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

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.

QLM 0301ENROLL IN STUDY

•After progressing through 1 or more second line platinum resistant chemotherapy agents

Enrollment, and 6 months

FACT-O, -F, +2 Questions = FOSI-Abd Dis, NEST,

Performance StatusWeightResponse rate or tumor status

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

Primary, Neoadjuvant, and Adjuvant Chemotherapy in Elderly Women with Ovarian , Peritoneal

Primary or Tubal Cancer

Vivian von Gruenigen MD, Arti Hurria MDMerrill Egorin PhD, Mark Brady PhD, Tom Herzog MD,

Elisa Eldermire RN

OVM0502

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

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

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

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.”

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

Questions

• 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?

Lunney, J. R. et al. JAMA 2003von Gruenigen et al. Cancer 2008

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

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.

Interval surgery (if no primary surgery), and/or further chemotherapy at discretion of the physician

GOG 218, -R(primary surgery

only)

Carboplatin AUC 5 every 3 weeks X 4

Carboplatin AUC 5Paclitaxel 135 mg/m2

Plus G-CSFevery 3 weeks X 4Clinical Stage III-IV

confirmed and elevated CA125 > 50 at age > 75, PS 0-3. Investigator decides primary surgery vs. chemotherapy and adj chemotherapy

PROTOCOL OVM0502

PROs @baseline, prior to Cycle 3, 3-6 weeks after Cycle 4, and 6 months after completion of chemotherapy

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.

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.

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.