1 RTOG 1115 Health Related Quality of Life and Comparative Effectiveness Deborah Watkins Bruner, RN, PhD, FAAN

2 HRQoL Objectives To characterize differences between the treatment groups with respect to incidence of clinically significant decrement in patient reported quality of life (QoL) Changes in severity of fatigue Changes in patient reported QoL Assess quality adjusted survival Mandatory participation for the first 410 pts.

3 HRQoL Background Patient Reported Outcomes (PRO) is a key facet of the risk-benefit evaluation of prostate cancer High prevalence of fatigue in prostate cancer patients and its association with poor quality of life makes it a problem that merits further study

4 ADT Adverse Events In addition to hot flashes, sleep disturbances, erectile dysfunction, and osteoporosis: Standard ADT increases risk of insulin resistance and diabetes Insulin resistance is an independent risk factor for cardiovascular disease and is present in about one fourth of adults in the general population (Despres 1996, Pyorala 1998)

5 ADT Adverse Events Standard ADT has repeatedly been shown to cause weight gain Over one year, weight increased by 2.4% (+ 0.8%; P = 0.005), percentage fat body mass increased by 9.4% (+ 1.7%; P < 0.001), and percentage lean body mass decreased by 2.7% (+ 0.5%; P < 0.001). (Smith 2002) Similarly, a larger study of 79 men with nonmetastatic prostate cancer also showed significant weight gain (1.8% + 0.5%; P<0.001) during one year of ADT (Smith 2004).

6 TAK-700 Adverse Events Generally well tolerated when given in combination with a GnRH agonist Adverse events that have been observed to occur frequently include: – fatigue – nausea – constipation – anorexia – vomiting (Dreicer 2010)

7 HRQoL Assessments Related to Fatigue Patient Reported Outcome Measurement Information System (PROMIS)-Fatigue –Measures fatigue related symptoms, distress and effects on functioning Muscle Weakness Question –Scale of 1-5, from none to very much Pittsburgh Sleep Quality Index (PSQI) –Measures overall sleep quality (1 question) Godin Leisure-Time Exercise Questionnaire (GLTEQ) –Measures time spent each week performing light, moderate and vigorous activities

8 HRQoL Assessments Continued Expanded Prostate Cancer Index Composite (EPIC-26) –Measures urinary, bowel, sexual and hormonal symptoms related to hormonal and radiotherapy EuroQoL (EQ-5D) –Measures mobility, self care, usual activities, pain/discomfort and anxiety/depression

9 HRQoL Data Collection Time points Pre-treatment Week prior to RT start During the last week of RT 1 year (12 months) after therapy start 2.5 years (30 months) after therapy start

10 Comparative Effectiveness Patients with disease characteristics meeting the eligibility criteria for this study have: o 5-year survival of 78% o 8-year survival of 61.5%. We aim to detect a 33% reduction in failure rate for the experimental arm. This relative hazard reduction implies an absolute survival difference of 7% at five years. Question: Is the benefit of a 7% improval in survival worth the risk of additional side effects?

11 What You Can Do To Help Accrue! Understand the importance of the QOL component so you can help be an advocate in presenting the information to patients Be diligent about getting completed questionnaires on time BE FULLY INFORMED about patients who opt to discontinue filling out the forms does NOT mean they are withdrawing from the study!!