QLM0301 Quality of life and Care Needs in Advanced Ovarian Cancer Patients

1. QLM0301Quality of life and Care Needs in Advanced Ovarian Cancer Patients Vivian von Gruenigen MD, Lari Wenzel, PhD David Cella PhD, Nancy Fusco RN Helen Huang MS

2. QLM 0301 Objectives To identify symptoms and needs which disrupt quality of life (QOL) in patients with platinum resistant ovarian cancer from study entry to 6 months post enrollment • Cumulative incidence of symptoms (FOSI) which coincide with ↓ QOL (FACT-O, -F, -Abd Dis) and clinical measures (PS, disease status, weight change) • To identify unmet needs as measured by the “NEST” instrument • To examine the relationship between symptoms, QOL, clinical disease and treatment data.

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4. Needs at the End-of-Life Screening Tool (NEST) • 13 items which assess 4 clusters of human need at the end of life: • Needs (social), • Existential, • Symptoms, • Therapeutic • study entry – baseline measurement • 6 months Emanuel LL et al. J Palliat Med 2001

5. Primary, Neoadjuvant, and Adjuvant Chemotherapy in Elderly Women with Ovarian , Peritoneal Primary or Tubal Cancer OVM0502 Vivian von Gruenigen MD, Arti Hurria MD Merrill Egorin PhD, Mark Brady PhD, Tom Herzog MD, Elisa Eldermire RN

6. Background • US population aging • The current population of elderly will more than double within the next thirty years. • Cancer incidence rises with age • 2/3 of solid tumors occur in patients 65+ • Cognitive disability and frailty are rapidly becoming dominant elements in old age. • Lynn J. Sick to Death 2004 • Smith BD, Hurria A. et al JClinOncol 2009

7. Background • Co-morbidity - Overall more important than chronological age • Needs to be assessed independent from functional status • Most elderly are living with more than one chronic condition • Goodwin JS et al. Cancer 1993 • Extermann M et al. J Clin Oncol 1998

8. Background • Accrual rates to trials for elderly ovarian cancer patients are lower compared to pancreatic, colon, lung, leukemia and breast cancers • Practitioners’ “attitudes” should be monitored to assure that elderly patients are not inappropriately denied participation on GOG trials • Talarico L et al ASCO 2003 • Moore DH et al. Gynecol Oncol 2004

9. GOG/SDC/DMCMemorandum 2003 GOG-0182 • The overall death rate within the first 6 months of entering the study • for patients ≥ 80 was 30% • For patients ≥ 70-79 was 7% GOG-158 and ICON3 • The overall death rate within the first 6 months of entering • for patients ≥ 80 was 33% • For ICON3 it was “somewhat higher.”

10. Side Effects • Elderly are less likely to receive surgery, and/or combination chemotherapy • Have a higher proportion of post-operative complications, reductions of chemotherapy cycles/doses and post-operative deaths. • Bone marrow suppression, nausea and vomiting are more common and severe • Dose-reduced regimens: T-175, Carbo-AUC 5/6 vs Taxol- 135, Carbo-AUC 4/5) • Fewer side effects including bone marrow suppression, delays, neutropenic fever and hospitalizations • No survival differences Wenzel L et al. J Clin Oncol 2005; Moore KN et al. Gynecol Oncol 2008, Fader A, von Gruenigen, Gynecol Oncol, 2008; Uyar D, von Gruengien, Gynecol Oncol 2005

11. Questions Lunney, J. R. et al. JAMA 2003 von Gruenigen et al. Cancer 2008 What is the QOL of elderly ovarian cancer patients? What type of impact does their “age” have on QOL and feasibility of surgery/chemotherapy? Why is the elderly cancer death rate so high (GOG 182, 158; ICON3)? And, what are the causes of death? What is their trajectory of decline and what happens to QOL and needs? What doses should we give? PK differences? What about >80 years? PFS, OS differences?

12. Geriatric Measures • Activities of daily living (ADL) • Instrumental activities of daily living (IADL) • Nutritional status (BMI, % unintentional weight loss) • Co-morbidity (Charlson Index) • PS • Extermann M, Hurria A. J Clin Oncol 2007

13. Design • IADL to predict tolerability of chemotherapy for elderly (age > 75) • Initially, the investigator decides between primary surgery versus primary chemotherapy • The physician also chooses between different chemotherapy regimens versus placing the patient on GOG 218-R. • Treatment after the four cycles of chemotherapy is at the discretion of the treating physician.

14. Carboplatin AUC 5 Paclitaxel 135 mg/m2 Plus G-CSF every 3 weeks X 4 Clinical Stage III-IV confirmed and elevated CA125 > 50 at age > 75, PS 0-3. Investigator decides primary surgery vs. chemotherapy and adj chemotherapy Interval surgery (if no primary surgery), and/or further chemotherapy at discretion of the physician Carboplatin AUC 5 every 3 weeks X 4 GOG 218, -R (primary surgery only) PROTOCOL OVM0502 PROs @baseline, prior to Cycle 3, 3-6 weeks after Cycle 4, and 6 months after completion of chemotherapy

15. Objectives • To assess % of patients who are able to complete 4 cycles (reductions/delays) • To determine whether baseline IADL predicts patients who are able to complete 4 cycles of chemotherapy (reductions/delays) • To compare actual and calculated (using standard GOG Jeliffe formula) carboplatin AUC in this patient population.

16. Secondary Objectives • Assess % treated with primary surgery versus primary chemotherapy • Treatment regimen choice • IADL at baseline predicts physician choice of primary surgery, primary chemotherapy and/or interval surgical cytoreduction • IADL at baseline predicts physician choice of chemotherapy regimen • Relationship between IADL at baseline and morbidity in patients receiving primary surgery.

17. Secondary Objectives • Relationship of age, geriatric measures (ADL, PS, FACT, nutritional status, co-morbidity) correlation with completion of 4 cycles of chemotherapy • Reasons and timing of dose reductions and delays • Toxicities, serial QOL, and relationships with geriatric measures. • Explore whether patients with CR return to their pre-treatment scores of QOL and geriatric assessment following completion of therapy. • Describe RR, OS, PFS on each arm of therapy Translational Research Objective • To explore relationships between carboplatin AUC, paclitaxel, and paclitaxel time above a plasma concentration of 0.05 mM with nadir neutrophil and platelet counts during Cycle 1 of treatment.