Symptom control in patients with recurrent ovarian cancer Measuring the benefit of palliative chemotherapy in women with platinum refractory/ resistant ovarian cancer UPDATE

Study Schema REGISTERREGISTER 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 During Trial Stage1-100 Complete 7 QoL forms 20 subjects will be asked to participate in additional QoL telephone interview Stage Determine the optimal number of QoL forms from Stage1 Data Collection 4 Treatment cycles or Disease progression

Stage 1 identify and investigate The symptoms and aspects of HRQL that are rated as most severe, troublesome and important by patients. The improvements in scores for these aspects that occur with treatment. The optimal items and questionnaires for measuring these improvements. The criteria for defining a clinically significant improvement.

Stage 2 Primary Objective The proportion of women benefiting from palliative chemotherapy as defined by a clinically significant improvement in HRQL scores. 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/CA125 response. The effects of treatment, objective response and subjective response on scores for anxiety, depression and hope. Develop a prognostic index to predict benefit

QoL Instruments Symptom Representation Questionnaire SRQ FACT-O QLQ-C30 Ov-28( includes FOSI) Pt DATA Form Expected & perceived benefit HADS Herth Hope Index Patient identified major symptoms

Possible Symptoms Those that may improve- Abdominal distension- Ascites Abdominal pain- Intermittent SBO Pelvic symptoms- mass effect Anorexia- liver metastases Dyspnoea – pleural effusion

Makhija S et al. Proc ASCO 2007;Abstract PFS 3 m.

Makhija S et al. Proc ASCO 2007;Abstract 5507

Makhija S et al. Proc ASCO 2007;Abstract 5507

FOSI 8 items (subset of FACT-O), 1 scale

Prognostic Models 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 Psammoma bodies

Platinum Resistant Ovarian Cancer OS

Platinum Resistant Ovarian Cancer Hypothetical Risk Groups OS

Plans Continue accrual to stage 1- completed by end of year Seamless Transition through to stage 2 without stopping recruitment- drop questionnaires Potential for other groups to now prepare ethics and open across multiple sites Options- link to clinical trials in platinum resistant OC eg Aurelia, NOGGO etc as well non trial population in selected sites

Potential SIGNIFICANCE Development of better methods to assess and measure the clinical benefit of palliative chemotherapy Applicable to trials of palliative therapy in ovarian cancer as well has having broad clinical utility. Insight into how women with recurrent ovarian cancer are treated in different countries and among different member groups of the GCIG. Better understanding of the reasons why treatment is given, what proportion of women have symptoms related to disease, what their expectations of benefit are and what price they pay in terms of toxicity. Develop a prognostic index This information will influence clinical practice and help physicians and patients make informed decisions regarding treatment options.