, START UP MEETING FOR STAGE 2

Response Rates in Phase 3 Trials Chemotherapy Response rates % Liposomal doxorubicin Gemcitabine 5-9 Gemcitabine + Pertuzumab 13 Topotecan 6 Trabectedin 7 Patupilone 15 Patients with good PS entered into clinical trials- 2 nd Line Therapy

Symptom Benefit Study Expectation is that Symptom Benefit > Response Rate ( otherwise why would we treat so many patients ) How to best measure the impact of chemotherapy on symptom improvement ? Can we use Symptom Benefit Measures as an alternative outcome measure Can we identify patients most likely to benefit from palliative chemotherapy?

Stage 1-Primary Aim The symptoms and aspects of HRQL that are rated as most severe, troublesome and important by patients. The optimal items and questionnaire/s for measuring these improvements.

REGISTERREGISTER REGISTERREGISTER Target Population >18yrs platinum resistant/ refractory epithelial ovarian cancer /> 3 lines of therapy ECOG 0-3 Able to commence treatment within 2wks of registration Sufficient English to complete QoL forms independently Target Population >18yrs platinum resistant/ refractory epithelial ovarian cancer /> 3 lines of therapy ECOG 0-3 Able to commence treatment within 2wks of registration Sufficient English to complete QoL forms independently Stage1 100 patients Complete 7 QoL forms 20 subjects will participate in additional QoL telephone interview Stage1 100 patients Complete 7 QoL forms 20 subjects will participate in additional QoL telephone interview Data Collection 4 Treatment cycles or Disease progression Data Collection 4 Treatment cycles or Disease progression Study Schema

Stage 1 QoL Questionnaires Symptom Representation Questionnaire FACT-O (includes FOSI) EORTC QLQ-C30 EORTC QLQ-OV28 Patient Data Form Expected and Perceived Benefit Scale HAD Scale (Baseline & End of Treatment) Herth Hope Index (Baseline & End of Treatment only)

Results Majority Platinum Resistant Compliance 96% All questionnaires were completed to a very high compliance rate with few or no missing data

Reasons for Starting Chemotherapy REASONS FOR CHEMOTHERAPYPatients (N=89) Symptom control only 1 Rising CA125 only 1 Radiological evidence only 1 Symptom control + rising CA125 only 15 Symptom control + radiological evidence only 4 Rising CA125 + radiological evidence only 19 Symptom control + rising CA125 + radiological evidence 48

Patients “3 most noticed symptoms” and clinician rated AE’s at baseline CAUSESYMPTOM % Patients reported (N=83) % AE reported by clinician (N=92) BOTH TREATMENT & DISEASE FATIGUE40%55% PREDOMINANTLY DISEASE RELATED PAIN (ABDOMINAL/ UNSPECIFIED)40%32% ABDOMINAL PROB/BLOATING30%17% NAUSEA/VOMITING20%33% BOWEL PROBLEMS20%27% SHORTNESS OF BREATH12%2% APPETITE LOSS11% (Anorexia 22%) PREDOMINANTLY EMOTIONAL SLEEP DISTURBANCE27%4% DEPRESSION/MOOD PROBLEMS12%5%

Number of Lines of Prior Therapy Previous Lines Patients UK5

Improvement in quality of life (Prior to Cycle 3 N=72) Is your symptom improvement enough to affect your overall quality of life?

Stage 1-outcome Results have led to development of MOST (Measure of Ovarian cancer Symptoms and Treatment concerns ) Modification of Patient Data Form COVERS ALL SYMPTOMS AND ASPECTS OF QOL IDENTIFIED IN STAGE 1

MOST Measure of Ovarian cancer Symptoms and Treatment concerns Comprises of 35 individual items on a discrete scale of 0-10, where major symptomatic distress is represented by 10. The first 15 items refer to disease symptoms Items 16 and 17 refer to physical and emotional well-being Item 18 is a question referring to overall well-being Items deals with side effects and other concerns The study will examine the extent of clinical improvement by examining changes in these items from baseline at each time point - to determine MCID

Schema – Stage 2 REGISTERREGISTER REGISTERREGISTER Data Collection Baseline Each treatment cycle One month post completion of treatment or until disease progression Data Collection Baseline Each treatment cycle One month post completion of treatment or until disease progression Target Population Informed consent ≥18yrs Platinum Resistant/Refractory ECOG 0-3 Life expectancy > 3 months Able to commence treatment within 2wks of registration Able to complete questionnaires independently Target Population Informed consent ≥18yrs Platinum Resistant/Refractory ECOG 0-3 Life expectancy > 3 months Able to commence treatment within 2wks of registration Able to complete questionnaires independently

Stage 2 Primary Objective To determine: The criteria for defining a clinically significant subjective improvement and the optimal instrument/s to measure benefit Secondary Objectives The proportion of women benefiting from palliative chemotherapy The time to symptom deterioration The proportion of women who receive treatment because they are (a) symptomatic, (b) have rising tumor markers alone, or (c) have imaging evidence of disease progression The percentage of patients who complete 4 or more cycles of treatment The most common, most severe and most noticed symptoms as perceived by patients. Develop a prognostic index

Stage 2 MOST FACT-O EORTC QLQ C30 EORTC OV28 Expected and Perceived Benefits These forms will be completed at Baseline and after each cycle until chemotherapy ceases.

Prognostic Factors

Recruitment The recruitment target is 600 evaluable patients (~780 enrolled patients) The estimated recruitment period is until December 2011 Currently there are 20 sites activated and 101 patients recruited with a further 40+ sites to open International participation Canada (additional sites) To be confirmed United Kingdom Japan Ireland Spain Germany Scandinavia Italy France USA- selected sites

Study Chair:Professor Michael Friedlander ANZGOG Coordinating Centre: Symptom Benefit NHMRC Clinical Trials Centre Locked Bag 77 CAMPERDOWN NSW 1450 AUSTRALIA Study Central Coordinator: Kim Gillies Data Manager: Lisa Martyn Program Manager: Julie Martyn Central Study Contacts