1. NHMRC Clinical Trials Centre ANZGOG AGM, 2 April 2009, Noosa NHMRC Clinical Trials Centre Symptom Benefit Study Measuring the Benefit of Palliative Chemotherapy in women with platinum refractory/ resistant ovarian cancer ANZGOG – 0701

2. NHMRC Clinical Trials Centre ANZGOG AGM, 2 April 2009, Noosa NHMRC Clinical Trials Centre Study Background The aim is to develop a method to measure the benefit of chemotherapy, which takes into account BOTH subjective and objective responses Document time to symptom progression as an additional endpoint as well as symptom benefit Better insight into patterns of care and reasons for treatment with platinum resistant or refractory ovarian cancer Develop a prognostic index that better defines outcomes and test in a separate group

3. NHMRC Clinical Trials Centre ANZGOG AGM, 2 April 2009, Noosa NHMRC Clinical Trials Centre Objective Stage 1: To determine the symptoms and aspects of HRQL that are rated most severe, troublesome in patients and identify best instruments to use in stage 2 Stage 2: To determine the proportion of women benefiting from palliative chemotherapy as defined by a clinically significant improvement in HRQL scores and improvement of symptoms and time to symptom progression.

4. NHMRC Clinical Trials Centre ANZGOG AGM, 2 April 2009, Noosa NHMRC Clinical Trials Centre REGISTERREGISTER Target Population >18yrs platinum resistant/ refractory epithelial ovarian cancer ECOG 0-3 Able to commence treatment within 2wks of registration Ability to complete QoL forms independently During Trial Stage1 Complete QoL questionnaires at each cycle 20 subjects will participate in additional QoL telephone interviews Stage2 Determine the optimal QoL forms from Stage1 Longer follow-up Prognostic data collected at baseline Data Collection 4 Treatment cycles or Disease progression Proposed longer follow-up for Stage 2 Study Schema

5. ANZGOG AGM, Noosa 2 April 2009 NHMRC Clinical Trials Centre Current status Fourteen sites open to recruitment Twelve in Australia Two in Canada A further nine Australian sites are currently awaiting final ethics approval Total recruitment 46 26 Australia 20 Canada

6. ANZGOG AGM, Noosa 2 April 2009 NHMRC Clinical Trials Centre Baseline Demographics Symptom control/palliation + rising CA125 + radiological progression28 Rising CA125 + radiological progression9 Symptom control/palliation + rising CA1256 Symptom Control + radiological evidence1 Radiological Evidence only1 Rising CA125 only1 N = 46 Reason for treatment at enrolment

7. ANZGOG AGM, Noosa 2 April 2009 NHMRC Clinical Trials Centre Baseline Demographics cont’d Major symptoms reported at baseline: 1. Pain 2. Fatigue 3. Abdominal Bloating ECOG 0 = 17 (N = 45 - missing data for one patient) 1 = 26 2 = 2 3 = 0

8. ANZGOG AGM, Noosa 2 April 2009 NHMRC Clinical Trials Centre Stage 1 QoL Questionnaires 1.Symptom Representation Questionnaire 2.FACT-O (includes FOSI) 3.EORTC QLQ-C30 4.EORTC QLQ-OV28 5.Patient Data Form 6.Expected and Perceived Benefit Scale 7.HAD Scale (Baseline & End of Treatment only) 8.Herth Hope Index (Baseline & End of Treatment only)

9. ANZGOG AGM, Noosa 2 April 2009 NHMRC Clinical Trials Centre Results: Top 10 Symptoms of the ‘Three Most Noticed Symptoms in the last week’ at baseline RankSymptom No. who nominated this symptom in her Top 3 (n=31) 1Fatigue17 2Pain - general11 3Abdominal bloating10 4Sleep disturbance9 5Nausea and vomiting8 6Appetite7 7Shortness of breath6 8Bowel disturbances (including constipation)6 9Pain - abdominal5 10Urinary problems3

10. ANZGOG AGM, Noosa 2 April 2009 NHMRC Clinical Trials Centre Coverage of Top 10 symptoms by candidate questionnaires Symptom SRQPt DATAFACT-OFOSIQLQ-C30QLQ-OV28 Fatigue21 113 - Pain - general 11112- Abdominal bloating1111-1 Sleep disturbance111-1- Nausea and vomiting22222- Appetite121-11 Shortness of breath11--1- Bowel disturbances131-23 Pain - abdominal-111-1 Urinary problems11---1 # items covering Top 10121596129 Total # items in q’aire24183983028 %50%83%23%75%40%32%

11. ANZGOG AGM, Noosa 2 April 2009 NHMRC Clinical Trials Centre Decisions Retain modified Pt DATA Form – Ovarian to measure key symptoms Enhance coverage of the Top 10 Allow measurement of both current status and change Modifications by developer and OSBS investigators  OSBS Recent Status Form (after each cycle) OSBS Change Form(after every 2 nd cycle) Develop a separate Side Effects Form for net clinical benefit Retain FACT-O (including FOSI) to measure QOL FACT-O Has fewer items: 39 (incl. 8 for FOSI) vs. 58 in the QLQ- C30/Ov28 Provides summary scores: overall QOL, Trial Outcome Index, FOSI Overall QOL based on all items QLQ-C30 22 sub scales Duplication of single-item symptoms with Pt DATA Form Global QOL based on 2 items

13. ANZGOG AGM, Noosa 2 April 2009 NHMRC Clinical Trials Centre Prognostic Model variables No. of lines of therapy Performance status Volume of disease Sites of disease CA125 velocity LDH; Hb; Albumin; Platelets Inflammatory markers Grade; histological subtype

14. ANZGOG AGM, Noosa 2 April 2009 NHMRC Clinical Trials Centre Platinum Resistant Ovarian Cancer Hypothetical Risk Groups PFS