measuring the benefit of palliative chemotherapy in women with platinum refractory/ resistant...
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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?
● 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 !!
● Impact of treatment on HRQOL
● Which instruments do we use
● How important is hope in decision making?
● Would good palliative care achieve the same
● 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
Copyright © American Society of Clinical Oncology
Gordon, A. N. et al. J Clin Oncol; 19:3312-3322 2001
Median TTP- 9 vs. 13 w (NS)
Sobering reminder of the results of treatment
Kaplan-Meier curve of PFS ( platinum-resistant patients)
Response Rates 6.5% vs. 12.3% ( NS)
260 patients on study
Median Survival 35 w vs. 41 w ( NS)
Response Rates Symptom Control and QOL
● 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 cancer- a 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
0.00
0.25
0.50
0.75
1.00
0 10 20 30 40months
Chemotherapy, median time to progression: 87 daysTamoxifen, median time to progression: 62 days
HR: 0.72, 95% CI: 0.55 - 0.96, p=0.024
Progression free survivalProgression free survival
NSGO-OC-0101Kristenson G 2008
Overall Quality of life score EORTC QOL-C30 + OV28
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-0101Kristenson G 2008
Possible interpretation…
● '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. ProcASCO 2007;Abstract 5507
GCIG Symptom Control Study
HYPOTHESES
● 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
REGISTER
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 formsindependently
Stage1100 patients
• Complete 7 QoL forms• 20 subjects will participate in additional QoL telephone interview
Data Collection
4 Treatment
cycles or
Disease progression
Primary Objective● 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● 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.
● The most common and important symptoms as defined by the patients themselves.
● Whether these patient defined symptoms improve with chemotherapy● 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
STAGE 2 400 -500 patients
Hypothetical Risk Groups
Conclusions- with respect to study● General:
– QOL measures result in a lot of data and outcome variables to analyse & interpret– The relationship among them is complicated– Particularly so for the relationship between specific symptoms and overall QOL– Potential diluting effects with the more expansive/inclusive definitions & measures of
QOL– 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:– FOSI appears to have the right content & mix for a single index measure – Likely to sensitive to palliative benefits of therapy
AND to deterioration due to disease progression
● We will explore all these questions in depth in our study