Friday Poster Discussion. Heather Wakelee, MD Stanford University Stanford Cancer Institute

Transcription

1 Friday Poster Discussion Heather Wakelee, MD Stanford University Stanford Cancer Institute

2 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

3 Muscle wasting in cancer patients is a significant unmet medical need 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 Bruera E BMJ 315(7117): ; Prado CM, et al Clin Cancer Res 15(8):2920-6; Antoun S Ann Oncol Epub Ahead of Print; Ryan JL Oncologist 12(Suppl 1):22-34; Baracos VE Am J Clin Nutr 91(4):1133S-7S; Baracos VE. 2001; Cancer 92(6 Suppl): Modified from Dodson WCLC 2011

4 Phase IIb clinical trial in cancer patients with muscle wasting 16 week, randomized, double blind, placebo controlled trial 1 endpoint: total lean body mass (LBM) by dual energy x-ray absorptiometry (DXA) 2 nd endpoints: physical function as measured by stair climb power +time, QoL Additional analysis: OS assessed by >8% or 8% weight loss Dodson WCLC 2011

5 GTx-024 improved physical function Functional Assessment of Anorexia/Cachexia Therapy (FAACT) QoL measure correlated with physical function Dodson WCLC 2011

6 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)

7 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

8 Enobosarm physical function changes P=0.044 Eugonadal P=0.006 Hypogonadal

9 2 nd 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.

10 Enobosarm Adverse events

11 Physical Function by Wt Loss N = 39 (<5%); N = 119 (>5%) Baseline % change from baseline < 5% wt loss n=10(ns), N=15 p.002 >5% wt loss N= 27 NS; n=51 p<.001

12 Understanding Non-Small Cell Lung cancer from the Patient s Perspective: From disease defining symptoms to its impact on healthrelated quality of life By Susan Magasi, PhD 1, Rajiv Mallick, PhD 2, Beatriz Menendez, BA 1, David Cella, PhD 1 1 Northwestern University, 2Daiichi Sankyo Inc.

13 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.

14 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.

15 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.

16 Results: Most frequently reported symptoms

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

18 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.

19 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: 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

20 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

21 Introduction Stereotactic body radiation therapy (SBRT) offer excellent local control for small lung tumors However, many factors can affect patient setup and tumor localization

22 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

23 B Loo / Stanford 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)

24 B Loo / Stanford Thoracic SABR Conventional vs. SABR dose distribution

25 Y Nagata / JCOG 0403 / ASTRO 2010 SABR outcomes (n=64) 1.0 P r o b a b i l i t y Overall Survival Rate 3y (95% CI: 63.3% %) expected: 80%@3y Years Since Registration

26 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)

27 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

28 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%), cm (50%), 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%)

29 Results Pulmonary function 68 (76%) patients were past or current smokers, 59 (66%) with clinically significant COPD (13 oxygendependent) 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

30 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

31 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)

32 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

33 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