Transcript Lung.Temel.7509

Early palliative care improves quality of life,
reduces aggressiveness of care at the end-oflife and prolongs survival in stage IV NSCLC
patients:
Results of a phase III randomized trial
Temel JS, Greer JA, Gallagher E, Admane S, Pirl WF,
Jackson VA, Dahlin C, Muzikansky A, Jacobsen J, Lynch TJ
Study Rationale
Current Care Model
Proposed Care Model
www.iom.edu
Integrated Oncology and Palliative Care in the
Ambulatory Care Setting
50 patients with newly
diagnosed metastatic
NSCLC
Meet with palliative care
at least monthly during 1st
6 months of care
Temel, JCO (25)17,
Study Design
150 patients
with newly
diagnosed
metastatic
NSCLC
Baseline
Data
Collectio
n
R
A
N
D
O
M
I
Z
E
D
Early palliative
care integrated
with standard
oncology care
Standard oncology
care
Meet with palliative
care within 3 weeks
of signing consent
and at least
monthly thereafter
Meet with palliative
care only when
requested by
patient, family or
oncology clinician.
Early Palliative Care Study Procedures
Palliative Care Guidelines
Illness understanding and education
Inquire about illness and prognostic understanding
Offer clarification regarding treatment goals
Symptom management
Pain
Pulmonary symptoms
Fatigue and sleep disturbance
Mood
Gastrointestinal
Decision-making
Assess mode of decision-making
Assist with treatment decision-making
Coping with life-threatening illness
Patient
Family/family caregivers
www.nationalconsensusproject.or
Study Objectives
Primary Objective:
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Measure the difference in QOL between the two
study arms at 12 weeks.
Secondary Objectives:
1. Psychological distress at 12 weeks
2. Quality of end-of-life care
3. Resource utilization at the end-of-life
4. Documentation of resuscitation preference in
the medical record
Study Eligibility
Metastatic NSCLC diagnosed within the
previous 8 weeks.
2. ECOG performance status 0-2.
3. Ability to read and respond to questions
in English.
4. Planning to receive oncology care at the
participating institution.
1.
Study Measures
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Quality of life
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FACT-Lung - Lower scores indicative of greater symptom
burden
Lung Cancer Symptom (LCS): lung cancer specific symptoms
 Trial Outcome Index (TOI): LCS and functional and physical wellbeing
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Psychological Distress
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Hospital Anxiety and Depression Scale (HADS)
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Score of > 8 of each subscale indicative of symptoms of
depression or anxiety
Patient Health Questionnaire-9 (PHQ-9)
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Evaluates symptoms of major depressive disorder (MDD) using
DSM-IV criteria.
Data Collection
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Measures of health care utilization were
collected from electronic medical
records.
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Use of anti-cancer therapies
Hospital and emergency room visits
Dates of hospice referral
Date and location of death
Documentation of resuscitation preference
Sample Size Calculation
Sample size was calculated to detect a
clinically meaningful change in QOL,
defined as a medium effect size of 0.5
SD.
 120 patients were required to have 80%
power to detect an effect size of 0.5 SD
in FACT-Lung TOI.
 Due to rapid accrual, the study was
amended to add an additional 30
patients.
 Data were analyzed through 12/1/09.
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Statistical Analysis
Differences between study arms in clinical
outcomes were assessed with two-sided Fisher’s
Exact tests for categorical variables and
independent-samples t-tests for continuous
variables.
 For ITT analyses, baseline values were carried
forward for missing patient-reported outcome
data.
 Survival time was calculated from the date of
consent to date of death using the Kaplan-Meier
method.
 Differences in survival were tested with Log
Rank and Cox Proportional Hazard Model.
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Study Flow
Assessed for eligibility (N=283)
June 2006 – July 2009
Excluded (n=9)
Not offered (n=60)
Refused to participate (n=59)
Study closed during eligibility
(n=4)
Randomly assigned
(N=151)
Palliative care (N=77)
Standard care (N=74)
12 week QOL assessment:
60 completed (78%)
10 died (13%)
7 not completed (9%)
12 week QOL assessment:
47 completed (64%)
17 died (23%)
10 did not complete (13%)
Patient Demographics
Sample Demographics
Standard Care
N=74
Mean (SD) or N (%)
Early Palliative Care
N=77
Mean (SD) or N (%)
pvalue
64.9 (9.4)
65.0 (9.7)
0.94
Female
36 (49)
42 (55)
0.47
Race
White
African American
Asian
70 (95)
3 (4)
1 (1)
77 (100)
0 (0)
0 (0)
0.06
1 (1)
1 (1)
1.00
45 (61)
9 (12)
12 (16)
8 (10)
48 (62)
9 (12)
12 (16)
8 (10)
1.00
Age Mean (SD)
Ethnicity
Hispanic
Marital Status
Married
Single
Divorced/Separated
Widowed
Baseline Clinical Characteristics
Clinical Characteristics
Standard Care
N=74
N (%)
Early Palliative
Care
N=77
N (%)
p-value
ECOG PS:
0
1
2
30 (41)
35 (47)
9 (12)
26 (34)
46 (60)
5 (6)
0.24
Brain Metastasis:
Yes
No
19 (26)
55 (74)
24 (31)
53 (69)
0.46
Initial Anticancer Therapy:
Platinum-Based Regimen
Single Agent Chemotherapy
Oral EGFR-TKI
Radiation
Both Chemo and Radiation
No Chemotherapy
35
3
6
26
3
1
(47)
(4)
(8)
(35)
(4)
(1)
35 (45)
9 (12)
6 (8)
27 (35)
0 (0)
0 (0)
0.82
35 (75)
12 (25)
36 (72)
14 (28)
0.78
Type of Initial Chemotherapy
Regimen:
Standard Therapy
Clinical Trial
Baseline Quality of Life and Psychological
Distress
Variable
Standard Care
M (SD) or N (%)
Early Palliative Care
M (SD) or N (%)
p-value
91.7 (16.7)
93.6 (16.5)
0.50
55.3 (13.1)
56.2 (13.4)
0.67
Depression
18 (25)
17 (22)
0.67
Anxiety
24 (33)
28 (36)
0.70
12 (17)
9 (12)
0.40
FACT-Lung
Trial Outcome Index (TOI)
HADS Symptoms
Major Depressive Disorder
Palliative Care Visits by 12 Weeks
Palliative Care Visits
Standard Care (N=74)
N (%)
Early Palliative Care (N=77)
N (%)
None
64 (87)
1 (1)*
1
7 (9)
0
2
3 (4)
8 (10)
3
0
18 (23)
4
0
26 (34)
>5
0
24 (31)
* Died within 2 weeks of enrollment
12-week Quality of Life Measures
Variable
FACT-Lung
Lung Cancer Symptoms
(LCS)
Trial Outcome Index (TOI)
Standard Care
N=47
M (SD)
Early Palliative
Care
N=60
M (SD)
Effect
Size
p-value
91.5 (15.8)
98.0 (15.1)
0.42
.03
19.3 (4.2)
21.0 (3.9)
0.42
.04
53.0 (11.5)
59.0 (11.6)
0.52
0.009
(Cohen’s d)
Effect of Early PC on 12-week Psychological
Distress
60
50
40
p=0.01
p=0.66
30
Standard Care
Early Palliative Care
p=0.04
20
10
0
Depression
Major Depressive
Disorder
Anxiety
Change in QOL from Baseline to 12 Weeks
FACT-Lung
Mean change Early Palliative Care = +
4.2
Mean change Standard Care = - 0.4
p=0.09
FACT- Lung TOI
Mean change Early Palliative Care = +
2.3
Mean change Standard Care = - 2.3
p=0.04
Quality of EOL Care and Resource
Utilization
ASCO Quality Measures
No hospice
2. Enrolled in hospice < 3 days before death
3. Chemotherapy within 14 days of death (DOD)
1.
Measure
Standard Care
N (%) or Median
Early Palliative Care
N (%) or Median
p-value
Aggressive EOL Care
No hospice
Hospice < 3 days
Chemo within 14 DOD
30 (54)
22 (39)
5 (15)
12 (24)
16 (33)
15 (31)
1 (3)
7 (18)
0.05
Hospital/ER Admissions within 30
DOD
31 (55)
19 (39)
0.12
4 (0-269)
11 (0-117)
0.09
Days on hospice
Documented Resuscitation
11 (28)
18 (53)
0.05
Preference
105
deaths at time of data analysis with data on chemotherapy within 14 DOD available on 90 patients
Overall survival
Survival Analysis
Early palliative care
Median Survival
Early palliative care 11.6
mo
Standard care 8.9 mo
p=0.02
Standard care
Months
Controlling for age, gender and PS, adjusted HR=0.59 (0.40-0.88), p=0.01
Study Limitations
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Single, tertiary-care site with a specialized group
of clinicians.
Study population lacked racial/ethnic diversity.
Randomized design but no blinding to study
arm.
Small number of patients on standard care arm
seen by palliative care team.
Survival was not a pre-specified study endpoint.
Lack of information on mediators of patientreported and medical outcomes.
Summary
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Compared with standard oncology care,
integrated palliative care led to:
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Improvements in QOL
Lower rates of depression
Less aggressive care at the end-of-life
Greater documentation of resuscitation
preferences
Higher survival rates
Discussion
Changes in QOL may be due to improved
symptom management.
 Decreased rates of depression may be related to
improved symptom management and illness
acceptance.
 Prolonged survival possibly related to:
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Earlier recognition and management of medical issues
Improved QOL and mood
Less chemotherapy at the end-of-life
Longer hospice admissions
Acknowledgements
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Funding Provided by:
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William Pirl, MD, MPH
Joseph Greer, Ph.D
Inga Lennes MD
Emily Gallagher, BS
Sonal Admane, MBBS, MPH
Elyse Park, Ph.D
Areej El-Jawahri, MD
Center for Palliative Care at
Massachusetts General Hospital
Andrew J. Billings MD
Vicki Jackson MD
Connie Dahlin ANP
Craig Blinderman, MD
Juliet Jacobsen, MD
Amelia Cullinan, MD
Sandy Nasrallah, MD
Thoracic Oncology at
Massachusetts General Hospital
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Supportive Care Research Group
at Massachusetts General
Hospital
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ASCO Foundation
Golf Fights Cancer
The Joanne Hill Monahan Fund
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Panos Fidias, MD
Alice Shaw, MD, Ph.D
Rebecca Heist, MD
Lecia Sequist, MD
Jeff Engelman, MD, Ph.D
David Barbie, MD, Ph.D.
Inga Lennes, MD
Elizabeth Lamont, MD
Jeanne Vaughn, ANP
Diane Doyle, ANP
Patricia Ostler R.N
Thoracic Oncology research nurses,
administrators and staff
Yale Cancer Center
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Thomas J. Lynch, MD