Friday Poster Discussion

Heather Wakelee, MD

Stanford University

Stanford Cancer Institute

Posters

• DR. STEINER- PREVALENCE AND IMPACT OF

HYPOGONADISM IN CANCER PATIENTS WITH MUSCLE

WASTING IN A PHASE IIB ENOBOSARM TRIAL

• DR. STEINER- EFFECT OF ENOBOSARM ON PHYSICAL

FUNCTION IN CANCER PATIENTS WITH < OR ≥5% WEIGHT

LOSS IN A PHASE IIB TRIAL

• DR. MAGASI- UNDERSTANDING NON-SMALL CELL LUNG

CANCER FROM THE PATIENT'S PERSPECTIVE: FROM

DISEASE DEFINING SYMPTOMS TO ITS IMPACT ON QUALITY

OF LIFE

• DR. SIO- IMPACT OF PULMONARY FUNCTION AND BODY

HABITUS ON PATIENT IMMOBILIZATION FOR UPPER LUNG

TUMORS USING STEREOTACTIC BODY RADIOTHERAPY

50% of patients with cancer have muscle wasting

Loss of skeletal muscle and physical decline

GTX-024 (Enobosarm) selective androgen receptor modulator

Potential to reduce muscle wasting

Used lean body mass and stair climb power as measurement of efficacy

Randomized 159 pts to oral drug versus placebo (61 w/ NSCLC)

Previously reported on the stair climb power (WCLC 2011)

Posters today with data on :

Hypogonadism

Physical Function w/wo 5% weight loss

Muscle wasting in cancer patients is a

significant unmet medical need

Bruera E. 1997. BMJ 315(7117):1219-22; Prado CM, et al. 2009. Clin Cancer Res 15(8):2920-6; Antoun S. 2010. Ann Oncol Epub

Ahead of Print; Ryan JL. 2007. Oncologist 12(Suppl 1):22-34; Baracos VE. 2010. Am J Clin Nutr 91(4):1133S-7S; Baracos VE.

2001; Cancer 92(6 Suppl):1669-77.

Modified from Dodson WCLC 2011

Phase IIb clinical trial in cancer patients with muscle wasting

16 week, randomized, double blind, placebo controlled trial

Dodson WCLC 2011

• 1 endpoint: total lean body mass (LBM) by dual energy x-ray absorptiometry (DXA)

• 2nd endpoints: physical function as measured by stair climb power +time, QoL

• Additional analysis: OS assessed by >8% or ≤8% weight loss

GTx-024 improved physical function

Functional Assessment of Anorexia/Cachexia Therapy (FAACT) QoL measure

correlated with physical function

Dodson WCLC 2011

Hypogonadism poster

• Hypogonadism is associated with weight loss and poor

outcomes in cancer patients

• Up to 50% of men w/ adv cancer are hypogonadal

• Pts (n=159; 61 NSCLC) were randomized to

enobosarm or placebo for 16 weeks

• Report on incidence and impact of hypogonadism

(T<300 ng/dL)

Hypogonadism poster

• Baseline testosterone levels were available for 93/103 men

• 60% of males were hypogonadal at randomization

• Distribution of hypogonadism was similar across cancers

• Hypogonadal men were less likely to complete the study

• Baseline T was correlated with weight loss (r=0.32, P=0.002)

– hypogonadal men had greater loss in previous six months (median, -9.5%).

• Baseline physical function (stair climb power) was higher among

eugonadal versus hypogonadal males

– 174 watts vs 147 watts; P=0.02

• Enobosarm significantly improved physical function regardless of

baseline gonadal status

– eugonadal:12%, P=0.044; hypogonadal:17%, P=0.006

Enobosarm physical function changes

•

P=0.044 P=0.006

Hypogonadal Eugonadal

2nd Enobosarm poster

• 103 evaluable subjects had physical function (stair climb) assessed

at baseline and week 16

• 24% had lost <5% weight in previous 6 months

• Distribution of weight loss was similar across genders

• Subjects with <5% weight loss were more likely ECOG=0

• Subjects with ≥5% weight loss had worse physical function at

baseline compared to those with <5% loss.

• Significant improvement in physical function was observed in

enobosarm subjects regardless of baseline weight loss (<5%,

P=0.002, ≥5%, P<0.001) while placebo subjects failed to improve.

Enobosarm Adverse events

•

Physical Function by Wt Loss

• Baseline

% change from baseline

N = 39 (<5%); N = 119 (>5%)

< 5% wt loss

n=10(NS), N=15 p.002

>5% wt loss

N= 27 NS; n=51 p<.001

Understanding Non-Small Cell Lung cancer from the Patient’s Perspective: From disease defining symptoms to its impact on health-

related quality of life

By

Susan Magasi, PhD1, Rajiv Mallick, PhD2, Beatriz Menendez, BA1, David Cella,

PhD1

1 Northwestern University, 2Daiichi Sankyo Inc.

Background

• Among patients with advanced (NSCLC), reducing or delaying deterioration of symptoms can be a meaningful treatment outcome.

• As new cancer therapies are developed, it is important to evaluate their clinical benefit based not only on survival outcomes but also on the symptoms and concerns important and relevant to patients.

• Prior to assessing treatment benefit in terms of patient-reported outcome scales in clinical trials in NSCLC, it is important to document that the scales reflect key symptoms experienced by people with NSCLC.

• The purpose of this study was to characterize pulmonary symptoms among patients receiving first line treatment for advanced NSCLC.

Methods

Semi-Structured Interviews

• Patient interviews involved open-elicitation and direct probing about NSCLC symptoms and experiences.

Content Analysis

• Descriptive coding of verbatim transcripts in Atlas-ti was undertaken.

• Excerpts were assigned sub-codes representing symptom impacts experiences and later collapsed into broad symptom codes.

Results

• Participants described a broad range of issues related to their lung cancer, including symptom experiences (both disease-defining and generalized), treatment attributed effects, and functional and emotional impacts of the disease.

• 32% of the participants (8/25) indicated that either they had no pulmonary symptoms or that their pulmonary symptoms had abated since treatment.

Results: Most frequently reported symptoms

Results – Conceptual model of patient reported impact of NSCLC and its treatment

Conclusions

• Given the reported diversity of symptoms from disease defining symptoms like cough and shortness of breath to distal impacts like emotional tolls, a global symptom index such as the NCCN-FACT, FACT-L, or EORTC-QLQ-LC-13 can provide comprehensive content coverage of the most key symptoms.

• Our conceptual measurement model distinguished disease related symptoms, proximal disease impacts, treatment effects, and distal impacts on health-related quality of life, and can enable practitioners and regulators to monitor therapeutic interventions (e.g. pharmacological and psychosocial) with greater specificity.

Prevalence of Symptoms in Adv Cancer Walsh et al. The symptoms of advanced cancer: relationship to age, gender and performance status in 1000

patients. Support Care Cancer (2000) 8: 175-179

Symptom % Symptom %

Pain 84% Depression 41%

Fatigue 69% Cough 38%

Weakness 66% Nausea 36%

Anorexia 66% Edema 28%

Xerostomia 57% Taste Change 28%

Constipation 52% Hoarseness 24%

Early Satiety 51% Anxiety 24%

Dyspnea 50% Vomiting 23%

Weight loss 50% Confusion 21%

Sleep problems 49%

Slide courtesy Kavitha Ramchandran

Impact of Pulmonary Function and Body Habitus on Patient Immobilization for Upper

Lung Tumors Using Stereotactic Body Radiotherapy (SBRT)

Sio TT, Brown LC, Blanchard MJ, Jensen

AR, Ma DJ, Fong de los Santos LE, Park

SS, Olivier KR Department of Radiation Oncology, Rochester, MN

Introduction

• Stereotactic body radiation therapy

(SBRT) offer excellent local control for

small lung tumors

• However, many factors can affect patient

setup and tumor localization

Objectives

• To evaluate the influence of patient’s

pulmonary function and body habitus on

setup and reproducibility for upper lung

tumors as treated by SBRT

What is Stereotactic Ablative Radiotherapy (SABR)?

• Highly focused radiation concentrated on small

tumors – low dose to surrounding tissue

• Highly dose intensive – Single or few treatments,

high biologically effective dose

• Highly accurate & precise delivery – image

guidance, immobilization, and other technologies

to ensure accuracy

• AKA: SBRT, SRT, radiosurgery (SRS),

extracranial stereotactic radioablation (ESR)

B Loo / Stanford

Thoracic SABR

Conventional vs. SABR dose distribution

B Loo / Stanford

SABR outcomes (n=64)

0.0

0.2

0.4

0.6

0.8

1.0

0 1 2 3 4 5

Years Since Registration

P

r

o

b

a

b

i

l

i

t

y

76.0% @ 3y (95% CI: 63.3% - 84.8%) expected: 80%@3y

Overall Survival Rate

Y Nagata / JCOG 0403 / ASTRO 2010

Methods

• April 2008 to November 2011

• Prospective SBRT database (Mayo Clinic)

• 89 patients receiving SBRT to upper lung

• Two immobilization techniques: BodyFIX (left), and

S-frame with shoulders (right)

Methods (continued)

• Shifts from initial couch measured by serial

cone-beam CT (CBCT) analyzed

• Institutional tolerance of 3-D CBCT-based

shifts for treatment was 2, 2, 4 mm; shifts

exceeding these limits needed re-imaging

• Calculated Couch shifts, compared as square

root of sum of squares in x, y, z-directions,

• Gating or breathing control was not employed

Results – Patient characteristics

• Median f/u: 8.7 months

• Median age: 71.8 years

• 64 NSCLC, 29 metastatic tumors

• Lesion sizes were: <1 cm (15%), 1.1-2 cm

(50%), 2.1-3 cm (25%), and >3 cm (10%)

• 21 central and 72 peripheral tumors

• Dose schemes: 4800/4 (cGy/fraction, 28%), 5000/5

(24%) and 5400/3 (46%)

Results – Pulmonary function

• 68 (76%) patients were past or current smokers, 59

(66%) with clinically significant COPD (13 oxygen-

dependent)

• Larger total lung capacity (TLC, suggesting air trapping

in COPD patients) was related to larger setup

difference in first couch shifts (p<0.040)

• Larger TLC (p<0.0001) and residual volume (RV,

p<0.0039) were correlated with increased number of

required couch shifts per SBRT fraction, independent of

immobilization choice

Results – Body habitus

• 28 (31%) patients were obese (BMI>30)

• Increased patient weight was related to

more setup uncertainty

• Increased body mass index were directly

related to larger averaged couch shift

errors by CBCT

Results – Local control

• For all pts, 2 and 3-yr local control (LC)

rates were 94% and 81%, respectively

• There is no difference in LC by patient’s

age, PFT function, body habitus, COPD

or smoking status, though tumors larger

than 2cm had poorer LC in the final

multivariate analysis (Log-rank p<0.0058)

Conclusions

• Patients with obese habitus and

advanced emphysema experienced more

SBRT setup uncertainty by CBCT

• However, their outcome and probability

for local tumor control remained excellent

when compared to their counterparts in

the same cohort

Posters Conclusions

• HYPOGONADISM IS COMMON AND IS LINKED TO WEIGHT

LOSS AND MUSCLE WASTING

• ENOBOSARM SHOWS PROMISE FOR OVERCOMING MUSCLE

WASTING IN PATIENTS REGARDLESS OF PRIOR WT LOSS

• BETTER TOOLS IN DEVELOPMENT TO ASSESS PATIENT

SYMPTOMS

• SBRT CAN BE GIVEN SAFELY AND EFFECTIVELY TO OBESE

PATIENTS AND THOSE WITH COPD