percent
89
74
11
A High Functional Cognitive
Burden
loss
Loss
Fried et al, NEJM 2002
N=226 with cancer, COPD, ASCVD
The Value of Geriatric Assessment
Uncovers problems not found routinely
 Many problems have beneficial interventions

– Improve function
– Quality of life
– Survival
Allows for accurate life-expectancy estimate
 Can predict cancer related toxicity

Brief Geriatric Assessment: 0916
DOMAIN
ASSESSMENT MEASURE
Health Professional
Functional
Status
Co-morbidity
Cognition
Activities of Daily Living (ADL)
Timed Up and Go
Instrumental Activities of Daily Living
KPS- Physician Rated Karnofsky Self Reported
No. of Falls in the last 6 months
10
Blessed
Orientation
minutes
Memory-Concentration
Psychologic
Number /Type of Comorbid Conditions
No. of Medications
Vision and Hearing Assessment
20-30
minutes
Mental Health Index-17
Social Activity Limitation Measure (MOS)
Social Support Survey (MOS)
Social
Nutrition
Self Reported
BMI
Unintentional Weight Loss 6 mths
Is cancer the patient’s
major illness?
Karnofsky performance status ≥80
GA identified deficits (n=984, mean age 73, Age 65-99)
Trevor A. Jolly et al. The Oncologist 2015;20:379-385
Falls in UNC Cancer Patients
Outcomes
N=70 (100%)
95% CI
Falls Documented
2 (3%)
0-10%
Gait Assessment
19 (13%)
10-30%
2 (3%)
0-10%
19 (13%)
10-30%
Referrals
Vitamin D Level




24% of the the patients in the registry reported 1 or more fall in the past 6 months
54% had one fall and 47% had two or more falls
No more than 10% of patients who experience falls have appropriate medical record
documentation or referrals.
Older adults who fall were not adequately evaluated by medical oncologists.
Guerard et al, ASCO 2014; JOP 2015
“If your time hasn’t
come yet,
not even a doctor
can kill you.”
Leigh Stoecker
IASIA
Predictive Model
Risk factors for Grade 3-5 Toxicity
OR (95% CI)
Score
Age ≥73 yrs
1.8 (1.2-2.7)
2
GI/GU cancer vs. other cancer
2.2 (1.4-3.3)
3
Standard dose vs. reduced
2.1 (1.3-3.5)
3
Polychemotherapy vs. single agent
1.8 (1.1-2.7)
2
Hemoglobin (male: <11, female: <10)
2.2 (1.1-4.3)
3
Creatinine Clearance (Jelliffe –ideal wt) <34
2.5 (1.2-5.6)
3
1 or more falls in last 6 months
2.3 (1.3-3.9)
3
Hearing impairment (fair or worse)
1.6 (1.0-2.6)
2
Limited in walking 1 block (MOS)
1.8 (1.1-3.1)
2
Assistance required in medication intake
1.4 (0.6-3.1)
1
Decreased social activity (MOS)
1.3 (0.9-2.0)
1
Possible score range: 0-25; ROC 0.72
Hurria JCO 29:3457, 2011
Ability of (A) risk score versus (B) physician-rated
Karnofsky performance status (KPS) to predict
grade 3-5 chemotherapy toxicity.
Hurria A et al. JCO 2011;29:3457-3465
©2011 by American Society of Clinical Oncology
Optimizing
Adjuvant Treatment ?
Selecting Adjuvant Therapy:
“3” Types of Breast Cancer
Type/Frequency
Treatment
Comment
Hormone Receptor
Positive ER and/or PR)
AND HER-2 negative
(about 70% of pts)
Endocrine therapy for
most
Chemotherapy for some
New Genetic based
assays can help select
who needs
chemotherapy
Most relapse > 5 years
HER-2 positive
ANY ER or PR
(About 15% of pts)
Chemotherapy AND antiHER-2 therapy for most
Endocrine Rx if hormone
receptor positive
Major improvements in
outcome with
anti-HER-2 Rx
Most relapse < 5 years
Chemotherapy for most
More common in
younger pts and A-A pts
More chemo is better
Most relapse < 5 yrs
ER AND PR
AND HER-2 negative
“triple negative:
(About 15% of pts)
Adjuvant Endocrine Therapy Older Pts

Risk reductions
– 30% for mortality
– 50% for recurrence
AI or Tam>AI (or Tam?)
 Not all patients need it

– Low risk for recurrence
– Short life-expectancy

Adherence and Compliance key
Letrozole vs Placebo 70+
Letrozole = 681; Placebo = 642
50
45
45 44
40
35 36
35
30
25
20
15 14
13
15
10
10
5
5
5
1
1
0
Fatigue
Nausea
Depression Arth+Myal
Letrozole
Vag
Dryness
↑ cholest
Placebo
Muss et al NCIC MA17 JCO 2008 (QOL slight inc bodily pain, vasomotor at 2 years)
Just imagine what the data
would look like if patients
actually took their medications.
Rules of Thumb
Adjuvant Chemo Older Patients
Percent Improvement 10year Overall Survival
Action
<3%
No Chemotherapy
3-5%
Chemotherapy for some
>5%
Consider based on life
expectancy and goals
What Chemotherapy?
Adjuvant online and
Predict +
• 1st Generation
AC = CMF = FEC6 (B-36)
Q2w paclitaxel x 4 (40101)
• 2nd Generation
TC x 4
FAC or FECx6; not so sure
• 3rd Generation
Anthracycline + taxane
Caveats
• Proportional
reductions key
but not verified
in older women
• AML/MDS,
cardiac toxicity
higher in
elders.
10 year all cause mortality
75 year old, ER+, 1-2 cm, grade 2
70
Average health
60
60
50
50
None
Endo
E+1st
E+2nd
E+3rd
40
30
20
40
30
10
0
0
4-9+
LN
None
Endo
E+1st
E+2nd
E+3rd
20
10
No
1-3+
Nodes LN
Poor health (+10)
Non BC death
70
No
1-3+
Nodes LN
4-9+
LN
From www.adjuvantonline May 2012
Hospitalizations with Adjuvant Chemotherapy
A: All B: Adjusted for growth factors
CMF 14% >65. Barcenas et al. JCO 2014;32:2010-2017
Anti-HER-2 Rx in Elderly

Estimate survival
– Treat like younger if > 5yrs

Cardiology consult if CHF risk factors
– Consider proactive β-blocker or ACE inhibitor

What about anti-HER 2 therapy alone?
– ATEMPT: TDM-1 vs paclitaxel/trastuzumab
– Freedman for Alliance/ACCRU
– Ado-trastuzumab emtansine (TDM-1)
• Pts who decline chemo/T or docs afraid to give it
• ≥65, Stage 1-3, q3 wks x 1 yr, GA, biomarkers
Probabilities of Disease-free Survival and Recurrence-free Interval.
Stage 1 HER2+ BC: paclitaxel + trastuzumab
Tolaney SM et al. N Engl J Med 2015;372:134-141
Tolaney SM et al. N Engl J Med 2015;372:134-141
Most Common Adverse Events Occurring during Protocol Therapy.
Tolaney SM et al. N Engl J Med 2015;372:134-141
Predict plus (UK) for HER-2 +
http://www.predict.nhs.uk
75, screen detected, 2.0 cm, grade 2
N-, second generation chemotherapy
ER-
ER+
Therapy for Metastases in Older Patients
Type/Frequency
Treatment Strategy
Hormone Receptor
Positive ER and/or PR)
AND HER-2 negative
(about 70%)
Endocrine therapy for most until certain not
working AND symptoms
THEN Chemotherapy
HER-2 positive
ANY ER or PR
(About 15%)
Hormone Receptor Positive: Endocrine Rx
with concurrent or sequential anti-HER-2
therapy OR
Anti-HER- 2 Rx usually with chemotherapy
ER AND PR
AND HER-2 negative
“triple negative:
(About 15%)
Chemotherapy
Kindler, Gentler Chemotherapy
Capecitabine
 Low-dose cyclophosphamide/methotrexate
 Weekly taxanes
 Eribulin
 Liposomal doxorubicin
 Weekly anthracyclines
 Vinorelbine
 Gemcitabine

Yow 1410 (BCRF 1334) Trial Design
Assessments
Randomiz
e
Age ≥ 65 years
Stage 1-3 Breast Cancer
Chemotherapy completed
p16INK4a Pre, 6 months, one year
Lean Body Mass (Dexa) Pre, 6 months, one year
Geriatric Assessment/Questionnaires
Activity and Sleep tracker: continuous
Control
PRE
Physical
Activity
3
6
12
Time/Months
Walking
Concurrent RO-1 trial without exercise
intervention will serve as control
Metrics – What We Measure
Metric
Measure
Description
Measures function (physical and mental),
other diseases, anxiety, depression,
nutrition and social support
Exercise and Alcohol Use
Geriatric Assessment (CARG)
Health Behavior Questionnaire
Short Physical Performance Battery
Engagement in Physical Activity
OEE/Outcome Expectations for Exercise
FitBit (data capture throughout chemotherapy)
Physical activity log daily during chemotherapy
Physical function
CBC, renal, hepatic, albumin
Basic organ function
Biomarkers (p16, IL-6, D-Dimer, CRP
Markers of inflammation and aging
DEXA scan for Muscle mass
CTCAE (during chemotherapy)
Lean body mass and fat mass
Side effects of treatment – MD reported
PRSM (PRO – during chemotherapy
Patient reported side effects
FACT-Breast
Quality of life
FACIT-Fatigue
PSEFSM/Perceived Self-Efficacy for Fatigue SelfManagement
Fatigue
Program satisfaction
January 2016
Thank
You