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