Anatomic and Functional Imaging Evaluation of a Clinical Trial of an IGFR Antibody in Patients (PTS) with Ewing Sarcoma (ES) Vadim Koshkin; Vanessa Bolejack; Denise Reinke; Rashmi Chugh; Lawrence Schwartz; Shreyaskumar Patel; Lee Helman; Laurence Baker; Scott Schuetze Disclosure: Marathon, Morphotek, Cytrx Inc

Response and Progression in Solid Tumor Oncology ResponseProgression Assessed early in treatment course Assessed at intervals until change of therapy Not normally used to determine whether to change therapy Commonly used to determine when to change therapy Primarily used to calculate overall response rate Primarily used to calculate time to progression endpoints Timing of Assessment: Role in clinical Practice: Role in clinical Research: J Natl Cancer Inst.J Natl Cancer Inst Oct 17;104(20):

The Evolution of Criteria for Determining Response and Progression in Solid Tumor Oncology Study and Year Published CriteriaZubrod 1960WHO 1980SWOG 1992RECIST 2009 Response characteristics Measurement method Response criteria, % change Equivalent % volume change* Considers “clinical response” Not described Investigator consensus NA Yes Bidimensional Yes Bidimensional Yes Unidimensional No Progression characteristics Progression criteria, % change Equivalent % volume change* New lesions count as progression Two consecutive increases NA Yes Yes Yes Yes * This calculation assumes a spherical tumor mass. NA = not applicable. J Natl Cancer Inst.J Natl Cancer Inst Oct 17;104(20):

SARC 011 Multicenter trial of 115 patients with metastatic Ewing’s sarcoma treated with IGF1R antibody Anatomic/functional imaging per protocol: – CT/MR at baseline and at 6 week intervals… – FDG PET (day 0, 9, 84) Anatomic imaging reported by the treating physician Anatomic imaging reviewed centrally- Larry Schwartz FDG PET imaging reviewed- Richard Wahl

Purpose To describe which patients do poorest To contrast sarcoma expert oncologists vs radiology/nuclear medicine experts reading To contrast anatomic imaging vs FDG PET To explore new methodologies i.e. volumetrics

Secondary Analysis Three types of progression: 1) Presence of new lesions 2) Increase in size of existing lesions 3) Both of the above We contrasted the type of progression with overall survival Compared local and central interpretation of progression regarding overall survival

Local Interpretation of Week 6 Anatomic Imaging 104 patients (available for analysis) 93 pts with Week 6 anatomic imaging 39 pts with Non- Progressive disease (SD, CR, or PR) 54 pts with Progressive Disease Progression Based On: 1) Dimension criteria by WHO (N= 31) 2) Presence of new lesions (N=10) 3) Both dimension criteria and presence of new lesions (N=13) 11 pts without Week 6 anatomic imaging

Survival Using Local Interpretation

Central Interpretation of Week 6 Anatomic Imaging 99 patients (available for analysis) 80 pts with Week 6 anatomic imaging 29 pts with Non- Progressive disease (SD, CR, or PR) 51 pts with Progressive Disease Progression Based On: 1) Dimension criteria by WHO (N= 30) 2) Presence of new lesions (N=9) 3) Both dimension criteria and presence of new lesions (N=12) 19 pts without Week 6 anatomic imaging

Survival Using Central Interpretation

Median Survival (Days) Local Interpretation Central Interpretation CategoryNMedian Survival N Non- Progressive Disease Progression by Dimensions Progression by New Lesion Progression BOTH by Dimension Criteria and New Lesions No Week 6 Scan1129 P < 0.01

FDG PET Joo Hyun, Brandon S. Luber, Jeffrey P. Leal, Hao Wang, Vanessa Bolejack, Scott M. Schuetze, Lawrence H. Schwartz, Lee J.Helman, Laurence H. Baker, Richard L. Wahl

Conclusions Progression determined by increase in size and new lesions predicts for worse prognosis than either alone Central read non progression is predictive of longer survival than local read ( 517 days vs 329 days) Patients who did not have image at 6 weeks had worse survival (1 month), thus intent to treat analysis must be our standard FDG PET on day 9 is strong predictor of overall survival (ms in review)

Future Directions Compare RECIST and WHO criteria by central radiology Measure response and progression by volumetric analysis Compare individual patients that were nonprogression by CT/MR to those with partial metabolic response on FDG PET Compare two “expert” central reads of PET data