Measuring the benefit of palliative chemotherapy in women
with platinum refractory/ resistant ovarian cancer
Michael Friedlander Phyllis Butow, Martin
Stockler, Corona Gainford, Julie Martyn, Amit
Oza, Heidi Donovan, Brigitte Miller and
Madeline King
Chemotherapy in platinum resistant/refractory ovarian cancer
What do we know and What don’t we know?
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Goal- palliation and symptom control
Objective response rates are low
Benefits as well as adverse side effects of
treatment
How to best measure benefit
How does objective response correlate with
symptom benefit
What % are symptomatic at the time of treatment
Do these symptoms improve
But ….still many Questions !!
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Impact of treatment on HRQOL
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Which instruments do we use
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How important is hope in decision making?
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Would good palliative care achieve the same
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How much time do patients spend in hospital as a result
of toxicity
How many patients receive treatment within 30 days of
death
Can we identify patients most likely to benefit
Platinum Resistant Ovarian Cancer
• Patients on clinical trial not necessarily
representative of the population as a
whole
• Better Performance Status/younger etc
• Objective response rates generally low -in
order of 10-15%
• Not clear whether symptoms improve and
what price they pay for treatment
Kaplan-Meier curve of PFS ( platinum-resistant patients)
Response Rates 6.5% vs. 12.3% ( NS)
Median TTP- 9 vs. 13 w (NS)
Median Survival 35 w vs. 41 w ( NS)
260 patients on study
Gordon, A. N. et al. J Clin Oncol; 19:3312-3322 2001
Sobering reminder of the results of treatment
Copyright © American Society of Clinical Oncology
Response Rates Symptom Control and QOL
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Response rates crude way to measure benefit
Doyle et al reported improved QOL and
emotional well being in 50-60% of patients
receiving 2nd line treatment while ORR was
25%
Large study using EORTC QLQ-C-30 in 500
women with recurrent ovarian cancer reported no
change in QOL during treatment- i.e. no change
from baseline, after 3 cycles and at completion of
therapy
Chemotherapy versus hormonal treatment in patients
with platinum and taxane resistant ovarian cancera NSGO study (NSGO-OC-0101)
On behalf of NSGO
G. B. Kristensen, J. Kaern, E. Åvall-Lundqvist, R.
dePont Christensen, S. Grenman, M. Bergdahl, R.
Sandvei, M. Baekelandt, T. Skeie-Jensen,M.
Kalling, T. Hoegberg,
Presented IGCS Bangkok 2008
1.00
Progression free survival
0.75
Chemotherapy, median time to progression: 87 days
Tamoxifen, median time to progression:
62 days
0.00
0.25
0.50
HR: 0.72, 95% CI: 0.55 - 0.96, p=0.024
0
10
20
months
30
NSGO-OC-0101
40
Overall Quality of life score
EORTC QOL-C30 + OV28
Basis
Mean
Max
Tamoxifen
48.6
46.1
54.9
W-paclitaxel
54.8
48.7
56.6
Peg. Doxo
49.3
45.2
57.0
No significant differences between
treatment groups
NSGO-OC-0101
Kristenson G 2008
Possible interpretation…
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'Global QOL scale may not be sensitive enough to
pick up differences'
There must be better ways to measure symptom
control and palliative benefit
FOSI 8 items (subset of FACT-O), 1 scale
Makhija S et al. Proc
ASCO 2007;Abstract 5507
GCIG Symptom Control Study
HYPOTHESES
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The subjective improvement of palliative chemotherapy
and clinical benefit will be significantly greater than
objective response rates.
Clinical benefit measures that incorporate both
objective response and subjective improvement will
provide a more meaningful method of evaluating the
effect of palliative chemotherapy
It should be possible to identify which patients are more
likely to benefit from palliative chemotherapy as well as
the group who have little benefit i.e develop a
prognostic index/score
Study Schema
Target Population
>18yrs
platinum resistant/
refractory epithelial
ovarian cancer
/ > 3 LINES
ECOG 0-3
Able to commence
treatment within 2wks
of registration
Sufficient English
language skills to
complete QoL forms
independently
R
E
G
I
S
T
E
R
Stage1
100 patients
• Complete 7 QoL
forms
• 20 subjects will
participate in
additional QoL
telephone interview
Data
Collection
4 Treatment
cycles
or
Disease
progression
STAGE 2 400 -500 patients
Primary Objective
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To determine the proportion of women benefiting from palliative chemotherapy as
defined by a clinically significant improvement in HRQL scores and symptom
benefit as well as objective response.
Develop a better measure of symptom benefit for clinical trials
Secondary Objectives
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The proportion of women who receive treatment because they are (a)
symptomatic, (b) have rising tumor markers alone, and or (c) have imaging
evidence of disease progression alone.
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The most common and important symptoms as defined by the patients themselves.
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Whether these patient defined symptoms improve with chemotherapy
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Whether improvements in symptoms and HRQL correlate with objective
response.
The effects of treatment, objective response and subjective response on scores for
anxiety, depression and hope.
Derive a prognostic index to better predict outcomes and likelihood of benefit
Hypothetical Risk Groups
Conclusions- with respect to study
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General:
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QOL measures result in a lot of data and outcome variables to analyse & interpret
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The relationship among them is complicated
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Particularly so for the relationship between specific symptoms and overall QOL
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Potential diluting effects with the more expansive/inclusive definitions & measures of
QOL
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Important to focus on the symptoms that really matter to patients in a particular
context and whether they improve
In the context of palliative chemo for platinum refractory/resistant ovarian
cancer:
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FOSI appears to have the right content & mix for a single index measure
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Likely to sensitive to palliative benefits of therapy
AND to deterioration due to disease progression
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We will explore all these questions in depth in our study